Download `DRAFT` Antiretroviral Treatment Guidelines

GUIDELINES FOR THE MANAGEMENT OF HIV & AIDS
IN HEALTH FACILITIES
National Department of Health
South Africa 2008
DRAFT 3
25 MARCH 2008
TABLE OF CONTENTS
FOREWORD .............................................................................................................................. 4
PREFACE ................................................................................................................................... 5
ABBREVIATIONS ............................................................................................................................ 6
SOME DEFINITIONS....................................................................................................................... 9
SECTION 1: HIGHLY ACTIVE ANTIRETROVIRAL TREATMENT (HAART) IN ADULTS ......... 10
A.
GOALS OF HAART .......................................................................................................... 10
B.
SELECTION CRITERIA .................................................................................................... 10
C.
ASSESSMENT FOR TREATMENT READINESS ............................................................ 11
D.
RECOMMENDED HAART REGIMENS IN ADULTS ....................................................... 13
1.
FIRST LINE HAART REGIMENS ..................................................................................... 13
2.
RECOMMENDED DOSING SCHEDULE AND COMBINATIONS FOR FIRST LINE
DRUG REGIMENS .......................................................................................................... 14
3.
APPROACH TO DRUG SUBSTITUTION IN FIRST LINE REGIMENS ........................... 15
4.
MONITORING DRUG BENEFITS AND TOXICITY FOR FIRST LINE HAART
REGIMENS ....................................................................................................................... 16
5.
CONSIDERATIONS FOR CHANGING HAART REGIMEN 1 .......................................... 17
6.
SECOND LINE HAART REGIMENS ............................................................................... 18
7.
RECOMMENDED DOSING SCHEDULE AND COMBINATIONS FOR .......................... 19
SECOND LINE DRUG REGIMENS ................................................................................ 19
8.
CLINICAL AND LABORATORY MONITORING FOR PATIENTS ON SECOND LINE
HAART REGIMENS.......................................................................................................... 20
9.
CLINICAL AND LABORATORY MONITORING FOR PATIENTS ON HAART ................ 22
10.
MANAGEMENT OF TREATMENT FAILURE AFTER THE SECOND LINE REGIMEN .. 25
11.
THE IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME RIS) ...................... 25
12.
MANAGEMENT OF PATIENTS PREVIOUSLY TREATED WITH ................................... 26
ANTIRETROVIRAL THERAPY (or non naïve patients) ................................................... 26
13.
HAART and PROPHYLAXIS OF OPPORTUNISTIC INFECTIONS................................. 26
14.
HAART and CONCOMITANT TUBERCULOSIS (TB) IN ADULTS .................................. 26
15.
PREGNANCY AND ANTIRETROVIRAL TREATMENT ................................................... 28
SECTION 2: MANAGEMENT OF HIV & AIDS INFECTION IN CHILDREN ............................... 33
1.
INDICATIONS FOR HAART IN CHILDREN ..................................................................... 33
2.
TREATMENT OF MOTHERS/ CAREGIVERS/OTHER FAMILY ..................................... 33
MEMBERS ........................................................................................................................ 33
3.
RECOMMENDED PAEDIATRIC HAART REGIMENS .................................................... 34
4.
SINGLE DRUG SUBSTITUTION OF STAVUDINE WITH ABACAVIR ............................ 35
SECTION 3: ADHERENCE TO HAART ....................................................................................... 36
1.
GENERAL CONSIDERATION .......................................................................................... 36
2.
ADHERENCE SUPPORT, ASSESSMENT AND MONITORING ..................................... 36
3.
DEFINITION OF ADHERENCE TO HAART..................................................................... 37
4.
ISSUES WHICH IMPACT ON ADHERENCE ................................................................... 37
5.
STRATEGIES TO PROMOTE ADHERENCE .................................................................. 38
6.
PRE-TREATMENT ADHERENCE PACKAGE ................................................................. 38
7.
ADHERENCE MEASURING TOOLS: (SEE ADULT PATIENT ADHERENCE RECORD
& MONITORING FORM - PARMF) .................................................................................. 39
8.
ADHERENCE PACKAGE FOR PATIENTS ON TREATMENT ........................................ 39
9.
STEP-UP ADHERENCE PACKAGE FOR PEOPLE WITH REDUCED ADHERENCE
OR VIROLOGICAL FAILURE ........................................................................................... 40
SECTION 4: DIAGNOSIS AND MANAGEMENT OF ADVERSE EVENTS ................................. 41
1.
PRINCIPLES OF MANAGING ADVERSE EVENTS ........................................................ 41
2.
IMPORTANT ADVERSE REACTIONS ............................................................................ 41
3.
SPECIFIC ADVERSE REACTIONS ................................................................................. 42
4.
DRUG INTERACTIONS.................................................................................................... 55
5.
SUBSTITUTES FOR INTOLERANCE IN ADULTS .......................................................... 56
6.
IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME (IRIS) ............................ 56
SECTION 5: MANAGEMENT OF OPPORTUNISTIC ................................................................... 58
DISEASES IN HIV POSITIVE ADULTS ........................................................................................ 58
1.
GENERAL PRINCIPLES .................................................................................................. 58
2
2.
HIV
COMPLICATIONS
ANTICIPATED
AT
VARIOUS
DEGREES
OF
IMMUNOSUPPRESSION ................................................................................................. 58
3.
RECOMMENDED PREVENTION OF OPPORTUNISTIC INFECTIONS IN HIV
POSITIVE ADULTS .......................................................................................................... 59
4.
MANAGEMENT OF OPPORTUNISTIC INFECTIONS IN HIV POSITIVE ADULTS ........ 65
SECTION 6: POST-EXPOSURE PROPHYLAXIS (PEP) ............................................................. 85
1.
PROPHYLAXIS AFTER ACCIDENTAL OCCUPATIONAL OR NON-OCCUPATIONAL
(INCLUDING SEXUAL ABUSE/RAPE) EXPOSURE TO HIV .......................................... 85
2.
PROPHYLAXIS AFTER OCCUPATIONAL (EXCLUDING RAPE) ................................... 85
3.
PROPHYLAXIS AFTER SEXUAL ASSAULT ................................................................... 86
APPENDIX 1: WHO clinical staging of HIV & AIDS for adults with confirmed HIV infection
(2006) ................................................................................................................................ 89
APPENDIX 2 : ADULT PATIENT ADHERENCE RECORD & MONITORING FORM [PARMF] ... 91
APPENDIX 3: TB PROPHYLAXIS ................................................................................................. 96
APPENDIX 4: EXCLUSION OF ACTIVE TB ................................................................................. 97
APPENDIX 5 ........................................................................................................................... 98
3
FOREWORD
Guided by the Operational Plan for the Comprehensive HIV & AIDS Care,
Management and Treatment Plan (The Comprehensive Plan) and the National Strategic
Plan for HIV & AIDS and STIs 2007-2011 (NSP), South Africa continues to intensify
the fight against HIV&AIDS. To date South Africans can access a comprehensive
package of care including Highly Active Antiretroviral Treatment (HAART) from
accredited Comprehensive Plan service points that are available in all health districts.
Much experience has been gained since we started implementing this Plan in April
2004.
The science of HIV treatment is evolving and treatment guidelines have to keep up to
date with developments. Updating the previous guidelines has taken into consideration
the need to minimise the risk of drug toxicity whilst optimizing treatment outcomes.
Ongoing treatment education and support are essential elements of the National HIV
and AIDS treatment programme. A comprehensive section on the management of
opportunistic diseases has been included, as well as a short reference to Paediatric HIV
& AIDS treatment
These guidelines are provided as a resource for use by all health care providers and
should be used in conjunction with other relevant guidelines. Regular use by health care
providers should ensure uniform, equitable, safe, sustainable and effective (principles
outlined in the Comprehensive Plan master document) management of patients with
HIV&AIDS.
The NSP 2007-2011 recommends regular reviews in keeping with emerging evidence
from active and passive surveillance, pharmacovigilance, monitoring and evaluation.
The Department of Health will strive to follow this recommendation, whilst supporting
research on the development of alternative and adjunctive approaches to treatment of
HIV & AIDS.
In order to enhance continuity and accelerate access, it is hoped that the private sector
and not-for-profit organisations civil society will as much as possible, follow these
guidelines.
DR MANTO TSHABALALA-MSIMANG
MINISTER OF HEALTH
DATE:
4
PREFACE
Almost four years into the implementation of the Comprehensive Plan with some
outstanding successes and formidable health systems challenges, large numbers of
people living with HIV and AIDS gained access to the various elements of the package
of treatment and care recommended in the Plan.
Establishing an adequate cadre of well-trained health care professionals, laboratory
technicians, pharmacists, doctors, social workers, nutritionists and community workers
is critical for the success of this programme.
Adherence to HAART is of paramount importance to reaping the long-term benefits
and avoiding development of resistance. Maximum adherence requires community
mobilization with patients supported by health care providers, family and the
community to participate and fully understand the benefit and limitations of HAART.
The National public health programme boasts one of the highest treatment retention
rates in the world. In order to optimise these outcomes and reduce the risks of drug
toxicity and resistance, it is imperative that this remarkable achievement is sustained.
Responding to the changes and development in the science of HAART these guidelines
aim to set the standard for the use of HAART and the management of opportunistic
diseases and AIDS in South Africa.
Providing the best possible and safest care for those with HIV&AIDS in South Africa is
possible. All health care workers in the public and private sector are urged to
familiarize themselves with these guidelines so that we, together, provide the best
possible and safest care for those with HIV&AIDS.
MR TD MSELEKU
DIRECTOR-GENERAL
DEPARTMENT OF HEALTH
5
ABBREVIATIONS
AIDS
Acquired immune deficiency syndrome
ARV
Antiretroviral
AZT
Zidovudine (anti-retroviral drug)
CD4
CD4 cell or T4 ‘helper’ lymphocyte
CSF
Cerebrospinal fluid
CM
Cryptococcal meningitis
CMV
Cytomegalovirus infection
CT scan
Computerised Tomography Scan
DOT
Directly observed treatment
E
Ethambutol
EBV
Epstein-Barr virus
ELISA (HIV)
Enzyme-linked immunosorbent assay – A type of HIV antibody laboratory test
EPTB
Extrapulmonary tuberculosis
FBC
Full blood count
FTA
Fluorescent treponemal antigen – specific laboratory test for syphilis
GI
Gastro-intestinal GUD Genital ulcer disease
H Isoniazid
HAD HIV Associated Dementia
HAART
Highly Active Antiretroviral Therapy
HHV8
Human herpes virus 8 HIV Human immunodeficiency virus
HPV
Human papillomavirus
HSV
Herpes simplex virus
INH
Isoniazid
KS
Kaposi’s sarcoma
LDH
Lactose dehydrogenase
MAC
Mycobacterium avium complex
6
MDR TB
Multi-drug resistant tuberculosis
NHL
Non Hodgkin’s lymphoma
NNRTI
Non-nucleoside reverse transcriptase inhibitor (anti-retroviral drug)
NRTI
Nucleoside reverse transcriptase inhibitor (anti-retroviral drug)
OHL
Oral hairy leukoplakia
P24
HIV antigen test
PAP smear
Papanicolaou test
PCP
Pneumocystis jiroveci pneumonia
PCR
Polymerase chain reaction (a laboratory HIV detection test)
PGL
Persistent generalised lymphadenopathy
PI
Protease inhibitor (anti-retroviral drug)
PID
Pelvic inflammatory disease
PML
Progressive multifocal leukoencephalopathy
PTB
Pulmonary tuberculosis
PLWHA
Person living with HIV/AIDS
QID
6 hourly
R
Rifampicin
RPR
Rapid plasma reagin – a non specific test for syphilis
S
Streptomycin
SIL
Squamous intraepithelial lesion
STD
Sexually transmitted disease
T4
Helper lymphocyte
TCA
Trichloroacetic acid
TMP-SMX
Trimethoprim/sulphamethoxazole also known as Cotrimoxazole or Bactrim ® or
Septran ®
TE
Toxoplasma encephalitis
TB
Tuberculosis
7
TBM
Tuberculous meningitis
TID
8 hourly - 3 times a day
TPHA
Treponema pallidum haemagglutination assay – a specific laboratory test for
syphilis
URTI
Upper respiratory tract infection
VZV
Varicella-Zoster Virus
VZIG
Varicella-Zoster Immune Globulin
VDRL
Venereal diseases research laboratory (a non-specific test for syphilis)
VL (HIV)
HIV Viral load
WHO
World Health Organization
Z
Pyrazinamide
ZAP
Zoster-associated pain
ZDV
Zidovudine (anti-retroviral)
8
SOME DEFINITIONS
Treatment failure results mainly from failure to suppress viral replication. The most
reliable tool to measure treatment failure is the viral load. This should be suppressed
(<400 copies/ml) within 6 months of starting the first line regimen.
Virological failure is defined as failure to suppress, or if previously suppressed viral
load rises significantly (see table 6). The CD4 count typically increases by about 100
cells / mm3 in the twelve months and by about 50 in each subsequent year, but this
increase is highly variable. Treatment failure should not be defined by CD4 count
criteria as a proportion of patients with a suppressed viral load will fail to increase their
CD4 counts, and changing therapy will not improve this.
On the other hand, a large proportion of patients will have a good increase in their CD4
cell count despite incomplete viral load suppression. In this situation resistance to
antiretroviral drugs will occur.
Clinical failure is progression of disease with the development of opportunistic
diseases. This may occur during the first 3 months of HAART before the CD4 count
has increased significantly. At this point, it is not necessary to switch to another
regimen. Even if a new opportunistic disease erupts, the treatment regimen should only
be switched if this is accompanied by virological failure.
Step-up adherence package
Steps taken to promote adherence to ideal adherence of taking more than 95% of their
doses when adherence assessment is <80% at any visit, with or without viral or clinical
failure. to ensure
Down-referral
Referral of patients that are responding well to HAART for 6 months after initiation to
a lower level of care within the same service point.
Initiation site
These are sites where patients are commenced on antiretroviral therapy. This will
largely be at PHC sites in the future, but also includes secondary- and tertiary- level
facilities. Patients are refered , once stabilized on HAART, to maintenance
sites.Initiation site operates as referral site for patients with clinical problems that are
referred from maintenance sites (‘up referral’).
Maintenance site
Site where stable patients on antiretroviral therapy, as well as those not yet needing
HAART are monitored; usually based at PHC or CHC facility. Refers patients with
clinical problems, which cannot be managed at the maintenance site, to initiation sites
(tertiary- or secondary-level health care facilities).
9
SECTION 1: HIGHLY ACTIVE ANTIRETROVIRAL
TREATMENT (HAART) IN ADULTS
A.
GOALS OF HAART
1.
The primary goal of HAART is to decrease HIV&AIDS-related morbidity and
mortality
 The patient should experience fewer HIV-related illnesses.
 The patient’s CD4 count should rise and remain above the baseline count.
 The patient’s viral load should become undetectable (<400 copies /ml), and
remain undetectable on HAART.
2.
The secondary goal is to decrease the rate of new HIV infections through:
 Reducing the risk of HIV transmission from mother to child.
B. SELECTION CRITERIA
1.
Medical indications
o CD4 count ≤ 250 cells/mm3 irrespective of WHO Clinical stage
OR
WHO Clinical Stage IV irrespective of CD4 count (with the exception of
tuberculosis, when the CD4 criterion of ≤ 250 cell / mm3 should be applied)
OR
o Other severe HIV-related conditions or co-morbidity. This group of
conditions requires specialist diagnosis and recommendation. Examples of
conditions in this category include:
 Immune Thrombocytopenic Purpura and Thrombotic
Thrombocytopenic Purpura
 Severe manifestations of the diffuse infiltrative lymphocytic
syndrome (e.g. lymphocytic interstitial pneumonitis, polymyositis)
 MDR or XDR tuberculosis
 Severe hidradenitis suppurativa
 Patients being treated for non-HIV-related metastatic or
disseminated malignancies
2.
Psychosocial considerations (not exclusion criteria):



Demonstrated reliability, i.e. patient has attended three or more scheduled
visits to an HIV clinic.
No active alcohol or other substance abuse.
No untreated active depression.
1 Latest WHO staging includes more conditions, e.g. HIV cardiomyopathy and
HIVAN, see appendix 1.
10



Disclosure: it is strongly recommended that patients have disclosed their
HIV status to at least one friend or family member OR have joined a support
group.
o If possible the patient should identify a treatment supporter who
should also receive information and be educated on HAART
Insight: patients need to have accepted their HIV positive status. They need
to have insight into HIV infection, the role of HAART and the
consequences of non-adherence before commencing therapy.
Patients should be able to attend the antiretroviral treatment facility on a
regular basis or have access to services that are able to maintain the
treatment chain. Where access is problematic for patients due to distances
for example, clinic staff need to ensure that arrangements be made for these
patients to facilitate access to care.
N.B. Patient selection: The final decision to initiate HAART should be taken by a
multi-disciplinary team (community adherence supporters, counsellors, nurses,
pharmacists, doctors, nutritionists and social workers) at the treatment point once the
patient has accepted the treatment option. The clinician in charge will initiate treatment.
Table 1: Summary of criteria for HAART initiation in adults
CD4 ≤250 cells/ mm3 irrespective of WHO Clinical stage
OR
WHO Clinical Stage IV, irrespective of CD4 count
OR
Other severe HIV-related conditions or co-morbidity (specialist-initiated)
AND
Patient expresses willingness and readiness to take ART
Note: see WHO staging tables in Appendix 1
Except tubrculosis, when the CD4 criterion of ≤ 250 cells / mm3 should be applied
C.
ASSESSMENT FOR TREATMENT READINESS
1.
HAART Readiness Assessment and Preparation
The first 2 – 4 weeks:
1.1
First visit:
 Confirm the selection criteria: clinical and laboratory
 Identify those with TB and pregnant women.
 Perform the following baseline investigations:
o FBC
o ALT
o Creatinine
o Hepatitis B surface antigen (FOR FURTHER DISCUSSION)
11








1.2
Take comprehensive history & examine the patient
Treat any opportunistic infection.
Patients must meet with members of the multi-disciplinary team
individually or as a group for information and one on one counselor.
Treatment adherence counselor will discuss issues around the need for
treatment, the rationale for adherence and strategies that will overcome
barriers to adherence with the patient
The patient advocate or community adherence supporter will do a basic
psychosocial assessment to document the patient’s social issues and current
psychological state, focusing on factors which might have an impact on the
patient’s adherence. This is to evaluate issues that might impact on long
term adherence. In some cases, it may be necessary to do a home visit.
A 28-day supply of co-trimoxazole is given to the patient as part of long
term prophylaxis against PCP and other bacterial infections as well as a
measure of their adherence.
The patient is given a set of dates to return for more adherence counselling,
training and education.
Correctness of the contact details
Second visit
 Clinical assessment and revision of results
 Information and education session
 Adherence check using co-trimoxazole pill count
This should not take more than 4 weeks. Patients with CD4 counts of <50
should be considered for a shorter induction period. In such cases, longer term
ongoing education on treatment should be given during the course of therapy.
1.3
Assessing patient readiness
HAART readiness criteria may include the following:
 Patient’s acceptance of their HIV status and the need for HAART
 Medical and psychosocial criteria met
 Absence of severe medical contra-indication (active disease that is not
stabilized, including depression)
 Understanding of the importance of adherence and attendance to all
scheduled pre-treatment visits and educational sessions
Patients who, on nonmedical grounds, do not meet the treatment readiness
criteria should be referred for further counselling and education.
2.
HAART commencement visit
Except for post-exposure prophylaxis, HAART is not an emergency treatment.
The pharmacist should:
 Re-assess patient’s readiness.
 Do a co-trimoxazole pill count.
 Provide detailed description and dosing of the antiretroviral drugs.
Clinicians should:
 Check baseline laboratory investigations:
 Elevated ALT Results
1. If the baseline ALT is elevated, repeat this to confirm the result.
12






D.
2. If ALT is less than two and a half times the upper limit of normal,
ART can be commenced and ALT monitored monthly for three
months.
3. Patients with ALT higher than this should be referred for specialist
opinion.
Elevated Creatinine levels
1. All patients with elevated creatinine require assessment by a doctor
trained in HAART before commencing treatment.
2. Tenofovir is contraindicated if GFR <50ml/min or with a creatinine
clearance of < 50ml/min.
3. Dose modification for AZT, d4T, 3TC and ddI is necessary with
elevated creatinine, and
Hepatitis B surface Ag positive (For further discussion)
1. If the hepatitis B surface antigen is positive, the patient should be
commenced on Tenofovir and 3TC
2. Note that these antiretrovirals must not be stopped, even if the
patient fails first line therapy, as severe flares of hepatitis B may
occur.
Perform a Pap smear for all women if not done in the last twelve months
Provide detailed description and dosing of the antiretroviral drugs.
Ensure that dosing instructions are clearly written on the container with a
permanent marker.
Discuss further information and adherence issues with the patient and
his/her counselor or advocate.
RECOMMENDED HAART REGIMENS IN ADULTS
Antiretroviral drugs are often used in triple therapy combinations in order to enhance
efficacy and to prevent or delay the emergence of drug resistance. Selection of a
combination should be individualized.
1. FIRST LINE HAART REGIMENS
Regimen 1a : Stavudine/Lamivudine/ Efivarenz
Unless it is contra-indicated, all patients should be commenced on Regimen 1a:
Contraindications to the use of Regimen 1a:
 Women of child-bearing potential, who are unable to guarantee reliable
contraception while on HAART.
 First trimester of pregnancy
 Obese women (BMI > 28)
 Patients with positive Hepatitis B surface Ag
 Patients on psycho-active drugs
13
Regimen 1b: Stavudine/Lamivudine/ Nevirapine
Indications:
Recommended for women of child-bearing potential who are unable to guarantee
reliable contraception while on HAART as well as women who become pregnant on
regimen 1a.
Contraindications to the use of Nevirapine
 Women with CD4 cell count >250cells/ mm3
 Men with a CD4 cell count > 400 cells/ mm3
 Grade 3 or more of ALT elevation (>5 times upper limit of normal)
 Avoid using with Rifampicin during the treatment of TB
 Hepatitis B surface Ag positive
 Grade 3 or 4 rash
Contraindications to the use of Stavudine
 Obese women (BMI > 28)
 Patients with symptoms of pre-existing neuropathy
 Previous history of severe d4T toxicity
Regimen 1c: Zidovudine/Lamivudine/Efivarenz
Indications:
Recommended for obese women with a Body Mass Index > 28.
Contraindications to the use of Zidovudine
 Hb below 6.5g / dl or Neutrophil count below 0.5 X 10 9 / l especially if also on
cotrimoxazole
Regimen 1d: Tenofovir/Lamivudine/Efivarenz
Indications:
Recommended for patients who experience severe d4T toxicity and those with a
positive Hepatitis B surface Ag serology result.
Contraindications to the use of Tenofovir
 Contraindicated if GFR <50ml/min or with a creatinine clearance of <
50ml/min.
2. RECOMMENDED DOSING SCHEDULE AND COMBINATIONS FOR
FIRST LINE DRUG REGIMENS
Regimen 1a
Stavudine (d4T) 30 mg 12 hourly (this dose should be given regardless of weight or
BMI)
AND
Lamivudine (3TC) 300mg, daily or Lamivudine 150mg 12 hourly
AND
Efavirenz (EFV) 600 mg at night (400 mg if <40 kg)
14
Regimen 1b
Stavudine (d4T) 30 mg 12 hourly (this dose should be given regardless of weight or
BMI)
AND
Lamivudine (3TC) 300mg, daily or Lamivudine 150mg 12 hourly
AND
Nevirapine 200 mg daily for the first 2 weeks, increasing to 200 mg every 12 hours
after this( unless there are contraindications)
Regimen 1c
Zidovudine(AZT) 300mg 12hrly
AND
Lamivudine (3TC) 300mg, daily or Lamivudine 150mg 12 hourly
AND
Efavirenz (EFV) 600 mg at night (400 mg if <40 kg)
Regimen 1d
Tenofovir (TDF) 300mg daily
AND
Lamivudine (3TC) 300mg daily, or Lamivudine 150mg 12 hourly
AND
Efavirenz 600 mg at night (or 400 mg if <40 kg) OR nevirapine 200 mg daily for the
first 2 weeks, increasing to 200 mg every 12 hours after this.
3. APPROACH TO DRUG SUBSTITUTION IN FIRST LINE REGIMENS
The management of patients who have previously been HAART and any switching of
drugs needs to be discussed with a HIV clinician.
.
Table 2: Summary of considerations for substitutions in first line therapy.
Clinical indication
Peripheral neuropathy
Substitution
AZT for d4T
Obese women (body mass AZT for d4T
index >28)
Liver disease
EFV for NVP
Hepatitis B surface antigen TDF for d4T
positive
Psychosis
depression
or
untreated NVP for EFV
Known toxicity and benefits
Stavudine
causes
peripheral
neuropathy
Stavudine is higher risk for
symptomatic hyperlactataemia/lactic
acidosis
Nevirapine is higher risk for hepatitis
Tenofovir and lamivudine are active
against hepatitis B and HIV – the
combination protects against hepatitis
B resistance. Specialist initiated
Efavirenz has neuropsychiatric
side effects
15
Symptomatic
hyperlactataemia
Lipoatrophy
TDF for d4T
Tenofovir has a low potential for
mitochondrial toxicity – see Section 4
Tenofovir has a low potential for
mitochondrial toxicity – see Section 4
TDF for d4T
4. MONITORING DRUG BENEFITS AND TOXICITY FOR FIRST LINE
HAART REGIMENS
Table 3: Routine monitoring for HAART First line Regimens:
Regimen
Drugs
Monitoring
tests
Frequency
1a
d4T / 3TC / EFV
CD4

Staging, 6
monthly
VL

@3 months,
then 6
monthly
ALT

Baseline, week
2, 4, 8,12
thereafter
6-monthly
1b
d4T / 3TC / NVP
CD4

VL

Staging, 6
monthly
@3 month
then 6 monthly
ALT

1c
AZT / 3TC / NVP
CD4
VL
ALT
Baseline, week
2, 4, 8,12
thereafter
6-monthly
 Staging,
monthly, 3
monthly,
6monthly
 @3 month
then 6 monthly
 Baseline, week
2, 4, 8,12
thereafter
6-monthly
16
Table 3:
Regimen
Routine monitoring
Drugs
for HAART
Monitoring
tests
First
line Regimens:
Frequency
1d
TDF / 3TC / EFV
CD4

VL

Cr

Staging, 6
monthly
@ 3 month
then 6 monthly
Baseline,
monthly X3 , 6
months, 6
monthly
5. CONSIDERATIONS FOR CHANGING HAART REGIMEN 1
The management of patients who have previously been HAART and any switching of
drugs needs to be discussed with a HIV clinician.
The commonest reason for the virological failure is poor adherence. Attempts should
always be made to improve adherence before switching regimens is considered.
Table 4: Viral load monitoring:
Viral load (VL)
Response
<400 copies/ml



6-monthly viral load monitoring
Routine adherence support.
Table 4: Viral load monitoring:
Viral load (VL)
Response
17
400-1000 copies/ml
Repeat viral load in 6 months
 Begin step-up adherence package.
Review at next 6-month viral load
check.
 If <400, return to routine 6-monthly
monitoring and adherence support.
 If still between 400 and 1 000,
continue with step-up adherence
package. Repeat viral load at 6
months.
 If >1 000, despite stepped-up
adherence support, switch to secondline therapy only if adherence is
>80%.
>1 000 copies/ml
Repeat viral load in 3 months
 Begin step-up adherence package.
Review at next 6-month viral load
check.
 If <400, return to routine, 6-monthly
monitoring and adherence support.
 If between 400 and 1 000, continue
with step-up adherence package.
Repeat viral load again after a further
6 months.
 If >1 000, despite stepped up
adherence support, switch to secondline therapy only if adherence is
>80%.
6. SECOND LINE HAART REGIMENS
Indications for switching to second line regimen:
Second line regimens should only be considered for patients who have experienced
virological failure in spite of a good drug adherence record. Specifically, the following
patients should be considered for second line regimens:
 Failure to suppress viral load to (<400 copies/ml) within 6 months of starting
any first line regimen.
 If viral load >1 000copies/ml despite stepped up adherence support
Regimen 2a: Zidovudine/Didanosine/Lopinavir/ritonavir
All patients with virological failure on regimen 1 should be switched to regimen 2a
unless contraindicated.
Obese women (BMI > 28) initiated on AZT as well as pregnant women should be
continued with in the second line regimen.
18
Regimen 2b: Tenofovir/Lamivudine/Lopinavir/ritonavir
Recommended for patients who have developed sever toxicity to d4T and with
virological failure on Regimen 1 should be switched to regimen 2b.
N.B. Didanosine must never be combined with Tenofovir!
N.B Patients who are hepatitis B surface antigen positive must not stop Tenofovir
and 3TC as severe flares of hepatitis B may occur. Patients in this situation
should be discussed with an HIV clincician.
Regimen 2c: Zidovudine/Didanosine/Lopinavir/3Xr
Recommended for pregnant women and patients who are on antiTB drugs containing
Rifampicin.
7. RECOMMENDED DOSING SCHEDULE AND COMBINATIONS FOR
SECOND LINE DRUG REGIMENS
Regimen 2a
 Zidovudine (AZT) 300 mg every 12 hours
AND
 Didanosine (ddI) 400mg once a day (250mg daily if <60kg), taken alone,
dissolved in water, on an empty stomach
AND
 Lopinavir/ritonavir (LPV/r) 400mg/100 mg every 12 hours
N.B Didanosine must be taken alone, on an empty stomach, at least an hour
before, or at least 2 hours after a meal. Less than 50% is absorbed if taken
immediately after a meal. Tablets should be dissolved in at least 30 ml of water.
No other liquids may be used to dissolve the tablets. There is no need to dissolve
the enteric-coated version.
Regimen 2b
 Tenofovir 300mg daily


AND
Lamivudine (3TC) 300mg daily OR Lamivudine 150mg 12 hourly
AND
Lopinavir/ritonavir (LPV/r) 400mg/100 mg every 12 hours
Regimen 2c
 Zidovudine (AZT) 300 mg every 12 hours
AND
 Didanosine (ddI) 400mg once a day (250mg daily if <60kg), taken alone,
dissolved in water, on an empty stomach
AND
 Lopinavir/ritonavir (LPV/r) 400mg/300 mg every 12 hours
19
8. CLINICAL AND LABORATORY MONITORING FOR PATIENTS ON
SECOND LINE HAART REGIMENS



The patient's response to therapy will be monitored by CD4 count and viral
load.
Assessment will be after 6 months.
At each visit the patient's viral load will place them into one of three categories.
Their category will determine further outcome and programme response (See
table 4)
8.1 Scheduled visits
Patients starting HAART Regimen 2 need to be seen by a doctor at least once a month
for first 3 months. Thereafter the visits should be once in six months or as required.
Drugs need to be collected every month.
Table 5: Summary of adult HAART Regimen 2 and routine monitoring
Regimen
Drugs
2a
AZT / ddI /
lopinavir / ritonavir
Monitoring
tests
Frequency

CD4


FBC


Fasting
cholesterol and
triglyceride


Fasting glucose

CD4

Creatinine

2b
TDF/3TC/lopinavir/ritonav
ir



Staging, 6monthly

Baseline, monthly
X3 , 6 months, 6
monthly

Baseline, 3
months and
thereafter every
12 months

Baseline, 3
months and
thereafter every
12 months
Fasting
cholesterol and
triglyceride
Fasting glucose
Staging, 6monthly
Baseline, then
monthly for 3
months, then at 6
months
Baseline, 3
months and
thereafter every
12 months
Baseline, 3
months and
thereafter every
12 months
20
Table 5: Summary of adult HAART Regimen 2 and routine monitoring
Regimen
Drugs
2c
AZT / ddI / 3X
lopinavir /ritonavir
Monitoring
tests
Frequency

CD4

Staging, 6monthly

Fasting
cholesterol and
triglyceride

Staging, 6monthly
Baseline, 3
months and
thereafter
every 12
months

Fasting
glucose

Staging, 6monthly
Baseline, 3
months and
thereafter
every 12
months
8.2 Unscheduled visits
 Clinical judgment will be used to assess the need for additional safety
investigations depending on the presenting adverse event.
 No extra CD4 counts or viral loads should be done, except when at six
months after a previous viral load >5 000 copies/ml.
Table 6: Recommended adult HAART regimens in summary:
Regimen
Drugs
d4T/3TC/EFV
1a
1b
1c
1d
1e
2a
2b
2c
d4T/3TC/NVP
AZT /3TC/EFV (obese women)
TDF/3TC/EFV (severe d4T toxicity)
D4T / 3TC / lopinavir / ritonavir(raised ALT and / or
Hep sAg positive in pregnancy)
AZT/ddI/lopinavir/ritonavir
TDF/3TC/lopinavir/ritonavir (severe d4T toxicity and
virological failure on regimen 1)
AZT/ddI/lopinavir/3X ritonavir (on antiTB drugs)
21
9. CLINICAL AND LABORATORY MONITORING FOR PATIENTS ON
HAART
9.1 Scheduled visits
Patients should attend clinics monthly to collect medication. The pharmacy must play a
role in adherence counselling. Patients should be seen by the professional nurse who
should assess drug tolerance, adverse events and adherence. Ideally pills should be
counted by the clinic nurse or doctor or pharmacist or pharmacy assistant or the
counsellor at each scheduled visit.
Patients that are on nevirapine should, in addition to the regular schedule, be seen two
weeks after initiation of HAART in order to monitor:
 for adverse events
 ALT levels
 ensure the correct dosing
9.2 Down referrals
All patients should be seen monthly for the first 6 months. Patients that are well and
have responded well to HAART can be considered for referral to a lower level of care
within the same service point. Patients who are not well, should be seen more
frequently as determined by the doctor or nurse responsible for care.
The referral programme will provide much needed support to all staff members
working at both the initiation and maintenance sites, and ultimately strengthen the
health care services.
9.2.1 Indications for “down-referral”
9.2.1.1 Adult ‘down-referral’ Criteria from initiation to maintenance site:
a)
b)
c)
d)
e)
f)
Clinically stable (as determined by the clinician / s that care for the patient).
Patient has completed at least six months of HAART.
No current serious side effects and adverse drug reactions.
Undetectable viral load (less than 400 RNA copies per mL).
No serious co-morbidities (e.g. kidney transplant, lymphoma, etc).
Patients with significant HIV-related irreversible side effects (e.g. peripheral
neuropathy, paraplegia, dementia, etc) can be referred to the maintenance site if
the side effect is adequately controlled or condition optimized.
9.2.1.2 Criteria for referring children receiving HAART from initiation to
maintenance sites:
a. The care-giver should fully understand and agree to the referral process.
b. Clinically stable (WHO Stage I/ II; also stable WHO Stage III/ IV at the discretion of
the clinician/s taking care of the patient).
c. Completed at least 6 months of HAART.
d. No current serious side effects and adverse drug reactions.
e. Undetectable viral load (less than 400 RNA copies per mL).
22
f. No serious co-morbidity.
g. Other chronic medications should be available at the maintenance site.
h. Staff at the initiation site must fully discuss the medical and psychosocial status of
the referred child with health workers at the maintenance site.
Table 7 shows the time events schedule for patients eligible for HAART
CD4 counts are done 6-monthly while patients are on Regimen 1.
Viral loads are done at 3months and at 6 months after initiation and 6-monthly
thereafter while patients are on Regimen 1.
23
Table 7: Time events schedule
Assessment
Screening
week 4
Commen
ce ART
week 0
Education/
Therapeutic
Counsellor
visit
Treatment
Readiness
assessment
History
Physical exam
Complete
registers
C
C
Baseline
investigation
for Regimen 1
Mantoux
(Tuberculin
test,
Pregnancy
test
FBC,
Safety bloods
for Regimen
1a with d4T
Safety bloods
Regimen 1b
with NVP
Baseline
investigation
for Regimen
1b
Safety bloods
Regimen 1c
with AZT
Safety bloods
Regimen 1d
with TDF
Safety bloods
Regimen 2a
Week
2
Week
4
Week
8
Week
12
Monthl
y
3
Mont
hly
C
C
C
C
C
D
D
D
N
D
N
Na
Na
Na
Cr
Cr
Nb
Nb
D
D
N
FBC, ALT,
HepB sAg
D
D
N
Na
Na
D
N
Na
Papsmear
FBC
FBC,
Cr
FBC,
Nb
Fasting
cholesterol&
triglyceride
Nb
Nb
Cr
FBC, Cr
Fasting
cholesterol&
triglyceride
Fasting
glucose
Cr
Cr
Nb
Nb
Nb
Nb
Viral load
CD4 count
Adverse events
6
Mo
nth
ly
Whole
team
Fasting
glucose
Safety bloods
Regimen 2b
With TDF
6
mont
h
Nb
Nb
Nb Cr
Nb Cr
Cr
Cr
D
N
N/P
D/P
D/P
D/P
N/P
Nb
Cr
D
N
Adherence
check
TC/N
P/N
TC /
D
P/N
TC /
D
P/N
TC /
D
P/N
TC /
D
P/N
TC / D
P/N
TC / D
P /
N
TC
/D
C = counsellor; D = doctor; N = nurse; TC = therapeutic counsellor; PA = patient
advocate; P = pharmacist
For information on a, b, c, see below
a.For patients on nevirapine, ALT will be taken at baseline, Week 2, 4 and 8, 12 then 6
monthly.
b.For patients on HAART Regimen 2, FBC will be done monthly for the first 3 months,
then 6 monthly. Fasting cholesterol, triglycerides and fasting glucose will be done as in
Table 6.
c.
Calculate monthly adherence = (tablets dispensed – tablets returned)/ (tablets
prescribed), e.g. (30 – 5)/28 = 25/28 = 0.9 (90%).
10. MANAGEMENT OF TREATMENT FAILURE AFTER THE SECOND LINE
REGIMEN
Salvage therapy is currently not an available and affordable option in the public health
sector. There may be some benefit in continuing on Regimen 2 if an informed patient so
wishes. The ethical principle of “first-do-no-harm” should be upheld in scuh cases.
(Gary and Prakash to comment on this one to).
11. THE IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME RIS)
IRIS occurs when improving immune function unmasks a previously occult
opportunistic infection which subsequently presents with an unusually aggressive
inflammatory presentation, or causes paradoxical deterioration of an existing
opportunistic disease. Patients with advanced HIV disease, particularly those with a CD4
count < 50 cells mm3, may become ill with an immune reconstitution inflammatory
syndrome (IRIS) during the first 3 months of HAART. Tuberculosis is the commonest
presenting IRIS reaction in South Africa. About a third of patients starting HAART
when on treatment for tuberculosis will experience recurrence of their TB
symptoms/signs or worsening or new manifestations. The commonest of these
presentation is with enlarging lymph nodes, often with extensive caseous necrosis. It is
important to exclude multi-drug resistance in these cases. Also, opportunistic infections
may present in atypical ways during this phase of immune reconstitution. Patients need
to be referred to an experienced HIV clinician for advice regarding investigation and
management.
IRIS is not indicative of drug failure or drug side effects. It is not a reason to stop
HAART, or to change the highly active antiretroviral regimen.
25
12. MANAGEMENT OF PATIENTS PREVIOUSLY TREATED WITH
ANTIRETROVIRAL THERAPY (or non naïve patients)
Patients who have been treated with HAART in the past should be discussed with an
HIV clinician before any treatment regimen is commenced.
 Those patients controlled on their antiretroviral medication should continue on
their treatment or swap to the appropriate treatment protocol.
 Those patients who stopped for several reasons, but who were responding well,
could recommence therapy and be monitored as per schedule.
Those patients who have failed a previous regimen should ideally be started on
appropriate drugs they have not been exposed to before.
13. HAART and PROPHYLAXIS OF OPPORTUNISTIC INFECTIONS



Co-trimoxazole prophylaxis must be continued in all patients on HAART until
the CD4 count is >200 cells/mm3. It should be recommenced if the CD4 count
drops to ≤ 200 cells/ mm3 when therapy fails.
Patients who have had cryptococcal meningitis must continue taking Fluconazole
prophylaxis until the CD4 count is >250 cells/ mm3.
Patients on Isoniazid preventive therapy (IPT) who start HAART should
complete their 6 month IPT regimen (together with pyridoxine to reduce the risk
of developing peripheral neuropathy).
14. HAART and CONCOMITANT TUBERCULOSIS (TB) IN ADULTS
Tuberculosis is a common co-morbid illness with HIV. If an HIVpositive patient has
symptoms suggestive of TB, 2 sputum specimens should be collected for 2 smears and a
TB culture. It is very important to investigate patients for tuberculosis before starting
HAART:
Suspect TB if 2 or more of the following are present:
Observed weight loss of ≥ 5 kg over the past 4 weeks
Cough >2 weeks
Night sweats >2 weeks
Fever >2 weeks
Lethargy or listlessness
If TB is diagnosed, there are two scenarios to consider:
14.1 The patient that develops tuberculosis while on HAART
HAART should be continued throughout TB treatment, with changes to HAART
regimens (for patients on Rifampicin containing TB treatment) and monitoring as
follows:
 HAART Regimen 1: A change to Efavirenz is recommended for patients on
Nevirapine wherever possible. If this is not possible (e.g. intolerant of efavirenz
26

or significant risk of falling pregnant), nevirapine may be continued in selected
cases, with monthly ALT monitoring.
HAART Regimen 2: Lopinavir/ritonavir is recommended as in Regimen 2c.
This should be accompanied with monthly ALT monitoring.
14.2 The patient that presents with TB before commencing HAART

If the patient has no history of WHO Stage IV illness, and has a CD4 count > 250
cells/ mm3, HAART is not indicated.
o The need for HAART should be reassessed on completion of TB
treatment.
 If the patient has a history of WHO Stage IV illness (other than TB), and/or a
CD4 count ≤ 250 cells/mm3, complete 2 to 8 weeks of TB therapy before
commencing HAART.
o Patients in this group should be started on first-line therapy – Regimen
1a.
Nevirapine should generally be avoided because of the associated negative drug-drug
interactions.
Table 8: Common shared side-effects of TB and HAART
Side effects
Nausea
HAART
Tuberculosis treatment
didanosine,
zidovudine, pyrazinamide
protease inhibitors
Hepatitis
nevirapine, efavirenz
rifampicin,
pyrazinamide
Peripheral neuropathy
stavudine, didanosine
isoniazid
Rash
nevirapine, efavirenz
rifampicin,
pyrazinamide
14.3
isoniazid,
isoniazid,
Recommended dosing schedule and combinations in patients with
commitant TB disease
Patients should be counselled about the following:
 Treatment for TB together with HAART involves taking a large number of
tablets.
 When HAART is commenced, the patient’s TB symptoms may temporarily
worsen as part of immune reconstitution.
Scenario 1: TB develops while on HAART
Continue HAART throughout TB treatment. Patients on first-line therapy containing
nevirapine should generally be swapped to efavirenz as follows:
First-line therapy:
27



Stavudine 30 mg every 12 hours
AND
Lamivudine 300mg or 2X 150mg daily or 150 mg every 12 hours
AND
Efavirenz 600 mg at night
Second-line therapy:



Zidovudine (AZT) 300 mg every 12 hours
AND
Didanosine (ddI) 400 mg once a day (250 mg daily if <60 kg) on an
empty stomach
AND
Lopinavir/ritonavir 400/200 mg every 12 hours
Scenario 2: TB disease before HAART is started:
a) CD4 cell count >250 cells/mm3 (and no other HIV-related symptoms):
Start TB treatment. Assess the need for HAART after completing TB therapy, using
CD4 and clinical criteria.
b) CD4 cell count <250 cells/mm3:
Delay ART until after 2-months intensive phase of TB therapy.
Then start on regimen 1a as below:
First-line therapy:
 Stavudine 30 mg 12 hourly
AND
 Lamivudine 300mg or 2X 150mg daily or150 mg every 12 hours
AND
 Efavirenz 600 mg at night
c) CD4 cell count of <50 cells/mm3 or other serious HIV illness:
Introduce ART as soon as the patient is stabilized on TB therapy (no less than 2 weeks
between starting TB therapy and starting HAART).
N.B In these patients, intensive education, counselling and support is a critical predictor
of adgerence and treatment outcomes.
15. PREGNANCY AND ANTIRETROVIRAL TREATMENT
15.1 PRINCIPLES OF MANAGEMENT


The current SA guidelines for HAART recommend initiating HAART in
patients with WHO clinical stage 4 or CD4 ≤ 250 cells/mm3.
A woman who becomes pregnant whilst on HAART should have EFV
switched to NVP in the first trimester. After the first trimester there is no
need for the switch. Adverse event monitoring (including foetal anomaly
scans) is critical in all cases.
28

Nevirapine-based regimen is not recommended in women with a CD4 cell
count >250cells/ mm3 because of the increased risk of toxicity.
15.2 COUNSELLING AND TESTING FOR PREGNANT WOMEN





All pregnant women should be offered HIV testing at their initial booking
visit.(i.e. all should be pre-test counselled and then offered an HIV test).
Finger pricks should be performed at the same time as routine antenatal
booking blood specimens are taken.
Women who test HIV positive on the rapid test should have a CD4 count
taken on the same day. The result of this CD4 should be checked within a
week and documented.
Women who decline an HIV test should, at every antenatal visit, be
encouraged to take the test.
Women who tested HIV negative in pregnancy should be offered a repeat
HIV test at 34 weeks gestation.
15.3 HAART FOR PREGNANT WOMEN
Women with medical indications for HAART should be intiated on treatment regardless
of the gestational age of the pregnancy. In cases where this is not possible, the PMTCT
Regimen should be given while prerparations are made to start with HAART as soon as
possible after delivery.
The appraoch to rediness preparation is the same as for non-pregnant adults. However,
pregnant women who are eligible and are willing to take HAART should not be on a
waiting list.
15.4 RECOMMENDED HAART REGIMENS
a) Initiation regimen – Regimen 1b
(CD4 ≤ 250 mm3, ALT < 100 U/L, creatinine normal and Hepatitis B sAg negative)

Monitor the patient closely during the first few months, including with ALT
tests at weeks 2, 4 and 8. Then monitor the patient according to pregnancy
requirements.
b) Pregnant women for special consideration
 ALT elevated, and/or
 Hepatitis B surface Ag positive
Commence on a mixed regimen, and avoid NVP
Stavudine (d4T) 30mg 12 hourly
AND
Lamivudine (3TC) 300mg daily OR 150 mg 12 hourly
AND
Lopinavir/ritonavir 400/100 every 12 hours
29



Request fasting cholesterol, triglycerides and glucose tests
Monitor 4 weekly unless pregnancy or medical condition requires more frequent
monitoring, or patient experiences side effects.
Tenofovir should be considered post delivery if not breastfeeding.
c) Women who become pregnant whilst on HAART
 These women should continue HAART throughout the pregnancy.
 Women who become pregnant on an efavirenz-containing regimen should have
efavirenz substituted with Nevirapine , monitoring ALT closely
 Test VL at least once during pregnancy; at least after two months of HAART. If
the VL is greater than 1 000 copies/ ml intensive adherence counselling should
be given with a repeat VL 1 month later. If there is no reduction in VL, the
HAART regimen should be changed to an appropriate regimen 2.
(Note:It is not necessary to introduce nevirapine graduallly if previously on efivarenz)
d) Regimen 2 in pregnancy - Regimen 2a
15.5

CLINICAL AND LABORATORY MONITORING DURING
ANTENATAL CARE
Monitor pregnant women on HAART at least once every 4 weeksand according
to:
o The antiretroviral drugs used
o The underlying medical condition
o Obstetric considerations.
o At each follow-up visit:
o Determine patient adherence to HAART
o Determine whether patient is experiencing any adverse reactions to
HAART
o Monitor pregnant women initiated on Regimen 1b more closely
 Request ALT at weeks 2, 4, 8 and 12 then 6 monthly if normal
 Couple ALT elevation with a symptom directed evaluation.
15.5.1 MANAGEMENT OF ELEVATED ALT IN PREGNANCY
 Stop HAART if:
o Grade 3 or more ALT elevation occurs (>5 times upper limit of
normal)
 AND/OR
o Patient develops symptoms of hepatitis
 AND/OR
o Patient develops grade 3 or 4 rash,
 Continue with co-trimoxazole prophylaxis.
 Restart with lopinavir/ritonavir based HAART once the patient’s symptoms
and enzymes have returned to at least 2 times upper limit of normal.
30
15.6
HAART DURING CHILD BIRTH





Offer HIV testing to women who did not take up tha test during pregnancy.
This should be done during first stage of labour or shortly after childbirth.
An elective Caesarean section done for obstetric indications before 38 weeks
should offer additional benefit for PMTCT.
Continue HAART during labour an dater delivery.
Ensure that pregnant women on the PMTCT regimen do not miss doses
around the time of delivery.
Keep an emergency stock of HAART in the Labour ward for women who
present to the labour ward after hours and do not have their medication with
them.
15.7 TREATMENT STRATEGY FOR INFANTS BORN TO HIV POSITIVE
WOMEN
 Administer sdNVP as soon after birth as possible but within 72hours period
 Commence AZT soon after birth
o For 7 days
o For 28 days to infants born to women who received suboptimal
PMTCT or HAART
 where no maternal ARVs were taken
 where maternal ARVs (PMTCT or HAART regimen) were taken
for less than 4 weeks
 where women only received sdNVP
Table 9: PMTCT Infant Dosing Guide
Drug
Weight
Dose
NVP syrup
>2kg
0.6ml
(10mg/ml)
(6mg) stat
< 2kg
0.2ml/kg stat
(2mg/kg)
AZT syrup
>2kg
1.2ml 12 hrly
(10mg/ml)
(12mg 12 hrly)
Notes
To be administered as soon after birth
as possible as a single dose(sdNVP)
For 1 week if mother received 28 days of AZT or
HAART, otherwise for 4 weeks. Administered with
a 2ml syringe
15.8 POSTPARTUM CARE



Offer HIV testing to women who were not tested during pregnancy or around
time of childbirth.
Provide infant feeding counselling, assessment for indications for HAART
and other HIV-related care to HIV positive women.
Provide women who plan on leaving the geographic area of the clinic
following delivery with:
o A referral letter containing all relevant clinical details
o Details of clinic that offers PCR testing
31
o Sufficient antiretroviral medication to ensure that she will not run out
of medication before reaching the referral clinic.
 Discuss family planning choices.
 Request women to return at six weeks post delivery for:
o Cervical cancer screening,
o For infant diagnosis (if not performed by the baby wellness clinic)
o To ensure the infant has been initiated on co-trimoxazole prophylaxis.
 Request women to return for cervical smear results, infant HIV diagnosis and
appropriate referral for ongoing care.
 Refer women who have completed postnatal care to a Comprehensive Plan
service point.
15.9
SPECIAL SITUATIONS FOR PREGNANT WOMEN REQUIRING
HAART
15.9.1 CONCOMITANT TUBERCULOSIS

Screen pregnant HIV positive women for signs and symptoms of tuberculosis.
o Collect sputum for microscopy and TB culture, and
o Do a safe chest radiograph
If TB is diagnosed (clinically as above or microbiologically) there are two scenarios to
consider:
a) The pregnant women who develop tuberculosis while on HAART
Regimen 1a: If beyond her first trimester should continue on this regimen.
Regimen 1b: Continue on this regimen and monitor ALT every two weeks.
Regimen 2: Change to regimen 2c until two weeks after completion of antiTB treatment
b) The pregnant women who qualify for HAART and are diagnosed with TB
before commencing HAART
 Prioritise treatment of TB
 Start HAART only after patient has stabilized on TB treatment (at least two
weeks later).
 Delay starting HAART in the first trimester, unless there is severe morbidity or a
very low CD4 count < 50 cells/ mm3.
 Use Nevirapine only with tight toxicity monitoring
 Consider replacing Efivarenz with Lopinavir/2Xritonavir
32
SECTION 2: MANAGEMENT OF HIV & AIDS
INFECTION IN CHILDREN
Guidelines for the management of HIV and AIDS in Children are available on print and
have been posted on the DOH website. This section seeks to addresss the HAART
aspects in children.
1. INDICATIONS FOR HAART IN CHILDREN
1.1 Clinical Criteria
o Confirmation of diagnosis of HIV infection
o Recurrent (> 2 admissions per year) hospitalizations for HIV complications or
prolonged hospitalization for HIV (> 4 weeks) OR
Table 10: Clinical criteria
Child less than 1 year
1 – 5 years
>5 years
Symptomatic
( WHO stage II, III, IV) or CD4
 35% or absolute count below
1500
Symptomatic (stage III, IV) or
CD4  20%
Symptomatic (stage III, IV) or
CD4 <15% or CD4 <250 cells.
1.2 Social criteria
 These criteria are about ensuring adherence to treatment:
o At least one identifiable caregiver who is able to supervise the child for
administering medication (all efforts should be made to ensure that the
social circumstances of vulnerable children, e.g. orphans, are addressed
so that they too can receive treatment)
o Disclosure to another adult living in the same house is encouraged so that
there is someone else who can assist with the administration of
medication
2. TREATMENT OF MOTHERS/ CAREGIVERS/OTHER FAMILY
MEMBERS
 Always ask about the caregiver’s health, and the health of other members of the
family
 Ensure that mothers and other family members access medical care timeously,
including HAART if needed
 Attend mothers or caregivers at the same time as their children where possible
HIV positive mothers in order to decrease the number of clinic visits and
associated costs and time away from work.
33
3. RECOMMENDED PAEDIATRIC HAART REGIMENS






Start all infants less than 6 months of age who require antiretroviral therapy on
treatment under supervision by a doctor trained in HAART.
Stavudine solution requires refrigeration. If no ‘fridge’ is available, stavudine
capsules may be opened and dissolved, and the required amount administered to
the child. The rest can be discarded.
Substitute stavudine capsules with Zidovudine suspension may if the caregiver
experiences difficulty
Recommend lopinavir/ritonivir for:
o Children under 3 years as one can assume that most in this age group will
have received nevirapine for PMTCT. Resistance mutations have been shown
to occur in almost half of children exposed to nevirapine in this fashion. Most
resistance mutations fade within the first year. It is still unknown whether
children with resistance mutation will have achieved resistance and therefore
inadequate response to therapy with a regimen including an NNRTI.
o Children under 3 years have higher viral loads and often have adherence
problems and this makes lopinavir/ritinovir preferable.
Switch to tablets or capsules from syrups or solutions as soon as possible.
Keep lopinavir/ritonavir at (< 25º C) Refrigerate till dispensing.(can be kept out
of the fridge for 42 days).
Table 11: Recommended Paediatric HAART Regimens
0 months up to 3 years
Over 3years and >10
kg
1st Line
2nd Line
Stavudine
Stavudine
Lamivudine (3TC)
Lamivudine (3TC)
Lopinivir/ritonavir
Efavirenz
Zidovudine (AZT)
Zidovudine (AZT)
Didanosine (ddI)
Didanosine (ddI)
Nevirapine/ Efavirenz*
Lopinivir/ritonavir
* Efavirenz if the child is over 3 years and nevirapine if <3years
34
4. SINGLE DRUG SUBSTITUTION OF STAVUDINE WITH ABACAVIR
Children who develop resistance or toxicity to Stavudine should be switched to
Abacavir.
4.1 Toxicity warranting a switch:
o Lactic acidosis
o Peripheral neuropathy
o Lipodystrophy.
o Other
manifestations
like
insulin
resistance,
hyperglycemia,
hypertriglyceridaemia, hypercholesterlaemia and low HDL levels.
o Viral load >400 copies/ml – continue
o Viral load > 1000 copies/ml switch to 2nd line
35
SECTION 3: ADHERENCE TO HAART
1. GENERAL CONSIDERATION

The Adequate Preparation of patients; support of patients during treatment
initiation and ongoing adherence monitoring and support are all critical to
ensuring maximum sustained adherence

Adherence to HAART is essential to maintain long-term health benefits and
avoid development of drug resistance.

It is not possible for health care providers to reliably predict which individuals
will ultimately be adherent to their treatment plan. This is because adherence
does not correlate with gender, cultural background, socio-economic or
education level nor does it correlate with language barriers between provider and
patient.

It is therefore essential to provide all patients with a comprehensive strategy to
support adherence that includes education, training, counselling, appropriate
tools and community support.

The plan must make use of all members of the health care team, as well as the
patient’s family and the community the patient comes from.
2. ADHERENCE SUPPORT, ASSESSMENT AND MONITORING
2.1 Role of the health care team









There is evidence that adherence to treatment and positive lifestyle choices
decreases as time progresses.
Thus, monitoring and ongoing support of adherence is essential both at the
clinic level as well as in the community.
New diagnoses, unexplained symptoms, opportunistic infections and high pill
regimens are barriers to adherence.
Patients might have to be reassured and treated symptomatically if they
experience minor symptoms like nausea and vomiting, on treatment initiation
advise them on the transient nature of these.
Patients with depression might require referral and long-term management as
depression impacts negatively on adherence.
A supportive and trusting relationship between the patient and members of
the health care team is essential.
Optimal adherence requires full participation of the multi-disciplinary health
care team: the patient, their family members and the community.
Every patient interaction with staff at the clinic is an opportunity for
reinforcement of positive behaviour change.
Supportive and non-judgmental attitudes and behaviours will encourage
patient honesty regarding adherence and problems.
36
2.2 The clinic team should commit to the following:





Communication between clinic visits, referral points as appropriate.
Ongoing adherence support with evaluation, monitoring and appropriate
interventions
Timely response in the form of ongoing counselling and reassurance to any
barriers such as adverse events, interim illness, issues around stigma and
disclosure.
Interim management during holidays or other absences must be discussed
with the patient.
If there is sub-optimal adherence, there should be extra support e.g.:
o Investigate these barriers and assist with overcoming these
o Recommend more visits with more frequent adherence checks
o Enlist support of family/friends/ partners/ support group members
o Review teaching approach
o Increase home visits
o Use reminders and reinforce with adherence tools
3. DEFINITION OF ADHERENCE TO HAART



Success of HAART hinges on the correct medication-taking behavior.
Ideal adherence means a patient must take more than 95% of their doses (i.e.
missing less than 3 doses in a month)
If a patient is taking less than 95% of their doses, they are at risk for developing
viral resistance and ultimately virological failure.
Patients taking <80% of their doses are unlikely to have any durable virological
suppression. They should be targeted urgently for adherence improvement and 3month follow-up as discussed in strategies to promote adherence below.
4. ISSUES WHICH IMPACT ON ADHERENCE
4.1
Personal:
o Internalized stigma; external discrimination
o Unresolved grief reaction
o Lack of Disclosure
4.2
Environmental:
o Pill burden and side effects
o Income and food insecurity – underlying starvation
o Negative staff attitudes
o Lack of training of staff
o Shift work
37
5. STRATEGIES TO PROMOTE ADHERENCE
 The whole clinic team needs to support adherence at all points of intervention.

Adherence counsellors (where possible, patient advocates; community health
care workers, treatment supports) need to:o Spend time with the patient and explain the goals of therapy and need for
adherence to ensure virological suppression as many times as is
necessary.
o Consider monitoring of medications such as co-trimoxazole prior to
HAART initiation.
o Negotiate a treatment plan that the patient can understand and to which
he/she commits.
o Tailor pill taking time to suite the patient’s lifestyle.
o Encourage disclosure to family or friends who can support the treatment
plan.
o Inform the patient of potential side-effects – severity, duration and
strategies for management of these.
o Establish ‘readiness’ to take medications before HAART initiation.
o Provide adherence tools where available: written calendar of medications,
tick sheets, patient diaries and patient self care ‘contracts’ etc.
o Encourage use of pill boxes, alarms, pagers or other available mechanical
aids for adherence.
o Explain to patients how to avoid adverse drug-drug interactions. The
patient must disclose any over-the-counter drugs and traditional
medicines. Other medications as well as some traditional medicines
cannot be taken concurrently with HAART because they may result in
poor HAART therapeutic levels in the blood leading to viral resistance.
Herbs and other over the counter preparation can lead to renal and liver
toxicity, complicating the clinical picture of adverse events.





Anticipate, monitor and treat side-effects.
Include adherence discussions in support groups.
Develop links with community-based organizations to support adherence.
Encourage links with support groups.
Create links with patient advocates.
6. PRE-TREATMENT ADHERENCE PACKAGE





Provide pre-treatment information and education as per visit schedule is critical
for all patients.
Specific strategies are needed for young patients.
Introduce patient to the therapeutic counsellor and patient advocate if available
and if agreed to or treatment buddies nominated by patient.
Arrange home visit if available to be undertaken by the nominated community
care giver, or trained home based carer or other volunteer health care worker.
Use assessment questionnaire to investigate potential adherence barriers and
investigate strategies to overcome these like;
o Access to drug and alcohol counseling
o Social welfare for grant access.
38
o Emergency relief for nutritional support.
o Support with disclosure.



Take Co-trimoxazole count one month prior to commencing therapy. This is not
to be used to exclude people from HAART. It is meant to reinforce daily
medication-taking behaviour from the beginning. It is also meant to identify
potential problems before starting HAART.
Encourage attendance and participating in a support group. These should be
ideally run by community members but might need to be supported by the clinic
staff or adherence/ therapeutic counselors or social workers.
Consider reward mechanisms for >95% adherent patients e.g. less waiting (faster
queues)
7. ADHERENCE MEASURING TOOLS: (SEE ADULT PATIENT
ADHERENCE RECORD & MONITORING FORM - PARMF)





Pick up dates with variance to actual appointment dates need to be recorded, and
followed up with the patient immediately if there is a significant variance
Return of pills used to calculate pill usage
Use 7 or 30 day recall of missed pills to assess non-adherence
Visual analogue scales can also be used to measure the patient’s assessment of
their own adherence according to a scale used by the treatment site.
Set questions on adherence can also be asked at times of pill pick up to further
monitor adherence
8. ADHERENCE PACKAGE FOR PATIENTS ON TREATMENT
At each visit the following needs to be done:
 Count HAART pill-returns count (% doses missed) .Adherence goal is >95%
doses taken. Patients with adherence <80% require increased adherence support
(see below).
 Do tablet count before the patient sees the doctor (can be done by the PA,
Pharmacist Assistant, Nursing Assistant or Community Care worker).
 Doctor should review the count to evaluate adherence.
 Missed/late clinic visits should trigger concerns about adherence.
 Include <95% adherence patients in list for discussion and follow-up.
 Intervene when a historical review of pill pick up dates against actual dates since
last viral load testing highlights nonadherence trends Routine adherencediscussion (education) with the adherence counsellor is of value.
 Avail yourself for questions and counseling patients when nonadherence occurs
 Get a better profile of the patient and their environment through feedback from
the therapeutic and adherence counselors.
 Encourage participation in a support group where there is indication of failing
adherence.
 Continue monthly visit with therapeutic counsellors for first three months and
quarterly thereafter.
 Arrange regular community visits by patient advocates or community adherence
workers for follow-up of patients who have shown non-adherent behaviour.
39
9. STEP-UP ADHERENCE PACKAGE FOR PEOPLE WITH REDUCED
ADHERENCE OR VIROLOGICAL FAILURE











This is necessary when the adherence assessment is <80% at any visit, with or
without viral or clinical failure to:
o Establish the cause and suggest appropriate interventions.
o Re-educate the patient (and their buddy) about the importance of
adherence.
o To re-emphasize long-term benefits
o To assign a community adherence worker or patient advocate to patient if
not attached.
Evaluate the support structures in place.
o Are they appropriate?
o How can they be improved?
o What alternatives are there?
Reinforce the use of adherence tools e.g. pillboxes and/or daily dosing diary.
Insist on participation in a support group or link with a patient advocate/
community adherence worker.
Consider doing a psychological profile and respond appropriately.
Check the family situation (social worker and therapeutic counsellor).
Redo the Cage Assessment for alcohol abuse and other abused drugs.
CAGE = Cutback; Anger; Guilt, Eye Opener.
Increase home visits by therapeutic counsellors/patient advocates to daily or
weekly, at a minimum (spot pill counts to be done at home).
Consider directly observed therapy for an agreed period.
Promote self-efficacy training.
40
SECTION 4: DIAGNOSIS AND MANAGEMENT OF
ADVERSE EVENTS
1. PRINCIPLES OF MANAGING ADVERSE EVENTS






Establish whether the adverse event is due to antiretroviral agents, other
medication or other illness.
Never stop only one antiretroviral drug. If there is a need to discontinue HAART,
all antiretroviral medications must be stopped together.
Individual drugs may be switched due to intolerance as shown on Table 2 . A
single drug switch should not be made if the patient is known to be virologically
failing.
Clinicians may continue HAART if there is a mild or moderate adverse reaction.
Adequate symptomatic therapy, counselling to reassure patients and monitoring
are essential if this is done.
Potentially life-threatening side effects of HAART are: lactic acidosis, severe
drug-induced hepatitis, kidney toxicity, pancreatitis, severe drug rash and
abacavir hypersensitivity reactions. All therapy should be interrupted
immediately in these situations.
Adverse events should be recorded and reported regularly to the HIV&AIDS
programme at Head Office. Serious adverse events (SAEs) and deaths should be
reported within 48-72 hours to the MCC National Adverse Drug Event
Monitoring Centre, phone (012) 312-0000 Pretoria; or (021) 447-1618, fax: (021)
448-6181 Cape Town.
Adverse event forms should be available at all centres.
2. IMPORTANT ADVERSE REACTIONS
Table 12: Important HAART adverse reactions and safety monitoring
Antiretroviral
Adverse Reactions
Recommended safety
monitoring
Abacavir (ABC)
A potentially fatal hypersensitivity reaction Clinical
develops in approximately 3% -5% of patients.
Symptoms usually appear within 6 weeks of
treatment initiation. Suspect reaction if symptoms
from 2 or more of the following groups are present:
 Fever
 maculopapular pruritic generalised rash
 gastro-intestinal symptoms
 other symptoms (including pharyngitis,
dyspnoea, cough, musculoskeletal
disorders, malaise, fatigue,
lymphadenopathy and paraesthesia)
Never give abacavir to a patient who
has previously developed an abacavirhypersensitivity reaction
41
Didanosine (ddI)
Efavirenz (EFV)
Lamivudine (3TC)
Lopinavir/
Ritonavir
Nevirapine (NVP)
Ritonavir
Stavudine (d4T)
Tenofovir (TDF)
Zidovudine (AZT)
Pancreatitis, peripheral neuropathy, GIT effects Clinical
(bloating,
flatulence,
nausea,
diarrhoea),
hyperlactataemia, lactic acidosis.
CNS disturbances (dysphoria, vivid dreams, Clinical
distractedness, dizziness)
Skin rash, hepatitis
Congenital anomalies – avoid during 1st trimester of
pregnancy.
Generally well tolerated.
Clinical
GIT symptoms (mainly diarrhoea), lipid and glucose Fasting
cholesterol
and
abnormalities, lipodystrophic changes.
triglycerides and glucose at
baseline, 6 months and
thereafter every 12 months.
Skin rash (16%), nausea, vomiting,
ALT at baseline and at week 2,
hepatitis (can be fatal).
4, and 8, and 12 and any time
hepatitis symptoms occur
Bad taste, GIT symptoms, especially diarrhoea.
Fasting
cholesterol
and
Raised liver enzymes, raised cholesterol and triglycerides and glucose at
triglycerides and glucose intolerance, lipodystrophic baseline, 6 months, and
changes.
thereafter every 12 months.
Peripheral
neuropathy,
hepatic
steatosis, Clinical
hyperlactataemia, lactic acidosis, pancreatitis.
Nephrotoxicity, bone demineralisation
Check creatinine at baseline
and 6-monthly
Bone marrow suppression (anaemia, neutropenia), Hb and neutrophils count at
GIT
symptoms,
myopathy,
headaches, baseline, then at months 1, 2, 3
hyperlactataemia, and lactic acidosis.
and 6.
3. SPECIFIC ADVERSE REACTIONS
3.1 Symptomatic hyperlactataemia and lactic acidosis

Lactate is normally produced by all the body’s cells as part of anaerobic
metabolism. Nucleoside reverse transcriptase inhibitors (NRTIs) have the
potential to directly inhibit the human enzyme mitochondrial DNA polymerase
gamma, which is responsible for mitochondrial DNA synthesis. Reduced DNA
synthesis results in less synthesis of essential mitochondrial proteins. The
consequence is the formation of mitochondria which are structurally and
functionally impaired, resulting in decreased oxidative capacity of each
mitochondrion. Anaerobic metabolism with lactate overproduction and cellular
dysfunction is the result.

Different NRTIs have different risk profiles for causing hyperlactataemia. These
drugs have only been implicated if used in combination with higher risk drugs or
in patients with co-morbidities. Their risk is directly proportional to their
inhibitory effect on polymerase chain reaction in the following order (highest to
lowest risk):
o Combination of didanosine (ddI) and stavudine (d4T)
o ddI
o d4T
o Zidovudine (AZT)
o Lamivudine (3TC)
o Abacavir (ABC)
42
o Tenofovir (TDF).

Other manifestations of NRTI mitochondrial toxicity are:
o Hepatic steatosis
o peripheral neuropathy
o lipoatrophy
o Pancreatitis
o Myopathy
o Cardiomyopathy
o HIV-associated neuromuscular weakness syndrome (a Guillain-Barre like
syndrome that occurs secondary to NRTIs) and
o cytopaenias.
3.1.1 Hyperlactataemia and lactic acidosis


A normal venous lactate is less than 2, 5 mmol/l and arterial lactate less than 2, 0
mmol/l.
Hyperlactataemia is present when:
o Lactate is raised, but
o Blood pH is > 7.35 and
o Standard bicarbonate > 20,


It may be asymptomatic or symptomatic.
Asymptomatic hyperlactataemia is common when using NRTIs (occurs in up to
25% of patients on NRTIs), but does not predict for the symptomatic form of the
disease. Routine monitoring of lactate is not recommended if the patient is
asymptomatic.

Lactic acidosis is diagnosed when:
o Standard bicarbonate <20 together with
o Raised lactate.
o Lactate > 5.

To reach this stage, significant failure of the physiological compensating
mechanisms is present, and this carries a much worse prognosis.
In lactic acidosis the pH may be in the normal range (due to respiratory
compensation) but the standard bicarbonate is always <20.


Symptomatic hyperlactataemia occurs in 0.4 - 9% of patients on NRTI therapy
whereas lactic acidosis occurs in 0.1-0.4%.
3.1.2 Risk factors
The following have been identified as risk factors:




High body mass index (>28) and rapid weight gain.
Female gender.
Pregnancy.
Underlying liver disease.
43

Age – symptomatic hyperlactataemia/lactic acidosis appears to be unusual in
younger children.
3.1.3 Diagnosis
Apply the rule: if you consider the diagnosis, do the laboratory investigations
immediately. Delays in diagnosis may be life-threatening.

Many other conditions may result in raised lactic acid. Examples are:
o Sepsis
o Severe anaemia
o Hepatic failure
o Renal failure
o Pancreatitis,
o severe cardiac failure
o Severe dehydration
o Thiamine deficiency
o Treatments like metformin for diabetes mellitus.

Hyperlactaemia/lactic acidosis secondary to NRTIs is thus a diagnosis that
should be made only once these other possible explanations for raised lactate
have been excluded.

Symptoms may be very non-specific and vague, and generally have been present
and getting worse for weeks or months. Key symptoms and signs include:
o Unintentional loss of weight (especially > 5%)
o Gastro-intestinal symptoms, including nausea, vomiting, loss of appetite,
abdominal pain.
o Weakness and fatigue
o Dyspnoea, tachypnoea without respiratory cause
o Unexplained tachycardia
o Myalgia
o Peripheral oedema
o Peripheral neuropathy
o Lipoatrophy

Symptomatic hyperlactataemia/lactic acidosis usually occurs after:
o Patients have been on NRTIs for several months (median 10 months).
o Initially experiencing resolution of HIV and opportunistic infection
related symptoms,
o Patient has gained weight in the months after starting HAART
o Patient is virologically suppressed then experiences deterioration
o Onset of hyperlactataemia and its associated weight loss and symptoms.

It is unusual for symptomatic hyperlactataemia/lactic acidosis to develop after 2
years on therapy.
44

Clinical assessment should include:
o Evaluation of the respiratory rate
o Abdominal examination (for associated fatty liver and pancreatitis)
o Assessment for peripheral neuropathy.
o Evaluation for metabolic acidosis (tachypnoea in the absence of a
respiratory cause is suggestive of metabolic acidosis).

Make the diagnosis by measuring venous or arterial lactate. The venous blood
sample should be taken without the use of a tourniquet in a sodium fluoride tube.

Use point-of-care devices for lactate measurement where access to a laboratory
that is able measure lactate is difficult.

Check lipase, liver functions and glucose in all patients with confirmed
symptomatic hyperlactataemia/lactic acidosis to assess for co-existent
pancreatitis, steatohepatitis and diabetes.
A blood gas should also be checked in all patients with symptomatic
hyperlactataemia to confirm or exclude metabolic acidosis.

3.1.3.1 Differential diagnosis

Other causes for LOW to consider are:
o Opportunistic infections (ask about TB symptoms)
o Chronic diarrhoea with malabsorption
o Virological failure
o Depression
o Malignancy
o Undiagnosed diabetes
o Poor diet
3.1.4 Confounders

HIV positive patients frequently present with infective gastroenteritis
with diarrhoea and vomiting. If severe this may result in profound
dehydration with poor tissue perfusion and a raised lactate. In this
situation once the patient is resuscitated with fluids the lactate will
normalise. If the lactic acidosis is incorrectly attributed to the NRTIs
in this situation an inappropriate interruption and switch in therapy
may result. This may compromise future HAART options.

Similarly, septicaemic illnesses may result in lactic acidosis that will
resolve with fluid resuscitation, appropriate antibiotics and other
supportive therapies and it may not be necessary to stop or change
ART in this situation.
3.1.5 Prevention

Start women with a body mass index (BMI) > 28 (high risk group) on AZT
rather than D4T or switch them to AZT if they gain weight to a BMI > 28 on
45





HAART. If such women have an Hb < 6.5g/dl the switch from D4T to AZT
should be deferred until Hb has normalized.
Recognize the syndrome before the person becomes acidotic as the most
effective prevention by :
o Educating patients to report any loss of weight, abdominal pain or
vomiting lasting more than a few days, excessive fatigue, lipoatrophy
or peripheral neuropathy symptoms.
o Monitoring weight should be monitored at every clinic visit and when
they drop by > 5% a lactate should be done, even if no other
symptoms are present
o Measuring lactate of any patient with a severe or rapidly progressive
NRTI-induced neuropathy (typically due to D4T or ddI)
Avoid using ddI and D4T in the same HAART regimen as this combination
carries the highest risk for mitochondrial toxicity.
Symptoms tend to occur long before severe laboratory abnormalities are
present.
The mortality and morbidity of the condition dramatically increases in the
presence of acidosis.
The mortality rate with severe lactic acidosis is 30-60%.
3.1.6 Management

Once the diagnosis is confirmed (raised lactate and EXCLUSION of other
causes), the following guidelines are suggested:
o Stop the regimen even before the diagnosis is biochemically
confirmed if you have a high index of suspicion.
o Do not stop the NRTIs alone, stop the entire regimen. It is better to
interrupt a regimen for a short period than to continue a toxic regimen
in the presence of suspected lactic acidosis.
3.1.6.1 In patients with mild hyperlactataemia and minimal symptoms (lactate
2.5-5 and no metabolic acidosis – standard bicarbonate > 20)
o
o
o
o
The D4T should be switched to AZT and
The lactate rechecked within 3 days and then weekly until normalized.
Stop HAART If the lactate cannot be monitored in the way described
Stop HAART and follow the guidelines below if symptoms are severe or
the lactate continues to rise or symptoms get worse despite the switch.
3.1.6.2 Patients with moderately severe hyperlactataemia/moderate metabolic
acidosis (lactate 5-10 and/or standard bicarbonate 15-20)
o Stop HAART and observe as inpatient for 1-2 days and
o Give oral vitamins (vitamin BCo 2 tablets bd and thiamine 100mg
bd) ,
o Hydrate well (orally or IVI)
o Exclude sepsis
o Exclude OIs.
46
o Recheck lactate and discharge for outpatient follow-up if clinically
stable.
o Recommence HAART Regimen 1d (Tenofovir, 3TC, EFV) only
when lactate and bicarbonate has normalized (this may take months).
3.1.6.3 Patients with severe hyperlactataemia (lactate > 10 without metabolic
acidosis) or significant lactic acidosis (raised lactate regardless of level and
significant metabolic acidosis – standard bicarbonate < 15)



The mortality is high in this scenario (up to 60%). These patients should
preferably be managed in a high care facility as such:
o Stop HAART
o IVI Thiamine 100mg 12hrly and BCo 1 amp 12hrly
o IVI fluids
o Blood culture/ urine culture/ septic search AND
o Broad-spectrum antibiotic (e.g. third-generation cephalosporin or coamoxyclav). This is important because sepsis may mimic or precipitate
NRTI-associated lactic acidosis.
o IVI NaHCO3 if profound acidosis
o Ventilation if respiratory fatigue occurs
o Dialysis,
o Inotropes and
o Other supportive measures as necessary
Monitor:
o Lactate
o Blood gas
o Lipase
o ALT and
o Alkaline Phosphatase.
Recommenced on HAART Regimen 1d (Tenofovir, 3TC, EFV) kaletra when
lactate has significantly decreased and they are clinically improved (this may
take weeks to months).
NOTE: Neither d4T nor ddI should be used ever again in any patient who has had
symptomatic hyperlactataemia/lactic acidosis.
3.2 Nausea and vomiting
 Actively manage nausea due to antiretroviral medication, or adherence will
suffer. The common causative agents are AZT and ddI.
 Administering anti-emetics half an hour before the antiretroviral dose up to 3
times daily may be helpful. If the nausea does not settle, refer to a doctor
trained on HAART.
 Check for jaundice and take blood for ALT as nausea and vomiting may be
the first symptoms of drug-induced hepatitis
47
3.3 Drug Rashes
















Drug rashes are typically associated with Nevirapine (and the Abacavir
hypersensitivity syndrome which is covered above). Less commonly they are
associated with Efavirenz and rarely with other antiretrovirals. A number of
other drugs used in patients with HIV (e.g. Co-trimoxazole and TB
medications) may also result in drug rashes.
About 15% of patients started on Nevirapine will develop a drug rash. This
typically occurs in the first 3 months. It typically presents with a morbiliform
or maculo-papular eruption but may progress to blistering, desquamation and
a Stevens-Johnson syndrome.
Most Nevirapine skin rashes are mild and will settle despite continuing the
drug. However, about 1/3 of patients require that Nevirapine is stopped.
Check the following in patients presenting with a Nevirapine skin rash:
o ALT
o Temperature
o Asked about systemic symptoms.
Stop Nevirapine (together with the rest of the HAART regimen)
immediately:
o Any mucosal involvement (conjunctival, oral and/or genital)
o Any angio-oedema
o Fever or systemic symptoms such as myalgia
o Blistering, desquamation or ulceration
o Associated hepatitis (rise in ALT)
o Associated arthritis
Continue Nevirapine if patients have a mild rash with none of the above
features (but the 2 week dose escalation from 200mg daily to 200mg b.d.
should not be made until the rash has settled).
Use topical steroids and oral antihistamine for milder cases and the patients
should
Review in 2-3 days.
Warn patients to come earlier if any of the above severe manifestations
occur.
Avoid systemic steroids.
Re-initiate HAART with Efavirenz in place of Nevirapine once the rash has
resolved.
Consult a doctor trained in HAART when re-initiating HAART in patients
who have had a life threatening Stevens Johnson syndrome on Nevirapine.
The management of Efavirenz rash follows the same principles
Consult a doctor trained in HAART when re-initiating HAART in patients if
HAART was stopped due to EFV rash
Exclude rash caused by IRIS as not all rashes presenting on HAART are drug
rashes.
A number of skin rashes may worsen or first manifest during immune
recovery (eg. acne, molluscum contagiosum, warts, folliculitis).
48
3.4 Abdominal pain
 Abdominal pain in a patient on HAART can be caused by a number of
serious problems, and should never be ignored.
Important causes to consider are:
o Symptomatic hyperlactataemia and lactic acidosis (check lactate
o Pancreatitis (check lipase)
o Hepatitis / steatohepatitis (check liver functions and assess for
hepatomegaly)
o Opportunistic infections or IRIS (e.g. abdominal TB)
o Gastrointestinal intolerance of medication
o Unrelated causes (e.g. pregnancy, diabetic ketoacidosis, appendicitis,
peptic ulcer disease, pelvic inflammatory disease, urinary tract
infections)
3.5 Peripheral neuropathy

Peripheral neuropathy may herald the development of symptomatic
hyperlactataemia in patients on d4T

Peripheral neuropathy may result from:
o HIV infection
o INH or the
o d4T
o ddI
NOTE: If a new neuropathy develops or an existing neuropathy rapidly
worsens after d4T or ddI initiation then a d4T/ddI induced neuropathy is
likely
Symptoms of peripheral neuropathy are:
o Nocturnal pain in the toes and feet usually the first symptoms
o Paraesthesia (burning and tingling)
o Sensory loss and motor impairment (may occur later)

If peripheral neuropathy is due to mitochondrial toxicity resulting from ddI or
d4T initial treatment should involve:
o Symptomatic therapy with simple analgesia
o Amitriptyline
o Vitamin supplementation (B6 and BCo).

If the symptoms progress despite this and particularly if there is any sensory
loss or motor deficit the d4T should be switched to AZT.
Switch to AZT provided there is no neutropaenia or anaemia (Hb below 6.5 g
/ dl ) or neutropenia (Neutrophil count below 0.5 X 10 9 / l)
Use Tenofovir in patients who have severe neuropathy and anaemia or
neutropaenia .


49
3.6 Efavirenz neurological side effects



Efavirenz may cause CNS disturbances (dysphoria, vivid dreams,
distractedness, dizziness, depression etc.)
In the majority of patients this is self-limiting despite the drug being
continued
Switch to Nevirapine if these symptoms do not resolve after a few weeks and
are disabling (if a switch from Efavirenz to Nevirapine is made the lead-in
dose is not required and nevirapine should be started at a dose of 200mg bd).
3.7 Pancreatitis
Causes of Pancreatitis may be:
o ddI or
o d4T and has been described in association with
o 3TC in children
o Hypertriglyceridaemia due to Kaletra in patients on HAART Regimen
2.(usually the triglyceride level is above 15 mmol/l)




Patients present with typical clinical features of pancreatitis (upper
abdominal pain, vomiting, etc)
Confirm the diagnosis by measuring lipase (amylase is non-specific in
patients with HIV as HIV-related salivary disease may result in elevation).
Lipase should be > 4 x upper limit of normal for the diagnosis to be made.
Management
o Stopping HAART regimen
o Admission
o IVI fluids
o Keep patient nil per mouth until clinically improved.
3.8 AZT-related anaemia and neutropaenia
Table 13: Grading of anemia and neutropaenia in adults
ITEM
GRADE I
TOXICITY
Hemoglobin
8.0-9.4 g/dL
Absolute neutrophil 1 - 1.5 x 109/L
count




GRADE II
GRADE III
GRADE IV
TOXICITY
TOXICITY
TOXICITY
7.0-7.9 g/dL
6.5-6.9 g/dL
<6.5 g/dL
0.75 - 0.99x 0.5 - 0.749 x < 0.5 x 109/L
109/L
109/L
These side effects typically occur within the first 3 months of initiating AZT
Check Hb and neutrophil upon starting or switching to AZT then after 1, 2, 3
and 6 months.
Reduce the dose to 200mg 12 hourly if the patient develops grade I or II
anaemia or neutropaenia on zidovudine.
Replace AZT with Tenofovir if there is no improvement after dose
adjustment.
50



Repalce AZT with Tenofovir in patients who present with grade III or IV
anaemia or neutropenia.
Blood transfusion may be required for severe anemia
Neutropaenia may be complicated by neutropaenic sepsis
3.9 Hepatitis









Each class of antiretrovirals is associated with a unique pattern of drug injury
Nevirapine is the commonest cause of drug-induced hepatitis among the
antiretrovirals resulting in clinically significant hepatitis (ALT>200 with
symptoms) in 2% of patients.
The NNRTIs (Nevirapine > Efavirenz) cause an immune-mediated
hypersensitivity hepatitis that almost exclusively occurs within 3 months of
initiating the drug
Patients may present with:
o acute onset of nausea and vomiting
o malaise
o jaundice and/or
o Right upper quadrant pain.
o LFTs show predominantly a transaminitis (ALT and AST elevation).
o Immune-mediated hypersensitivity phenomena (e.g. drug rash, drug
fever and eosinophila) which occur simultaneously.
Women with CD4 count > 250 and men with CD4 count> 400 are greater
risk of developing Nevirapine hepatitis (and rash).
Check ALT at baseline then at 2, 4, 8 and 12 weeks for patients on
Nevirapine.
Protease inhibitors (Kaletra) may also result in drug-induced hepatitis usually
presenting with a predominant transaminitis.
Exclude causes other than the antiretrovirals in patients with hepatitis
diagnostic. These include:
o Alcohol abuse
o Chronic viral hepatitis (B and C).(HAART-induced immune
reconstitution may result in an acute flare of viral hepatitis in such
patients - a form of IRIS)
o Other drugs (eg. INH, Rifampicin, PZA, Co-trimoxazole,
Fluconazole, antibiotics and alternative remedies)
o HIV cholangiopathy
o TB involvement of the liver (granulomatous hepatitis) or porta
hepatis nodes resulting in bile duct obstruction
Check ALT and HepBsAg before initiating HAART in all patients
An approach to managing patients with hepatitis on HAART:
 Consider all possible causes
 Continue therapy and repeat in 1 week if ALT elevated to 50-200 and patient
is asymptomatic
 Stop HAART and other drugs that could be causing hepatitis (eg. TB
treatment) and monitor ALT if ALT elevated 50-200 with symptoms of
hepatitis (nausea and vomiting, jaundice, right upper quadrant pain) and in all
in whom ALT elevated > 200 even if no symptoms,.
51


Assess patients with severe ALT derangement for features of liver failure
(confusion, metabolic flap and raised INR). Admit these patients and manage
appropriately for liver failure.
Patients with drug-induced hepatitis have often been on a host of drugs that
could possibly cause the hepatitis. Re-introduction of medication should only
be done when ALT has normalized and jaundice has resolved. Drugs should
be rechallenged in the following order as a general rule, while monitoring
ALT closely:
o Rechallenge treatments of active OI’s (e.g. TB drug rechallenge
according to local guidelines)
o Re-introduce of safer HAART regimen (eg. substituting Nevirapine with
Efavirenz if Nevirapine was in the HAART regimen when hepatitis
occurred.
o Rechallenge with prophylactic medication (eg. Co-trimoxazole)
o Manage patients with fatty liver/steatohepatitis according to protocols
for the associated hyperlactaemia
3.10 Hyperlipidaemia








Kaletra or ritonavir may cause hypertriglyceridaemia and
hypercholesterolemia thus at initiation, at 6 months then annually check :
o Fasting triglycerides
o cholesterol
o glucose
The main risk associated with hypertriglyceridaemia is pancreatitis (usually
when level is >15 mmol/l)
Hypercholesterolemia may result in atherosclerotic vascular disease
particularly in patients with other risk factors such as smoking, hypertension
and diabetes.
Address:
o Dietary advice (low fat diet)refer to a dietician
o Vascular risk factors (stop smoking, weight loss, increase exercise and
treat hypertension and/or diabetes) in patients with elevated cholesterol
and/or triglycerides.
Treat patients with hypertiglyceridaemia where the triglyceride level is >10
mmol/l medical therapy with a fibrate (e.g. Bezafibrate 400mg daily after
food
Treat patients with hypercholsterolaemia after an assessment of overall
cardiovascular risk and the cholesterol level.
Treat patients with a fibrate if their Framingham risk for MI is calculated to
be 20% over 10 years.
Simvastatin and most other statins are contra-indicated for use with PIs
because of drug interactions. However, Pravastatin and low dose Atorvastatin
are safe.
52
3.11 Glucose intolerance and diabetes





Glucose intolerance and diabetes may complicate therapy with d4T or
Kaletra
Monitor fasting glucose in patients on Kaletra at baseline, 6 months then
annually.
Check glucose if symptoms of diabetes occur in patients on d4T
Manage the diabetes as per standard protocols
Consider switching d4T to Tenofovir if diabetes develops on d4T
3.12 Lipodystrophy




HIV-associated lipodystrophy includes fat loss and/or fat accumulation in
distinct regions of the body. This includes increased fat around abdomen,
buffalo hump and breast hypertrophy in women (lipohypertrophy), and fat
loss from limbs, buttocks and face (lipoatrophy).
Lipoatrophy is closely associated with NRTI use (especially d4T, and to a
lesser extent AZT). Lipohypertophy may occur with NRTI’s and/or PI’s.
Switch from d4T to Tenofovir if significant lipoatrophy occurs.
Encourage exercise to reduce fat accumulation for lipohypertrophy
3.13 Gynaecomastia
 Less than 5 % of men on HAART will develop gynaecomastia which may be
bilateral or unilateral.This is most strongly associated with Efavirenz and ddI
use
 In most cases it resolves spontaneously over 1-2 years
 Switch drugs if its effects are severe (e.g. psychological distress).
3.14 Tenofovir nephrotoxicity






A minority of patients on Tenofovir with underlying renal disease and those
also exposed to other nephrotoxic drugs experience deterioration in renal
function.
In most cases it is reversible on stopping Tenofovir.
Tenofovir has also rarely been associated with Fanconi’s syndrome, resulting
from tubular dysfunction and wasting of phosphate, amino acids and other
substances from the renal tubules. Patients present with non-specific
symptoms such as malaise.
Before starting a patient on Tenofovir check their renal function and
creatinine clearance calculated (see Cockgraft-Gault formula). If creatinine
clearance is < 50ml/min Tenofovir should not be used
Check creatinine levels monthly until 6 months after initiation of Tenofovir.
Never combine Tenofovir with didanosine because of increased side effects
and poorer virological outcomes
53
Table 14: Recommended substitutions for specific side-effects
Regimen
D4T/3TC/EFV
Toxicity


D4T/3TC/NVP




AZT / 3TC / EFV




Tenofovir / 3TC / Lopinavir /
Ritonavir





AZT/ ddI / lopinavir / ritonavir






Tenofovir / 3TC / lopinavir /
ritonavir




d4T-related neuropathy or
pancreatitis
Persistent EFV-related
CNS toxicity
d4T-related neuropathy or
pancreatitis
NVP-related severe
hepatotoxicity
NVP-related severe rash
(but not life-threatening)
NVP-related lifethreatening rash
Stevens-Johnson syndrome
Lactic acidosis
AZT related anaemia or
neutropenia
Persistent EFV-related
CNS toxicity
LPV/r related GIT
symptoms
LPV/r related
hypercholesterolaemia
Lipodystropy
Impaired glucose tolerance
Drug substitution


Switch d4T to Tenofovir
Switch EFV to NVP

Switch d4T to Tenofovir





Switch NVP to EFV
(except first trimester
pregnancy)
Switch NVP to EFV
Switch NVP to Tenofovir
Switch NVP to Tenofovir
Switch d4T to Tenofovir


Switch AZT to Tenofovir
Switch EFV to NVP

Consult doctor trained in
HAART
Antidiarrhoeals and other
symptomatic therapy
Diet +/- fibrate
Advise exercise
Antidiabetic agents
(warning: metformin may
increase risk of lactic
acidosis).
Switch AZT to d4T
(monitor closely for
peripheral neuropathy and
lactic acidosis)
Consult doctor trained in
HAART
Antidiarrhoeals and other
symptomatic therapy
Diet +/- fibrate
Advise exercise
Antidiabetic agents
(warning: metformin may
increase risk of lactic
acidosis).
Consult doctor trained in
HAART
Antidiarrhoeals and other
symptomatic therapy
Diet +/- fibrate
Advise exercise
Antidiabetic agents
(warning: metformin may
increase risk of lactic
acidosis).




AZT related anaemia or
neutropenia
ddI related pancreatitis
LPV/r related GIT
symptoms
LPV/r related
hypercholesterolaemia
Lipodystropy
Impaired glucose tolerance

LPV/r related GIT
symptoms
LPV/r related
hypercholesterolaemia
Lipodystropy
Impaired glucose tolerance










54
4. DRUG INTERACTIONS



Drugs belonging to the NNRTI and PI classes have a number of important drug
interactions that need to be considered.
These result from the fact that they are substrates of the cytochrome P450
enzyme system in the liver and intestine.
PIs are generally inhibitors of these enzymes; Nevirapine an inducer and
Efavirenz may be an inducer or inhibitor. Exceptions do, however, occur. Drugs
that are commonly involved in these interactions are:
4.1 Inducers
Carbamazepine, Phenytoin, Phenobarbitone
Rifampicin
4.2
Inhibitors
Macrolides
Cimetidine
Azoles (e.g. Itraconazole, Fluconazole)
Substrates
Warfarin
Carbamazepine, Phenytoin, Phenobarbitone
Oral contraceptive
Statin
Benzodiazepines, especially Midazolam
Ergot alkaloids
Calcium channel blockers
 When prescribing other drugs with antiretrovirals it is important to check for
interactions.
 In some cases the combinations are contraindicated (e.g. ergotamine and
PI’s) and in others dose adjustments are required (e.g. Warfarin and
Nevirapine guided by INR).
 The interactions may be bi-directional, for example carbamazepine and
nevirapine may reduce each others levels.
A useful source of HAART drug interaction information is or the University of
Cape Town Medicines Information Centre (021-4066829).


Other drug combinations share toxicities and should not be used together, for
example acyclovir and AZT because both drugs are bone marrow
suppressants.
Traditional remedies, phytotherapeutics, as well as other complimentary
medicines, when used together with HAART, could cause liver enzyme
induction or inhibition. They could also bind the drug in the gut, leading to
decreased blood levels of HAART drugs and ultimately resistance.
Table 13 shows examples of drugs that should be avoided when administered with
efavirenz, nevirapine, lopinavir/ritonavir or all 3 drugs.
55
N.B. Beware of other drug interactions that may require dosage adjustment (i.e.
anticonvulsant, psychiatric, anti-infective, cholesterol lowering drugs etc.). Seek
expert advice if your patient is taking one of these drug combinations.
Table 15: Prohibited drug combinations with specific HAART
Agent by class
Agents prohibited
with lopinavir/
ritonavir
Anti-arrhythmic agents Fleicanide
Propafenone
Anti-histaminics
Astemizole
Terfenadine
Agents prohibited
with ritonavir
Amiodarone
Fleicanide
Propafenone
Quinidine
Astemizone
Terfenadine
Anti-infectives
Cholesterol
lowering Simvastatin
agents
GI motility
Cisapride
Cisapride
Psychiatric medications St.
John’s
Wort
(Hypericum perforatum)
Sedative/hypnotics
Midazolam
Midazolam
Triazolam
Triazolam
Other
Dihydroergotamine
Pimozide
Ergonovine
Ergot derivatives
Ergotamine
Disulfiram
Metronidazole
Agents prohibited with
NVP and EFV
Astemizone
Terfenadine
Systemic Ketoconazole
Cisapride
St.
John’s
Wort
(Hypericum perforatum)
Midazolam
Triazolam
Dihydroergotamine
Ergotamine
Methylergonovine
5. SUBSTITUTES FOR INTOLERANCE IN ADULTS
All switches should be made by a doctor trained in HAART.
6. IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME (IRIS)





A rapid reduction in HIV viral load and a rise in CD4 count may occur after
HAART is commenced in patients with advanced HIV disease, particularly those
with a CD4 count < 50 cell mm3
This is accompanied by a restoration of pathogen specific immunity.
Inflammatory reactions in the first three months after starting HAART may
result as a consequence of the recovering immune system which may be
dysregulated.
This is termed IRIS. This is often in response to a high burden of microbial
antigen related to an OI that was present prior to HAART.
Before diagnosing IRIS it is important to exclude other possible explanations for
clinical deterioration such as:
o drug resistance to the treatment for the OI (especially MDR-TB)
o drug reactions
o additional bacterial
o Opportunistic infections.
56








Forms of IRIS are described as:
o “Unmasking” IRIS – this describes an inflammatory and often atypical
presentation of an OI soon after starting HAART that was untreated prior
to HAART commencement
o Paradoxical reactions – patients experience recurrence or worsening of OI
symptoms and signs after starting HAART despite being on appropriate
treatment for the OI. The reaction here is thought to result from an
immune response directed towards residual antigen
o Sarcoidosis and auto-immune diseases (e.g. Grave’s disease is described
as an IRIS phenomenon)
Kaposi’s sarcoma may worsen with an increase in lesions or inflammation of
existing lesions in 5% of patients (most KS lesions regress on HAART)
IRIS may result from reactions to inert foreign materials (e.g. tattoos)
IRIS most commonly occurs in association with OIs such as TB, cryptococossis,
MAC, CMV and HBV.
An example of a CMV unmasking IRIS is a patient presenting with an
inflammatory CMV uveitis after starting HAART.
TB paradoxical reactions are seen in up to 45% of patients starting HAART
while on TB treatment manifesting as:
o recurrence of fever and
o TB symptoms
o enlarging lymphadenopathy
o recurrent pulmonary infiltrates
o Dermatological IRIS manifestations (e.g. flare of acne)
Exclude multi-drug resistance in these cases.
IRIS is not indicative of drug failure or side effects.
IRIS is not a reason to stop HAART, or to change the highly active antiretroviral
regimen.
Management
o
o
o
o
o
o
Diagnosing the OI
exclude additional OI’s
Exclude antimicrobial resistance.
Continue HAART
Start and / or continue effective OI therapy
Consider steroids (eg. prednisone 1mg/kg, duration dependent on
response) in severe cases
o Stop HAART if the reaction is life threatening (e.g. CNS involvement)
and not responding to steroids.
57
SECTION 5: MANAGEMENT OF OPPORTUNISTIC
DISEASES IN HIV POSITIVE ADULTS
1. GENERAL PRINCIPLES
 HIV causes immune system damage through various mechanisms.
 The rate at which the disease progresses differs from individual to indvidual.
 Treatment for HIV & AIDS as well as any opportunistic infections needs to be
done in the context of treating the patient in a holistic manner, taking into
account the micro- and macro-nutritional status of the patient, assisting the
patient with the means to address this.
2. HIV COMPLICATIONS ANTICIPATED AT VARIOUS DEGREES OF
IMMUNOSUPPRESSION
CD4 count
3
>500cells /mm
200 – 500cells/mm3
Infectious complications
Non-infectious complications
Acute retroviral syndrome
Candidal vaginitis
Persistent generalized
lymphadenopathy (PGL)
Guillain-Barré syndrome
Myopathy Aseptic meningitis
Cervical intraepithelial neoplasia
Cervical cancer B-cell lymphoma
Anemia Mononeuronal multiplex
Idiopathic thrombocytopenic
purpura Hodgkin’s lymphoma
Lymphocytic interstitial
pneumonitis
Pneumococcal and other bacterial
pneumoniae
Pulmonary TB
Herpes zoster
Thrush
Candidal oesophagitis
Cryptosporidiosis
self-limited Kaposi’s sarcoma
Oral hairy leukoplakia
<200cells /mm3
P. jiroveci pneumonia
Wasting Peripheral neuropathy
Disseminated/chronic Herpes
HIV-associated dementia CNS
simplex Toxoplasmosis
lymphoma Cardiomyopathy
Cryptococcosis
Vacuolar myelopathy Progressive
Disseminated histoplasmosis and polyradiculopathy Immunoblastic
coccidioidomycosis
lymphoma
Cryptosporidiosis, chronic
Microsporidiosis
Miliary/extrapulmonary TB
Progressive multifocal
leukoencephalopathy (PML)
Candidal esophagitis
<50cells /mm3
Disseminated CMV Disseminated
M. avium complex
* Most complications occur with increased frequency at lower CD4 counts. Some conditions listed as
“Noninfectious” are probably associated with transmissible microbes: examples are lymphoma (EBV) and
cervical cancer (HPV).
58
3. RECOMMENDED PREVENTION OF OPPORTUNISTIC INFECTIONS IN
HIV POSITIVE ADULTS
Agent/intervention
Dosage/schedule
Indication
Disease prevented
TrimethoprimSulfamethoxazole
(TMP-SMX also known
as Co-trimoxazole or
Bactrim ® or Septran ®)
2 single strength
(80/400mg) po daily for
life or 1 double strength
tablet (160/ 800 mg) po
daily for life or 1 single
strength tablet (80/400
mg) po daily for life
(which is better tolerated
by some but is not
effective as prophylaxis
for toxoplasmosis)
Pneumocystis carinii
pneumonia,
toxoplasmosis, bacterial
pneumonia, diarrhoea
PAP smear
At first presentation and
annually thereafter.
HPV vaccine has the
greatest benefit when it
is given before a person
becomes sexually active,
thus their use in positive
women is under
investigation.1
0.5 mL IM injection x 3
doses according to
manufacturer’s
instructions, given to
well patients not needing
HAART. Where patients
are ill, vaccinate only
once on HAART and are
well
0.5 mL IM injection
annually prior to the
influenza season for
patients who are well
and not need HAART.
Where patients are ill,
vaccinate only once on
HAART and are well
All symptomatic HIV
positive individuals
(WHO clinical stage 2, 3
or 4) or CD4 count
below 250 cells / mm3 or
if there has already been
an active infection of
PCP, or HIV associated
thrush, unexplained
fever x2 weeks or
Toxoplasmosis.
Treatment no longer
needed once patient is
on HAART and their
CD4 >250 for 6 months
All HIV positive women
Hepatitis B vaccine
Influenza vaccine
All susceptible (HBc or
Hep BsAb negative)
HIV positive individuals
All HIV positive
individuals. (The use of
this vaccine in severely
immunocompromised
patients is not
recommended)
To detect human
papillomavirusassociated genital
epithelial cancersabnormal PAP smear
results should be
followed up in
accordance with current
accepted best practices.
Hepatitis B
Influenza
1 Nam publication, Derek Thaczuk, Thursday, December 14, 2006;
AIDS:Volume 20(18)28 November 2006p 2381-2383
59
3.1 Prevention of Pneumocystis jiroveci pneumonia (PCP)
Note: Shaded sections are interventions that are recommended at primary care
level.
Comments /
Condition
Management
Indications
Rationale
Primary Prophylaxis for
PCP
Trimethoprim/sulphamet
hoxazole (TMP-SMX
single strength 80/400
mg) 2 tablets po daily
for life or TMP-SMX
double-strength
(160/800 mg) 1 tablet po
daily for life or TMPSMX 1 single-strength
tablet po daily for life
(which is better tolerated
by some but is not
effective as prophylaxis
for toxoplasmosis).
Adults and adolescents
who are HIV positive
(including pregnant
women and those on
HAART) with:
• Symptomatic HIV
disease (WHO clinical
stage 2, 3 or 4)
• CD4 count less than
250 cells/ mm3
• or if there has already
been an active infection
with Pneumocystis
Prophylaxis for PCP in
individuals who are
sensitive to TMP-SMX
Consider re-introduction
of TMP-SMX, if
feasible (see note)
Alternative Dapsone
100mg po daily
Dapsone 50mg/day plus
pyrimethamine
50mg/week plus
leucovorin 25mg/week
Atovaquone 1500mg
POqd with meals2
As above
TMP-SMX at a dose of
one double-strength
tablet per day confers
cross-protection against
toxoplasmosis and some
common respiratory
bacterial infections.
Intolerance to TMPSMX is experienced by
25-50%, mostly as skin
rashes ± fever.
Secondary prophylaxis
Chronic maintenance
therapy should be
continued after treating a
confirmed episode of
PCP using the same
protocol as for primary
prophylaxis, except this
should only be
discontinued once the
patient has a CD4>250
for 6 months while on
HAART.
For patients who have an
adverse reaction that is
not life-threatening,
treatment with TMPSMX should be
continued if clinically
feasible; for those who
have discontinued such
therapy because of an
adverse reaction,
reinstitution of
TMPSMX should be
strongly considered after
the adverse event has
resolved. Patients who
have experienced
adverse events,
especially fever and
rash, might better
tolerate reintroduction of
the drug with a gradual
2 Bartlett JG and Gallant JE Medical Management of HIV Infection 2005-2006 pg 50. Suggested
regimens not available in public sector.
60
Condition
Discontinuation of
Primary Prophylaxis for
PCP
Restarting Primary
Prophylaxis for PCP
Management
Indications
Once patients are on
HAART and their CD4
> 200cells/mm3 for 6
months
It may be possible to
discontinue prophylaxis
when patients have
sustained a CD4 count
of greater than 250 cells
/ mm 3 for at least 3-6
months
As for Primary
Prophylaxis
recommendations.
As for Primary
Prophylaxis
recommendations.
PCP Prophylaxis for
Pregnant Women
As for other adults.
Condition
Primary Prophylaxis for
Toxoplasma encephalitis
(TE)
Management
Advise against eating
undercooked meats,
about safe food handling
procedures and
appropriate pet care for
cats Trimethoprim/
sulphamethoxazole
(TMP-SMX single
strength 80/400 mg) 2
tablets po daily or TMPSMX 1 double-strength
tablet po daily
Indications
Toxoplasma seropositive
adults and adolescents
who are HIV positive
(including pregnant
women and those on
HAART) with CD4
count less than 100
cells/ mm3 who are not
taking PCP Prophylaxis
with a double strength
TMP-SMX dosage.
Comments /
Rationale
increase in dose
(desensitization) or
reintroduction of TMPSMX at a reduced dose
or frequency; up to 70%
of patients can tolerate
reinstitution of therapy
in this way. Beware of
severe SJ reaction. Do
not re expose these
patients.
Mostly advised when
discontinuation of
primary prophylaxis (no
prior episode of PCP) is
considered for
individuals on HAART
who meet the criteria
described.
No data available to
demonstrate that this
should differ from
primary prophylaxis.
TMP-SMX may
exacerbate folate
deficiency and increase
the risk of neural tube
defects. For this reason,
pregnant women should
preferably be given
TMP-SMX after the first
trimester and should also
receive folate
supplements.
Comments / Rationale
The double strength
TMP-SMX regimens
advised for PCP
Prophylaxis are also
effective against
Toxoplasma. Individuals
who do not know their
Toxoplasma serology
status, or are
seronegative, who are
not taking a PCP
prophylactic regimen
known to be active
61
Condition
Management
Indications
Prophylaxis for
Toxoplasma in
individuals who are
sensitive to TMPSMX
Non-drug measures, as
above.
Dapsone 50mg po daily
(± pyrimethamine 50 mg
po weekly) plus
leucovorin 25mg/week.
Adults and adolescents
who are HIV positive
(including pregnant
women and those on
HAART) with CD4
count less than 100 cell /
mm3 and are
Toxoplasma
seropositive.
Discontinuation of
Primary Prophylaxis for
Toxoplasmosis
discontinuing
prophylaxis for patients
as per guidelines for
PCP
Pregnant HIV positive
women who have
evidence of prior
Toxoplasma exposure
can be administered
TMP-SMX for
prophylaxis against TE
as described for PCP.
Treat with Amphotericin
B 1mg/kg/dose ivi in
dextrose for 2 weeks
followed by fluconazole
400mg po daily x
8weeks and then
fluconazole 200mg/day
for life or until
CD4>250cells/mm3
Toxoplasma Prophylaxis
for Pregnant Women
Cryptococcosis
HAART is critical
Primary prophylaxis is
indicated for special
cases only: CD4 count
less than 50 cells / mm3
with unusually high
additional risk of
Cryptococcosis, or if
considered as part of the
Comments / Rationale
against TE should be
retested for IgG antibody
to Toxoplasma when
their CD4 count declines
below 100 cell/ mm3 to
determine whether they
have seroconverted and
are therefore at risk for
TE. Secondary
Prophylaxis Individuals
who have had TE should
be administered lifelong
suppressive therapy
(secondary prophylaxis /
chronic maintenance
therapy) with drugs
active against
Toxoplasma to prevent
relapses.
Prophylactic
monotherapy with
dapsone, pyrimethamine,
azithromycin, or
clarithromycin cannot be
recommended on the
basis of current data. It
is advisable to check
Toxoplasma serology in
these patients to guide
therapy. Prophylaxis for
PCP should continue if it
is still indicated.
NB: Primary toxoplasma
infection or active
toxoplasmosis (including
TE) should be evaluated
and managed during
pregnancy in
consultation with
appropriate experts.
Fluconazole and
Itraconazole should be
avoided in pregnancy
and effective birth
control measures should
be recommended to all
HIV positive women on
prolonged azole therapy.
62
Condition
Mycobacterium
tuberculosis Isoniazid
Preventive Therapy (I
PT)
Herpes Simplex Virus
(genital or orolabial)
Varicella-Zoster Virus
(VZV)
Human Papilloma virus
Infection
Management
>6months on HAART
(total of 12 months
fluconazole)
Management of raised
intracranial pressure
(>20cmCSF) is through
the draining of 20-30ml
of CSF prn to reduce
opening pressure by
50%). Daily LPs may be
required
When indicated:
Isoniazid 5 mg/kg daily
is to be given for 6
months + pyridoxine
50mg po daily for 6
months.
Indications
decision to treat other
concomitant fungal
infections.
Comments / Rationale
HIV positive adults with
no signs or symptoms of
TB and a normal chest
x-ray. Tuberculin skin
test-positive patients
show greater benefit. It
is extremely important to
rule out active TB before
initiating I PT to prevent
the development of
isoniazid resistance.
The feasibility of
providing I PT in TB
prevention is of proven
value in low income
countries in individuals
at a risk due to
conditions like HIV and
for health workers. For
more information about I
PT see Appendix 2 / 3 /
4 below.
Primary infection can be
prevented through safer
sex (condom usage) at
all times and specific
avoidance of contact
with herpetic lesions
(genital or orolabial).
Drug prophylaxis of
initial episodes of HSV
disease is not
recommended.
Individuals who have no
history of chickenpox or
shingles, or seronegative
for VZV should avoid
exposure to persons who
are infected with
chickenpox or shingles.
Prevent exposure: safer
sex practices (use of
condom at all times)
should be advised.
Prevention of HPVassociated Genital
Epithelial Cancers in
Individuals with
frequent or severe
recurrences can be
administered daily
suppressive therapy with
oral acyclovir 400mg bid
or famciclovir 250mg
bid or valacyclovir 0.51gqd3.
All HIV positive women
Pregnant women: VZIG
(Varicella Zoster
Immune Globulin) 125U
per 10kg up to 625U IM
is recommended for
VZV-susceptible,
HIVpositive pregnant
women within 96 hours
after exposure to VZV.
Abnormal PAP smear
results should be
followed up in
accordance with current
accepted best practices.
3 These drugs are all clinically equivalent Br J Dermatol 2001;144:188
63
Condition
Influenza Virus
Hepatitis B Virus
Management
Indications
HIV positive Women:
Pelvic examination and a
Pap smear at first
presentation and
annually thereafter if this
is normal.
Influenza vaccine 0.5ml All HIV positive
intramuscularly annually individuals annually
prior to the Influenza
season. (The use of this
vaccine in severely
immuno-compromised
patients is not
recommended)
Hepatitis B Vaccine 0.5
All susceptible (AntimL IM injection X 3
HBc and HepBs Ab
doses according to
negative) HIV positive
manufacturer’s
individuals. (The use of
instructions.
this vaccine in severely
immunocompromised
patients is not
recommended)
Comments / Rationale
Amantadine 100mg po
twice a day is an
alternative for selected
susceptible
(unimmunised)
individuals who are
acutely exposed to
Influenza.
64
4. MANAGEMENT OF OPPORTUNISTIC INFECTIONS IN HIV POSITIVE
ADULTS
4.1 Management of common respiratory infections associated with HIV
Condition
Recommended treatment
Comments
Community acquired Pneumonia
Exclude PCP and active
pulmonary TB. In many cases,
empirical therapy needs to be
started, pending the results of
investigations. Severe infections
require hospitalisation for
Parenteral antibiotics and
supportive therapy (Bed rest,
oxygen, IV fluids and nutrition)
Frequent monitoring of
temperature, blood pressure,
respiratory and pulse rates in order
to detect complications early and
to monitor response to therapy.
CXR and pre-treatment cultures of
blood and sputum are required.
Treatment of specific organism is
ultimately guided by the results of
investigations and culture
sensitivities, as well as clinical
response to first-line treatment.
Initiating treatment is with
Ceftriaxone 1g ivi bid. Changed to
Amoxycillin 500mg pO tid once
the fever has settled. Antibiotics
are given for 2 weeks in total.
‘Usual’ pneumonia pathogens
suspected (S. pneumoniae / H.
influenzae)
Oral: Amoxicillin 250-500mg 8
hourly until infection resolves.
Duration of antibiotic therapy is
guided by clinical response, but
should not be less than 7–10 days.
Where there is likely
Penicillin/Ampicillin resistance:
Amoxicillin/clavulanic acid (eg
Augmentin®) 250/125 mg (375
mg tablet) po 8 hourly should be
first choice Penicillin allergic
patients: Erythromycin 500mg po
6 hourly Parenteral antibiotic
therapy Depends on the causative
organism. Empirical treatment
Severe infections are suggested
when there is: Moderate/severe
respiratory distress; fever higher
than 39.50C; hypoxia; confusion;
dehydration; hypotension; heart
rate >120; extensive pneumonia
(bilateral / more than 1 lobe
involved on CXR) or
complicated pneumonia (such as
empyema). Blood cultures need
to be done. A control post
treatment chest X-ray is always
indicated to ensure complete
resolution of the pneumonia.
With an uncomplicated clinical
course this should only be done
after 4–6 weeks, as radiological
resolution may be delayed.
Follow-up X-rays are indicated
earlier only when complications
are suspected (e.g. empyema,
abscess or pneumothorax). At the
onset of the pneumonia the X-ray
changes may be unimpressive,
and may only develop fully after
a few days. Prolonged fever and
clinical signs may be due to any
of the complications, to the
incorrect choice of antibiotic, or
due to an underlying bronchus
obstruction (foreign body or
carcinoma). These patients
should be further investigated.
Common at all stages of HIV
infection. Clinically lobar or
bronchopneumonia ± effusion.
Penicillin/Ampicillin resistance is
increasing, so alternative
treatment might be required.
65
Condition
Recommended treatment
Suspected ‘atypical’ pneumonia
(Mycoplasma/ Legionella)
could be started with Benzyl
penicillin, IV, 2 MU 6 hourly for
10 days (or combination therapy
with Gentamicin IV, if a gram
negative infection is suspected; or
an appropriate Cephalosporin)
Erythromycin 500mg po 6 hourly
for 10-14 days.
Comments
4.2 Treatment of Pneumocystis jiroveci pneuomonia (PCP)
Condition
Recommended treatment
Comments
Acute PCP Infection
Trimethoprim/sulphamethoxazole,
20/100 mg/ kg/day in 4 divided doses
equivalent to Co-trimoxazole
1tab/4kg body weight /day in 3 to 4
doses (max of 16tabs/d). The
duration of treatment is 21 days,
followed by 2 tablets daily for life or
until CD4>250cells/mm3 for >6m
when on HAART. If at all possible,
this should be given orally.
IV Trimethoprim/sulphamethoxazole
may be used in patients not able to
swallow.
Hypoxic patients
Prednisone, 40 mg 12hourly for 5
days, followed by 40mg daily for 5
days and then 20mg for 11 days
PCP often presents as an acute/sub-acute
non-productive cough, fever with 1-2
weeks dyspnoea, marked respiratory
distress. Diagnosis further suggested by:
CD4 < 250 cell / mm3; normal-looking X
ray in early stages, or ‘ground-glass’
interstitial infiltrates and other atypical
radiological findings; Relative hypoxia
(p02 <10) on ABG or desaturation on
exercise (if sats are normal at rest, check
patienst sats with a sats probe before and
after a 30m walk or less if the patient
reaches maximum heart rate- a drop of
more than 5% is significant
Diagnosis is usually made empirically but
can be confirmed with a DFAT on induced
sputum
Moderately severe or severe disease is
present when the patient is hypoxic
(pO2<10). Steroid therapy can further
compromise the individual’s immunity and
other opportunistic infections (such as
Candidiasis, TB, CMV and Herpes) should
be anticipated.
Patients intolerant to
Trimethoprim/
Sulphamethoxazole
Trimethoprim 300mg 8hourly +
dapsone 100mg daily or
Clindamycin 450 mg po 8 hourly
plus primaquine 15mg po daily
(exclude G6PD deficiency when
giving primaquine) (atovaquone can
be substituted)
66
4.3 Management of common oral and oesophageal conditions associated with HIV
Condition
Recommended treatment
Comments
Candidiasis (Thrush) Oropharyngeal
Milder topical forms
Nystatin lozenges 100 000 IU, to be
sucked 4 times daily or Nystatin 100
000 IU/mL 1-2 mL 4 times daily for
10 days If no improvement after 2
weeks, nystatin can be replaced with:
Miconazole 2% oral gel twice daily
for 10 days or Amphotericin B
lozenges 10 mg suck 1 slowly 4
times daily, up to 8 lozenges in
severe cases .Where there is
retrosternal odynophagia treat with
fluconazole 200mg daily for 2 weeks
Fluconazole 200mg po daily for 5-14
days. As a secondary option:
Ketoconazole, oral, 150mg- 400mg
po daily for at least 14 days or
Itraconazole 200mg po daily for 14
days For patients who cannot take
oral medications: Fluconazole 200mg
IV daily for 5-14 days.
Chlorhexidine gluconate 0.2%
mouthwash may be used for
secondary infections.
HAART is recommended to be
commenced as soon as patient is
stable to ensure recovery of natural
immunity that will prevent recurrence
Oesophageal or invasive candidiasis
Severe or recurrent
Aphthous ulcers
Oral hairy leukoplakia
Gingivitis/ periodontitis
Topical steroids such as
hydrocortisone cream 1% or
Kenalog® in Orabase® or a steroid
inhaler such as beclomethasone or
budesonide applied directly to the
lesions or Tetracycline 250 mg tablet
dissolved in water 4 times daily
Severe or refractory cases, including
oesophageal ulcers: Prednisone 40
mg po daily for 1-2 wks, then reduce
incrementally
This usually does not require
treatment – if symptomatic in
selected cases: Acyclovir 800 mg po
5 times a day for 2-3 wks or
valaciclovir 1g 8hrly x 28days gives
temporary respite.
Curettage and debridement of
involved tissue + topical antiseptic
such as povidine-iodine solution and
chlorhexidine mouth rinses. Selected
cases: Metronidazole 200mg three
times a day or 400 mg po twice a day
for 7-14 days or clindamycin 300 mg
three times a day for 7-14 days.
WHO has recommended that
fluconazole should replace
ketoconazole as the prototype drug
since it is more cost-effective and is
associated with fewer adverse effects.
Referral to a specialist centre may be
required. Patients should be worked
up for HAART to ensure treatment
initiation as a matter of urgency
Consider discontinuing any
medications that might be causing the
ulcers. Where patients are on the
standard HAART regimens, treat
ulcers symptomatically. This might
be an IRIS4 as a consequence of
HAART initiation in severely
immune compromised patients and
might need to be biopsied in
refractory cases
Most lesions are asymptomatic and
do not require therapy. Most treated
cases relapse and may require
maintenance high-dose acyclovir if
problematic. OHL is a sign that the
patient may have a low CD4 count
often <200c/ml and should be
worked up for HAARTdespite the
often appearance of being well
Four clinical phases are described:
gingival erythema, necrotizing
gingivitis, necrotizing peridontitis,
and necrotizing stomatitis Usual
presenting complaints are oral pain
and bleeding.
4 IRIS is Immune reconstitution inflammatory syndrome often seen in patients with CD4<50 cells/mm 3
within a few weeks of commencing HAART. They present with either new illnesses or exacerbation of
diseases they are currently receiving treatment for like TB, CMV, KS, NHL, MAC etc
67
4.4. Management of common skin conditions associated with HIV
HIV positive patients are more prone to a wide variety of skin problems. Conditions that
usually occur in non-HIV infected individuals should generally be managed in the same
way, in accordance with Standard Treatment Guidelines.
Condition
Recommended treatment
Comments
Molluscum contagiosum
Topical application of tincture of
iodine or 1% phenol to individual
lesions or Cryotherapy with liquid
nitrogen or Surgical excision /
curettage or electrosurgery. Skin
biopsy might be required to rule
out cryptococcal skin rash or
cutaneous lymphoma in cases
where the clinical picture is
unclear
For extensive lesions, which
usually indicate severe
immunodeficiency and are too
widespread for topical treatment,
systemic retinoid may be
effective. This requires specialist
supervision. The best outcomes
are seen when patients are started
on HAART. Response then to the
standard treatments improve and
recurrence slows eventually
disappearing over time as the
immune system strengthens
Seborrhoea
Skin Steroid cream
(hydrocortisone 1%) and/or
topical azole cream (e.g.
Miconazole 2% cream), or
Terbinafine cream, applied twice
a day Scalp 2% selenium sulphide
suspension - apply weekly by
lathering on scalp and rinse off
after 10 minutes or Shampoos
(e.g. Selsun® Head and
Shoulders®, Gill shampoo®)
containing selenium sulfide, zinc
pyrithiore, ketoconazole, salicylic
acid or coal tar, used daily.
Folliculitis (including S. Aureus;
Eosinophilic inflammation;
Pityrosporum ovale)
Depends on aetiology
Staphylococcal folliculitis:
Topical cleansing with antiseptic
lotions (e.g. chlorhexidine
gluconate 2% or Hibiscrub®);
Topical 2% sulphur cream twice a
day. Consider short course
antibiotic therapy: Flucloxacillin
500 mg po four times a day for 10
days In pregnant and/or
penicillin-allergic patients:
Erythromycin 500 mg 4 times
daily for 10 days Recurrent
disease: chronic antibiotic
(clindamycin 150 mg four times a
day or TMP-SMX 1 DS four
times a day)+/-nasal mupirocin
Fungal: Miconazole 2% cream
applied twice daily or other
topical antifungal or systemic
A group of acne-like conditions
that present as pruritic follicular
papules and pustules on face,
trunk and extremities at lower
CD4 counts. Spontaneous
remissions and exacerbations
occur. This is a strong indication
to commence ART even in cases
where the CD4>250
68
Condition
Recommended treatment
Comments
antifungal agents Eosinophilic:
Topical steroids and anti-pruritics
(such as promethazine or
hydroxyzine) Phototherapy with
UVB and/or PUVA is sometimes
effective.
Fungal skin / nail infections
Skin: 6% benzoic acid and 3%
salicylic acid ointment twice daily
for 4 weeks or 2% miconazole
cream applied topically twice
daily for 4 wks or other topical
antifungal agents such as
clotrimazole For severe nail
infections, consider: itraconazole
400 mg po daily for 7 days
repeated monthly x 2 months
(fingernails) and 3 months
(toenails); fluconazole 200mg
weekly for three months for
finger nails and 6 months for
toenails.
Where infections are persistent or
severe consider commencing
HAART
Drug-related skin reactions
Depends on severity and the need
for the implicated drug.
Discontinue suspected drug.
Antihistamines such as
chlorpheniramine 4 mg po 3-4
times daily ± topical steroids such
as hydrocortisone 1% cream
applied twice daily. Severe
reactions: discontinue all drugs.
Systemic steroids are not useful.
Morbilliform exanthema are more
common; most frequent onset 710 days after starting new drug.
Diagnosis on basis of clinical
features, past history of drug
eruptions and history of new drug
exposure. Response to stopping
drug should be noticed within 3-5
days. It may be possible to reintroduce the drug, if necessary, if
the reaction was not severe.
Nevirapine and cotrimoxazole are
the commonest causative agents
where these are used but reactions
to efavirenz are not uncommon,
often not as severe. Most cases
can be treated symptomatically
but ARV drugs might need to be
changed where symptoms worsen
or where there is involvement of
conjunctiva and mucous
membranes
69
Condition
Recommended treatment
Comments
Psoriasis
Salicylic acid 2% in white soft
paraffin 3 times daily to local
plaques or other topical
treatments with emollients,
topical steroids, coal tar, vitamin
A, vitamin D derivatives, salicylic
acid. Phototherapy.
Avoid methotrexate and
prednisone.
Kaposi’s sarcoma
If HIV positive commence
HAART, despite CD4 count.
Investigate for other OIs
especially TB. Patients need to be
referred to a treatment centre
where treatments will be
individualized based on the extent
of disease, rate of growth,
symptoms, CD4 count and
general health. Local therapy can
be used for small skin and oral
lesions which include
intralesional chemotherapy
(vinblastine), local radiotherapy,
liquid nitrogen cryotherapy or
topical aliretinoin 0.1%gel.
Cytotoxic chemotherapy for
extensive disease is recommended
where;
Multiple skin lesions
Progressive disease
Visceral involvement
Extensive oedema
B symptoms (fever, night sweats,
significant constitutional
symptoms
Failure to respond to local therapy
and HAART
Treatments should be performed
at a site where there is the
capacity to manage this disease.
HAART should be commenced
even before chemotherapy as this
improved response to
chemotherapy. Where lesions
increase on HAART (IRIS)
continue on HAART with
ongoing chemotherapy
4.5 Treatment of herpes virus infections
Condition
Herpes simplex virus (HSV)
Initial treatment of mild skin or
genital HSV
Recommended treatment
Aciclovir 400 mg po 3 times a
day or Famciclovir 250 mg po
3 times daily or Valaciclovir 1
gm po twice a day All
administered for 7-10 days
Comments
Herpes is a recurrent viral
disease that has no cure. Two
serotypes of HSV have been
identified: HSV-1 and HSV-2.
Most cases of recurrent genital
herpes are caused by HSV-2.
Genital herpes is a sexually
transmitted disease. Antivirals
do not cure the infection or
prevent transmission. These
drugs may shorten the time to
70
Condition
Recommended treatment
Comments
clinical remission.
Recurrent HSV
Aciclovir 400 mg po three
times a day or 800 mg po twice
a day or Famciclovir 125 mg
po twice daily or Valaciclovir
500 mg po twice daily All
administered for 5 days.
Early treatment of initial
infections is much more
effective than treating recurrent
infections. Most patients with
first episode genital HSV-2
infection will have recurrent
episodes of genital lesions.
Initiate therapy at first sign of
prodrome or genital lesions.
Relapses after treatment of
acyclovir-resistant strains often
involve acyclovir-sensitive
strains.
Severe or refractory HSV
Infection
Consider Aciclovir 5-10 mg/kg
IV 8 hourly infused over 1 hour
for 5-7 days or Aciclovir 400-800
mg po 5 times a day for 7-14 days
or Valaciclovir 1 gm po 3 times a
day for 7-14 days
Varicella zoster virus (VZV)/
Shingles
Aciclovir 800 mg po 5x/day at
least 7 days (until lesions crust) or
Famciclovir 250 mg po tid or
Valaciclovir 1 gm po tid
Dermatomal VZV
Acyclovir 800 mg po 5x/day at
least 7 days (until lesions crust) or
Famciclovir 250 mg po tid or
Valaciclovir 1 gm po tid
Disseminated, opthalmic nerve
involvement, corneal or visceral
infection (life or vision
threatening) VZV
Acyclovir, IV, 5-10 mg/kg over 1
hour at 8 hourly intervals for at
least 7 days or Foscarnet 40
mg/kg IV 8 hourly or 60 mg/kg
12 hourly. For corneal disease in
addition to parenteral (IV
therapy): Topical acyclovir eye
• If failing to respond, or for
disseminated HSV, give aciclovir
30 mg/kg/day IV and test
sensitivity of isolate to acyclovir;
• Resistant HSV: foscarnet 40
mg/kg IV 8 hourly, topical
trifluridine, oral valaciclovir, or
high-dose IV aciclovir (12-15
mg/kg IV 8 hourly or by
continuous infusion).
VZV infections in
immunocompromised patients
should be treated with appropriate
anti-viral drugs. However drug
therapy is expensive and unlikely
to be of advantage to patients with
lesions that have healed (crusted
phase). VZV also seen in patients
well and stable on HAART and
does not indicate a failing
regimen. Treatment is the same
• Treatment can be started long as
new lesions are forming •
Postherpetic neuralgia is less
common in young patients • No
maintenance therapy is
recommended • Antiviral therapy
has not been shown to be
effective beyond 7 days of acute
therapy
To be prescribed by a specialist
only. The dose must be adjusted
according to renal function.
71
Condition
Recommended treatment
Comments
drops 3% ointment, 4 hourly for
14 days. For VZV pneumonia
consider adding: Hydrocortisone
200 mg IV 6 hourly for 7 days.
Pain control Acute phase of
infection
Ibuprofen 400 mg po 3 times
daily or Paracetamol 1 000 mg po
(4–6 hourly) plus Amitriptyline
25–50-75 mg po at night.
Chronic management of Zoster
Associated Pain
Amitriptyline 25-50-75 mg po at
night +/- Carbamazepine 100-400
mg po twice daily.
Pain is often very severe and
requires active control usually
with a combination of
nonsteroidal, opiate analgesics
and amitriptyline.
If pain remains severe after 4
weeks, refer.
4.6 Management of human papillomavirus infection
Condition
Recommended treatment
Comments
Non-drug treatment
Surgical removal - tangential
scissor excision, tangential shave
excision, curettage, or
electrosurgery. Or Cryotherapy
with liquid nitrogen or cryoprobe.
Repeat applications every one to
two weeks
Drug Treatment for warts in
general
Podophyllin resin 10–25% in
compound tincture of benzoin. A
small amount should be applied to
each wart and allowed to dry. To
avoid the possibility of problems
with systemic absorption and
toxicity, some experts recommend
that application be limited to <0.5
mL of podophyllin or <10 cm2 of
warts per session. Repeat weekly
if necessary. or Trichloracetic
acid (TCA) or bichloracetic acid
(BCA) 80–90%. Apply a small
amount only to warts and allow to
dry, at which time a white
“frosting” develops; apply talc or
sodium bicarbonate to remove
unreacted acid if an excess
amount is applied. Repeat weekly
if necessary.
This is a sexually transmitted
disease. Note: The removal of
warts does not necessarily
decrease infectivity. It is
advisable to treat sexual partners
as well. Surgical removal of warts
has the advantage over other
modalities of rendering the patient
wart-free, usually with a single
visit. An expert should do this.
The use of podophyllin is
contraindicated during pregnancy.
Podophyllin is caustic and should
be used with care. Avoid contact
with healthy skin. After visible
genital warts have cleared,
follow-up is not mandatory. Reoccurrence is most frequent
during the first three months.
Patients should be warned that
scarring in the form of persistent
hypo-or hyperpigmentation is
common with ablative modalities.
Patients with severe cutaneous
HPV infections respond poorly to
these treatment modalities despite
in many cases being stable on
HAART.New treatments are
continually being developed
72
Vaginal warts
TCA or BCA 80–90% applied
only to warts. Apply a small
amount only to warts and allow to
dry at which time a white
“frosting” develops; apply talc or
sodium bicarbonate to remove
unreacted acid if an excess
amount is applied. Repeat weekly
if necessary. or Podophyllin 10–
25% in compound tincture of
benzoin applied to a treated area
that must be dry before removing
the speculum. Treat less than or
equal to 2 cm2 per session.
Repeat application at weekly
intervals.
Cervical warts
Urethral meatus warts
Anal warts
Oral warts
Podophyllin 10–25% in
compound tincture of benzoin.
The treatment area must be dry
before contact with normal
mucosa. Podophyllin must be
applied weekly if necessary. Or
Cryotherapy with liquid nitrogen
or cryoprobe.
TCA or BCA 80–90% applied to
warts. Apply a small amount only
to warts and allow to dry at which
time a white “frosting” develops;
apply talc or sodium bicarbonate
to remove unreacted acid if an
excess amount is applied. Repeat
weekly if necessary. or
Cryotherapy with liquid nitrogen
or surgical removal.
Cryotherapy with liquid nitrogen
or surgical removal.
The use of a cryoprobe in the
vagina is not recommended
because of the risk of vaginal
perforation and fistula formation.
Because of concern about
potential systemic absorption,
some experts caution against
vaginal application of
podophyllin. Podophyllin is
contraindicated during pregnancy.
For women with exophytic
cervical warts, a high-grade
squamous intraepithelial lesion
(SIL) must be excluded before
treatment is begun. Management
should be carried out in
consultation with an expert.
The use of podophyllin is
contraindicated in pregnancy. To
be performed by a specialist only.
Management of warts on rectal
mucosa should be referred to an
expert.
Management of warts should be
referred to an expert.
4.7 Management of genital and sexually transmitted conditions (please check
alignment with government syndromic management guidelines and let me know)
 Sexually transmitted infections in HIV positive individuals should be
managed syndromically following the Department of Health’s Protocols for
the management of a person with sexually transmitted diseases with the
following considerations:
o Urethral discharge – unchanged.
73
o Genital ulcers – if painful vesicular lesions, see ‘Treatment of herpes
virus infections’
o Vaginal discharge – unchanged but for vulvo-vaginal candidiasis
Condition
Genital Herpes Simplex Virus
Vulvo-vaginal Candidiasis
(Thrush)
Pelvic Inflammatory Disease
(PID)
Recommended treatment
See ‘Treatment of herpes virus
infections.
Clotrimazole vaginal tablets 100
mg or vaginal cream, nightly for
7–10 nights. For more severe
cases, use systemic therapy with
Fluconazole 150mg po x 1. As a
secondary option: Ketoconazole,
oral, 200-400 mg daily, for 5-7
days.
All patients with stage II-IV and
severely ill patients with stage I
must be hospitalised for
parenteral antibiotic therapy. All
patients must receive adequate
therapy for both gonococcal and
chlamydial infection.
Pelvic Inflammatory Disease
(PID) (Continued)
PID: Stage I Acute
(uncomplicated) salpingitis
Stage II Salpingitis + peritonitis
Ciprofloxacin 500 mg as a single
oral dose (Alternative to
ciprofloxacin: Ceftriaxone 250
mg IM single dose) plus
Doxycycline, 100 mg po 12
hourly (with meals) for 14 days
plus Metronidazole 400 mg po 12
hourly for 14 days.
Cefoxitin 2 g IV 6 hourly plus
Doxycycline 100 mg IV 12
Comments
More prolonged therapy may be
required in severely immunedeficient women. WHO has
recommended that fluconazole
should replace ketoconazole as
the prototype drug since it is more
cost-effective and is associated
with fewer adverse effects.
Consider early HAART initiation
in intractable cases.
Adequate fluid replacement,
analgesics and antipyretics should
be provided. Patients should be
tested for syphilis and other
STDs. In stage III, surgery is
indicated if the diagnosis is
uncertain, if rupture seems
imminent, if there is no adequate
response after 48 hours of
appropriate therapy, if the patient
deteriorates on treatment or if
after 4–6 weeks there still is a
large or symptomatic pelvic mass.
Contact tracing. Remember that
PID is usually sexually
transmitted and that sexual
partners should be offered
treatment for their own health and
to prevent re-infection and spread
of the infection to other partners.
Intra-uterine contraceptive
devices are a risk factor for PID
and should be removed after
commencement of antibiotic
therapy. Alternative contraceptive
choices should be offered.
Characterised clinically by local
adnexal tenderness, but no
peritoneal tenderness. As the
prevalence of resistant GC
increases, ceftriaxone is the
preferred treatment
Characterised clinically by local
adnexal tenderness and peritoneal
74
Condition
Stage III Tubal occlusion + pus +
distention
Stage IV Rupture to peritoneal
cavity
Recommended treatment
Comments
hourly plus Metronidazole, 400
mg po 12 hourly, if there is no
vomiting, otherwise per rectum
500 mg 8 hourly initially for 3-5
days. This regimen is given for at
least 48 hours after the patient
clinically improves. After
discharge from hospital, the
patient continues with oral
therapy with: Doxycycline 100
mg po 12 hourly plus
Metronidazole 400 mg po 12
hourly until a total of 14 days of
therapy has been completed.
Clindamycin 900 mg
intravenously 8 hourly plus
Gentamicin, IV, for at least 48
hours at a loading dose of 2
mg/kg, followed by 1.5 mg/kg 8
hourly This regimen is given for
at least 48 hours after the patient
clinically improves. After
discharge from hospital, the
patient continues with oral
therapy with: Doxycycline 100
mg orally 12 hourly plus
Metronidazole, oral, 400 mg 12
hourly until a total of 14 days of
therapy has been completed plus
Clindamycin 450 mg four times
daily until a total of 14 days of
therapy has been completed.
Antibiotics as stage III. Rapid
surgical exploratory laparotomy.
irritability (rebound, guarding,
etc) Contact tracing Remember
that PID is usually sexually
transmitted and that sexual
partners should be offered
treatment for their own health and
to prevent re-infection and spread
of the infection to other partners.
Characterised clinically by
peritonitis. Gentamicin therapy
should preferably be monitored
by blood drug levels in patients
with impaired renal function.
Contact tracing Remember that
PID is usually sexually
transmitted and that sexual
partners should be offered
treatment for their own health and
to prevent re-infection and spread
of the infection to other partners.
Characterized by septicaemia,
collapse. Contact tracing
Remember that PID is usually
sexually transmitted and that
sexual partners should be offered
treatment for their own health and
to prevent re-infection and spread
of the infection to other partners.
75
4.7.1 Treatment of Syphillis
Condition
Primary or secondary syphilis
Recommended treatment
Benzathine penicillin, IM, 2.4
MU as a single dose.
Early latent syphilis
Benzathine penicillin, IM, 2.4
MU as a single dose.
Benzathine penicillin, IM, 7.2
MU total, administered as 3 doses
of 2.4 MU each, at weekly
intervals Non-pregnant penicillinallergic patients: Doxycycline,
oral, 100 mg twice daily, for 2
weeks if duration of infection
<one year, otherwise, for 4 weeks,
with close follow-up.
Benzathine penicillin, IM, 7.2
MU total, administered as 3 doses
of 2.4 MU at weekly intervals.
Refer to text above
Late latent syphilis or latent
syphilis of unknown duration
Tertiary syphilis
Neurosyphilis
Comments
Parenteral benzyl penicillin is the
preferred drug for treatment of all
stages of syphilis. The
preparation(s) used (i.e.,
benzathine, aqueous procaine, or
aqueous crystalline), the dosage,
and the length of treatment
depend on the stage and clinical
manifestations of disease.
Parenteral benzyl penicillin is
effective in achieving local cure
(healing of lesions and prevention
of sexual transmission) and in
preventing late sequelae.
Follow-up serology tests for 6
months.
Pregnant patients with penicillin
allergy: see above.
4.8 Management of neurological complications associated with HIV
Condition
HIV-associated Dementia (HAD)
Myopathy (inflammatory)
Recommended treatment
Possible benefit from
antiretroviral regimens with
agents that penetrate the CNS
(AZT, d4T, ABC, nevirapine; less
penetration – efavirenz, ddI,
3TC,).
Consider discontinuing AZT for 3
weeks (if applicable). Nonsteroidal anti-inflammatory agents
sometimes useful. Prednisone 4060 mg/day (for severe case,
preferably with biopsy-proven
inflammation).
Comments
AZT at higher dose for mild or
moderately severe HAD has been
shown beneficial. Patients
respond to HAART. Monitor the
effectiveness of therapy with
neurocognitive tests.
Indication for treatment is
proximal muscle weakness plus
elevated creatine kinase. Often
unclear whether due to HIV or
AZT so consider changing
HAART and monitor clinical and
CPK response. Refer for expert
opinion
76
Peripheral neuropathy
Neuropathic pain can be difficult
to relieve. Consider Ibuprofen
400-800 mg po three times a day
plus Amitriptylline 25-50-75 mg
po at night or other tricyclic
antidepressants. Alternatives:
Carbamazepine 200-400 mg po
twice a day.
Peripheral neuropathy may be
HIV-related but it may also be a
side effect of several drugs such
as isoniazid, ddI, d4T and ddC. If
using Tricyclic antidepressants,
increase doses incrementally (eg.
Nortriptyline started at 10 mg at
night, increasing the dose by 10
mg every 5 days to maximum of
75 mg daily or 10-20 mg three
times a day until effective).
4.9 Management of psychiatric disorders in the presence of HIV
4.9.1 General Principles












Psychiatric disorders can occur prior to HIV infection, and may increase risk
for infection. Alternatively, people who have never experienced mental
illness may have the first onset as a complication of HIV infection, of
opportunistic infections and illness and HIV-related treatments.
Assess new onset major mental illness (a first episode) medically completely
including an HIV screen.
Rule out underlying physical cause when an exacerbation occurs even when
major mental illness is recurrent.
Refer patients for:
o management of acute psychosis and mania
o presence of dangerousness to self or others
o Inability to manage the psychiatric diagnosis in the primary case
setting.
Psychotropic medications are effective in the presence of HIV infection,
assuming urgent medical conditions have been addressed.
Do a complete medical assessment on patients who enter mental health
facilities with an established HIV diagnosis or those who are initially
diagnosed after admission.
Assessment should include staging of HIV infection and prescription of
prophylaxis for opportunistic infections, (including tuberculosis in long-term
patients).
Administer and monitor prescribed medications and arrange for appropriate
medical follow-up for patients in psychiatric hospitals.
Start low go slow in advanced and /or symptomatic HIV infection and elderly
patients.
Treat with anti psychotic medications regardless of neuropsychiatric
manifestations of HIV & AIDS
Treat delirium with anti psychotic medications
Note the following precautions:
o Patients with advanced HIV disease are very sensitive to extrapyramidal
side effects and can develop severe parkinsonian symptoms, including the
onset of neuroleptic malignant syndrome occuring within days and
77
tardive dyskinesia occuring within weeks. Standard neuroleptics should
thefore be used in very low doses in these patients.
o Where available, newer atypical anti- psychotic medications are
easier to use.
o Monitor patients continuously as neuropsychiatric symptoms may
improve with treatment and may wax and wane over time monitoring
is recommended.
4.10 Management of central nervous system infections associated with HIV
Condition
Recommended treatment
Comments
Toxoplasmosis Acute Toxoplasma
infection – encephalitis
Co-trimoxazole tablet for each 8kg
bodyweight per day, 12hourly for
4 weeks followed by half the dose
for 8 weeks. Continue with
2tablets per day for life or until the
CD4>200cells/mm3 for 6 months.
OR
Pyrimethamine 100-200 mg
loading dose, then 50-100 mg/day
po + folinic acid 10 mg /day po
(or folic acid)+ sulfadiazine 4-8
gm/day po (or replace sulfadiazine
with clindamycin 300-450 mg po
6 hourly) for at least 6 weeks.
Corticosteroids if significant
oedema/mass effect is present
(Decadron® 4 mg po or IV four
times a day) Consider serial
lumbar puncture to lower raised
intracranial pressure.
Patients who present with focal
neurological signs, or depressed
level of consciousness should have
a CT scan of the head.
When ring enhancing space
occupying lesions are shown,
consider tuberculoma, lymphoma
or toxoplasmosis. Consider
treatment for toxoplasmosis where
there are several lesions. If no
response to treatment consider TB
treatment. If a single lesion is seen
on CT scan, check Toxo serology
and initiate treatment for
toxoplasmosis. If positive
continue, if negative LP where
there is no risk or initiate TB
treatment if patient has systemic
TB symptoms• Anticipated
response is clinical improvement
within one week and improvement
by CT scan within 2 weeks •
Patients who respond to primary
therapy should receive life-long
HAART.
Maintenance therapy (after
successful response to treatment of
acute episode of Toxoplasma
infection)
Co-trimoxazole 2 tablets/day
Pyrimethamine 25-50 mg/d po +
folinic acid 5 mg/day (or Folic
acid) + sulfadiazine 2-4 gm/ day
po (or replace sulfadiazine with
clindamycin 300-450 mg po 6-8
hourly).
Stop when the CD4
count>250cells/mm3 for 6 months
4.10.1 Management of cryptococcal meningitis


Cryptococcal meningitis occurs in individuals who are severely immunocompromised.
Do a lumbar puncture if history of subacute meningitic illness of:
o Headache
78




o unexplained fever
o nausea and vomiting
o neck stiffness
o confusion
o seizures
o abnormal behaviour
o new-onset psychiatric symptoms
o altered level of consciousness
o focal neurological signs
o diplopia
o unexplained blindness
o Coma
Do a CT scan if there are focal neurological signs,
CSF findings consistent with cryptococcal infection include:
o Positive Cryptococcal antigen, Indian ink stain or Cryptococcal
culture.
In rare instances where cryptococcus is isolated from other sites of infection,
therapy should also be initiated due to the high risk of CNS dissemination.
Successfully treated cases of cryptococcal meningitis require secondary
prophylaxis therapy with fluconazole until CD4 > 250 cells / mm3 on
HAART.
Caution should be exercised in prescribing Fluconazole to patients who are taking
Rifampicin; Protease Inhibitors; Warfarin; oral contraceptives; oral Sulphonylureas or
Phenytoin.
Condition
Recommended treatment
Comments
Cryptococcal meningitis 5
Acute treatment (8 weeks):
Induction phase: Amphotericin B
1mg/kg/day IV for up to 14 days
(minimum 1 week)
Consolidation phase: Fluconazole
400 mg/day for 8 weeks.
Secondary prophylaxis:
Fluconazole 200 mg po daily for
life or until the CD4>250cells/ml
for more than 6 months when on
ART
Subsequent episode of CC
Induction phase: Amphotericin B
1mg/kg/doseivi for 2-4 weeks or
until CSF is sterile
Consolidation phase: Fluconazole
800mg po daily for 8 weeks with
or without weekly amphotericin B
1mg/kg
Secondary prophylaxis:
Pain and symptom management:
Reduction of intracranial pressure
alleviates headache and confusion.
Residual pain can be managed
with paracetamol and mild
opiates(WHO level 1 & 2
analgesics). Non-steroidal antiinflammatory drugs should be
avoided in patients on
amphotericin B as they potentiate
nephrotoxicity.
Laboratory diagnosis: .
Definitive diagnosis by culture or
presumptively by tests indicating
the presence of Cryptococcal
species like India ink,
cryptococcal antigen detection test
or mucicarmine-stained
histopathological sections
revealing organisms.
5 Guidelines for the prevention, diagnosis and management of cryptococcal meningitis and disseminated
cryptococcosis in HIV-infected patients. The Southern African Journal of HIV Medicine, Spring 2007; 2535
79
Condition
Neurosyphilis
Recommended treatment
Comments
Fluconazole 400mg podaily for
life (at least 12 months
fluconazole) OR weekly
amphotericin B1mg/kg/dose OR
weekly amphotericin
B1mg/kg/dose plus daily
fluconazole 400mg. Stopped when
CD4>250cells/ml for more than 6
months
Management of raised intracranial
pressure(>20cm CSF): Serial
therapeutic lumbar puncture,
preferably with manometry: •
Measure initial opening pressure
by manometry • Remove ± 2030ml CSF if intracranial pressure
is raised (to decrease opening
pressure by 20-50%) at initial LP.
Ongoing need for pressure relief
should be dictated by recurrence
of symptoms of raised intracranial
pressure. Repeat daily until
opening pressure is normal.
Dosage and administration:
Controlled infusion over 4 hours
of amphotericin B at 1mg/kg in 1
litre of 5% dextrose water should
be given after prehydration with 1
litre normal saline containing
20mmol KCL(1ampoule) run over
2 hours.
AmphotericinB should never be
mixed with normal saline or half
normal saline, nor used to
administer any other drugs.
Infusion should not be faster than
4hrs to avoid cardiac problems.
HAART should be started 2-4
weeks after initiation of antifungal
therapy according national
guidelines
Management of suspected IRIS:
Continue HAART
LP to exclude additional
pathology, check susceptibility
and measure intracranial pressure
CT Head when focal neurological
signs present
Ensure appropriate antifungal
therapy
Treat culture positive cases as per
guidelines, in culture negative
cases continue with the
consolidation phase or secondary
prophylaxis
Oral steroids with prednisone
1mg/kg daily for at least a week if
symptoms fail to respond after
appropriate management of raised
intracranial pressure and
symptomatic treatment or longer if
needed.
Benzathine penicillin ivi 18–24
MU daily, administered as 3–4
MU 4 hourly, for 10–14 days.
Alternative Regimen: Procaine
penicillin imi 2.4 MU daily, for
10–14 days plus Probenecid, oral,
500 mg 4 times a day, for 10–14
Side-effects:
Nephrotoxicity and electrolyte
abnormalities prevented by
adequate prehydration.
Nephrotoxicity occurs in the
second week of amphotericin B.
Baseline and twice weekly
monitoring of creatinine,
magnesium and potassium is
recommended.If creatinine
doubles omit a dose of
amphotericin B or hydrate with
1litre 8hourly. If creatinine
remains elevated stop
amphotericin B and commence
fluconazole. Oral potassium and
magnesium supplements may preempt electrolyte imbalances.
Monitor Hb weekly to check for
anaemia.
Diagnosis is made by CSF
examination showing
mononuclear pleocytosis (10200wcc/ml), mild elevation of
protein and/or positive VDRL.
CSF VDRL is specific but not
sensitive; the CSF FTA-ABS is
80
Condition
Recommended treatment
Comments
days.
These regimens are shorter than
that of the regimen used for late
syphilis in the absence of
neurosyphilis. Therefore, some
experts administer benzathine
penicillin, IM, 2.4 MU after
completion of these neurosyphilis
treatment regimens to provide a
comparable total duration of
therapy. Parenteral penicillin is the
only therapy with documented
efficacy for neurosyphilis. Patients
with neurosyphilis who report
penicillin allergy should always, if
possible, be treated with penicillin,
after desensitization
sensitive but not specific.
Diagnosis is thus difficult due to
the high rate of false negative CSF
VDRLs and the pleocytosis that
can be attributed to HIV in
patients with high CD4 levels.
If neurosyphilis cannot be
excluded the patient should be
treated as such.
4.11 Chronic Diarrhoea
4.11.1 General Principles



Many infective causes of diarrhoea that affect HIV negative individuals occur
commonly in HIV positive patients and should be managed in the same way
as they are treated in HIV negative patients.
Basic food, water and personal hygiene, as well as infection control
procedures should be emphasized.
Ensure hydration with home-made sugar and salt solution: 1 level teaspoon
of salt and 8 level teaspoons of sugar dissolved in 1 litre of boiled then
cooled water.
4.11.2 Management of diarrhoeal disease in HIV
Condition
Symptomatic treatment of
diarrhoea
Recommended treatment
Loperamide, oral, 4 mg
immediately, followed by 2 mg
after each loose stool, up to 16
mg/ day for severe diarrhoea.
or Codeine syrup/tablets 1530mg po 3-5 times a day (as
required).
Comments / Rationale
Diarrhoea is classified as acute
if <2weeks and chronic if > 2
weeks. In acute diarrhoea send
stool for bacterial MCS and in
chronic diarrhoea send for this
as well as coccidian parasites
(microsporidiam,
cryptosporidium and Isospora
belli). If there is a history of
recent antibiotics consider
Clostridium difficile.
Where there is an acute onset
wth fever, blood or mucus in
the stools or LIF tenderness
81
Condition
Recommended treatment
Infective diarrhoea
Usual infective diarrhoea
should be managed in the same
manner in HIV and non-HIV
infected individuals.
Non-invasive bacterial
infections (food poisoning)
Replace electrolytes and fluids
Treat vomiting
symptomatically Antibiotics
are mostly of no value, except
for Enterotoxic E coli and for
Cholera, in which cases, treat
with:
Trimethoprim/sulphamethoxaz
ole (80/400), oral, 2 tablets
twice daily or Doxycycline,
oral, 100 mg twice daily for 5
days.
Invasive bacterial infections
causing diarrhoea
Trimethoprim/sulphamethoxaz
Invasive bacterial infections
causing diarrhoea
Comments / Rationale
send for stool MCS, blood
cultures if febrile and treat with
ciprofloxacin or ceftriaxone if
vomiting.
Oral rehydration should be
prescribed if the diarrhoea is
severe. Diet modification
includes: low fat, no caffeine,
no milk or milk products.
Codeine usage can become
addictive. Stools should be
sent of for culture and
microscopy that includes
investigation for TB
Chronic Diarroea
Rehydrate and correct
electrolytes and send stool for
MCS and coccidian parasites.
Scope if negative. If
inflammatory stool found
(WCC or RBCs on micro) treat
with metronidazole. If does not
settle do sigmoidoscopy and
biopsy. If no inflammatory
stool then gastro-scope for
duodenal biopsy.
Infective diarrhoea may be
suspected, or confirmed on
stool microscopy, culture and
sensitivity Loperamide and
codeine should not be given if
infective diarrhoea is suspected
(eg fever, blood in stool).
Food Poisoning is a Notifiable
Disease. Outbreaks often occur
in institutions.
Attempt to identify the specific
causative agent and antibiotic
sensitivity and give antibiotics
82
Condition
Cryptosporidial diarrhoea
Protease inhibitor associated
diarrhoea
Recommended treatment
ole (80/400), oral, 2 tablets
twice daily for 7 days plus
Metronidazole, oral, 400 mg 8
hourly for 7 days. Fluid and
electrolyte replacement
Comments / Rationale
according to sensitivity.
Widespread resistance to
antibiotics is common.
Appropriate antibiotics should
preferably be selected
according to sensitivity.
Symptomatic treatment with
Non-steroidal antioral rehydration, nutritional
inflammatory agents are
supplements and Loperamide
sometimes useful. HAART is
or Codeine. There are currently the best treatment available
no specific treatments.
Loperamide. Fibre
supplements. Pancreatic
supplements, as indicated.
4.12 Miscellaneous conditions
Condition
Cytomegalovirus Retinitis and
extraocular disease
Mycobacterium avium complex
(MAC) bacteremia
Recommended treatment
Comments / Rationale
Vision threatening lesion:
Intraocular ganciclovir implant
every 6-8 months + valganciclovir
900mg pobid x 14-21 days then
900mg/day.
The goal of therapy is to prevent
further loss of vision and to
control disease using ART.
Discontinue maintenance therapy
when the CD4 count is >100150cells/mm3 for more than 6
months and no active disease.
Gastrointestinal disease is best
treated with valganciclovir 900mg
po bid with food x3 to 4 weeks if
able to swallow otherwise
ganciclovir 5mg/kg ivi bid for 3 to
4 weeks
Clarithroymcin 500 mg po twice a
day plus ethambutol 15 mg/kg/day
+/- rifabutin 300mg/d po.
Start HAART as soon as possible
with in 1-2 weeks of initiation of
MAC therapy. Alternative
regimen: azithromycin 500600mg/day + ethambutol
15mg/kg/day po or Ciprofloxacin
750 mg po twice daily With
HAART, initial results suggest
MAC treatment may be
discontinued when MAC
treatment is >1 yr, CD4 count is
Patients may be asymptomatic or
present with foaters, visual field
defects, scotomata or decreased
acuity. CD4 usually
<50cells/mm3. Fundoscopic exam
shows perivascular yellow-white
retinal infiltrates or lesions with
occasional haemorrhages. Patients
need urgent HAART workup and
commencement
Symptoms are: fever, night
sweats, weight loss, diarrhoea,
abdominal pain, abdominal masses
etc in patients with CD4
counts<50cells/ml.
Diagnosis established by culture
with blood cultures being 90-95%
sensitive using Bactec culture.
. Note interactions of
recommended therapy with
protease inhibitors and NNRTIs.
83
Condition
Anaemia
Septicaemia
Recommended treatment
>100/mm3 for 3-6 months and the
patient is asymptomatic
Treat as per standard clinic
guidelines
Ceftriaxone 1g ivi bd as initial
therapy while causative organism
and sensitivities are awaited
Comments / Rationale
Common and usually related to
HIV and OIs. If the anaemia is out
of keeping with the OI
presentation then investigate other
causes; nutritional, haemolytic,
marrow infiltrates, drugs or
Parvovirus B19 infection
Patients are prone to Gram
positive (staphylococcus) and
Gram negative (salmonella)
septicaemias.
Symptoms: high fever,
hypotension, metabolic acidosis,
source of infection might not be
clear.
Blood cultures are critical
84
SECTION 6: POST-EXPOSURE PROPHYLAXIS (PEP)
1. PROPHYLAXIS AFTER ACCIDENTAL OCCUPATIONAL OR NONOCCUPATIONAL (INCLUDING SEXUAL ABUSE/RAPE) EXPOSURE TO
HIV
1.1 General principles
 Compliance with infection control recommendations in handling blood products,
body fluids or sharps is the mainstay in the prevention of occupational HIV
infection.
 Non-occupational exposure may occur as a result of sexual abuse (rape), with
bite injuries or other violent actions, lay individuals assisting victims of accidents
or violence where there is exposure to blood or body fluids
2. PROPHYLAXIS AFTER OCCUPATIONAL (EXCLUDING RAPE)
2.1 High Risk exposure of infection - Factors that increase the risk of seroconversion include:
Exposure to large inoculum of infected blood indicated by:
 a deep injury
 visible blood on device
 procedures involving needles especially large bore needles/biopsy needles
 Source patient with terminal AIDS or known to have a high viral load, i.e 100
000 copies / ml
In situations where there is a high suspicion that the patient may be in the window
period, consider HIV PCR testing.
2.2 When to commence treatment


Commence treatment as soon as possible within 1 to 2 hours of exposure – the
sooner the better.
Counsel and test the injured person for HIV before initiating HIV prophylaxis.
Dual or interrupted therapy could lead to resistance and endanger future
treatment options.
2.3 Monitoring after occupational exposure



Do laboratory monitoring to exclude acquisition of HIV infection and, for those
given PEP, to monitor toxicity.
Test for HIV infection using an HIV antibody test at time of exposure using
ELISA, and again at 6 weeks, 3 months and 6 months.
Counsel on practicing safe sex until HIV test is negative 6 months following
exposure
85

Do a full blood count before initiating patients on AZT and after 2 and 4 weeks
on antiretroviral therapy. Relative contra-indications to the use of AZT include
significant renal or liver impairment and severe anaemia (Hb < 6, 5 g/dl).
2.4 Recommended PEP drug regimen
a) For standard risk, basic two drug regimen
AZT, oral, 300mg 12 hourly for 4 weeks
AND
3TC, oral, 150 mg 12 hourly for 4 weeks
b) For high risk, expanded three drug regimen
ADD
Lopinavir / ritonavir 133 / 33, oral, 3 capsules 12 hourly
3. PROPHYLAXIS AFTER SEXUAL ASSAULT
3.1 High risk profile rape includes:
o where there have been multiple perpetrators
o anal penetration
o obvious trauma to the genital areas
o Female menstruating at time of rape, or with genital ulcerations/sores
o Known HIV positivity of one of the perpetrators
3.2 Follow guidelines on STI/Pregnancy prophylaxis
 Counsell all women and men, aged 12 years and older presenting to a health
facility after being raped, about the potential risks of HIV transmission postrape.
 Offer PEP to prevent HIV transmission to all women and men, aged 12 years
and older, presenting to a health facility within 72 hours of being raped.
 Manage younger managed at specialized sites where there is the expertise in
dealing with traumatized children and the prescription of HAART.
3.3 The following points should be covered in the counselling:
 Counsel all patients presenting after 72 hours about the possible risk of
infection and the possibility of them transmitting infection during seroconversion.
 Provide appropriate post trauma counselling with follow up to all patients.
3.4 Where the risk of HIV transmission is not known, but exists.
 Know the victim’s HIV status prior to using any HAART.
 Delay but not for longer than 72 hours post-rape as it is the patient’s choice
to have immediate HIV testing if she/he prefers.
 Provide a 3-day starter pack for those who prefer not to test immediately, or
those that are not ready to receive results immediately.
86






Counsell patients who request prophylaxis after 72 hours about lack of
scientific evidence that the use of PEP delayed this long after the rape will
have any impact on preventing HIV transmission
Give patients a week supply of PEP.
Give a date to return within a week for:
o reassessment
o ongoing counselling
o Review of test results (except the rapid HIV or to obtain the
confirmatory ELISA, where positive).
Give the remainder of the drugs at this visit (i.e. a 3-week supply).
Give a month’s treatment supply with an appointment date for those patients
who cannot return for their one-week assessment due to logistical or
economic reasons.
Do not offer prophylaxis to patients who are either known to be HIV positive,
or who test HIV positive. Refer to an appropriate health care clinic for longterm management of their HIV infection
3.5 Recommended PEP drug regimen
For standard risk, basic two drug regimen
AZT, oral, 300mg 12 hourly for 4 weeks
AND
3TC, oral, 150 mg 12 hourly for 4 weeks
For high risk, expanded three drug regimen
ADD
Lopinavir / ritonavir 133 / 33, oral, 3 capsules 12 hourly
87
Figure 1: PEP after sexual assault
Patient allegedly
sexually assaulted
Documentation for all
patients to open folder
Medical examination
for STI and pregnancy;
Counselling
Assault occurred less than
72 hours ago
Yes
No
Counselling 3-days
PEP starter pack
Consent HIV test
HIV
negative
HIV
positive
Baseline HIV,
FBC, LFTs
HIV positive
Refuse test
HIV negative
NO PEP
PEP
Routine
follow-up
Patient referred for further
HIV management
Follow-up blood tests
6 & 12 weeks and 6 months
88
APPENDIX 1: WHO clinical staging of HIV & AIDS for
adults with confirmed HIV infection (2006)
Clinical Stage 1
1. Asymptomatic
2. Persistent generalized lymphadenopathy (PGL)
Clinical Stage 2
3. Unexplained moderate weight loss <10% of presumed or measured body weight
4. Recurrent respiratory tract infections (e.g. bacterial sinusitis) (URTI) and/or
performance Scale 2: symptomatic, normal activity.
5. Herpes zoster within the last five years
6. Angular cheilitis
7. Recurrent oral ulceration
8. Papular puritic eruptions
9. Seborrhoeic dermatitis
10. Fungal nail infections
Clinical Stage 3
11. Unexplained severe weight loss >10% of presumed or measured body weight
12. Unexplained Chronic diarrhoea >one month
13. Unexplained presistent fever (above 37.5ºC intermittent or constant) >one month
14. Persistent oral candidiasis
16. Oral hairy leukoplakia
17. Pulmonary TB
18. Severe bacterial infections (pneumonia, empyema, pyomyositis, bone or joint
infections, meningitis or bacteraemia)
19. Acute necrotizing ulcerative stomatitis, giingivitis or periodontitis
20. Unexplained anemia (<8g/dl), Neutropaenia (<0.5 x 109 per litre) and/or chronic
thrombocytopaenia (<50 x 109 per litre)
Clinical Stage 4
21. HIV wasting syndrome
22. Pneumocystis pneumonia
23. Recurrent severe bacterial pneumonia
24. Chronic herpes simplex infection (orolabial, genital or anorectal of >1 months
duration or visceral at any site)
25. Oesophagael candidiasis (or candidiasis of trachea, bronchi or lungs)
26. Extrapulmonary tuberculosis
27. Kaposis sarcoma\ Cytomegalovirus infection other than liver, spleen or lymph node
(CMV)
28. CNS toxoplasmosis (Toxo)
29. HIV encephalopathy (ADC)
30. Cryptococcosis – non pulmonary
31. Disseminated mycosis (i.e. histoplasmosis, coccidiomycosis)
32. Progressive multifocal leucoencephalopathy (PML)
33. Cryptosporidiosis plus diarrhoea >one month
89
34. Chronic Isosporiasis plus diarrhoea
35. Herpes simplex infection; visceral or >one month mucocutaneous (HSV)
36. Atypical mycobacteriosis disseminated (MOTT)
37. Atypical disseminated leishmeniasis
38. Non-typhoidal Salmonella septicaemia
39. Extra-pulmonary tuberculosis (ETB)
40. Lymphoma
41. Kaposi’s sarcoma (KS)
42. Invasive cervical carcinoma and/or performance
43. Symptomatic HIV-associated nephropathy or symptomatic HIV-associated
cardiomyopathy
90
APPENDIX 2 : ADULT PATIENT ADHERENCE RECORD
& MONITORING FORM [PARMF]
Please complete all sections of the PARMF unless otherwise indicated
1. Patient Details:
Surname:
Folder no:
First Name:
Date: dd / mm / yy
D.O.B.:
2. Date of Treatment initiated: dd / mm / yy
3. Duration of treatment: Months □Years □
4. Pill Identification Test (PIT)
Ask the patient to inspect the container and its content. The patient should then tell
you the name of the medication, number of pills to take per dose, the times when
the medication are taken and whether there are any additional instructions
Medication Knows
the name
Y/ N
Knows the
no of pills
per dose
Y/N
Time the medication is taken
Morning Evening Judged
hour
hour
correct
Y/N
Knows any
additional
information
5. Medication Pick-Up Dates:
Mon
th
1
2
3
4
5
6
To Come
Again
(Appt. Date)
Pick Up
Date
Variance Mon
(days)
th
To Come
Pick Up
Again
Date
(Appt. Date)
Variance
(days)
7
8
9
10
11
12
91
6. Pill Count:
Did the client return the medication containers? Yes / No
If yes, check that the patient only used medication from this container since the
date of the last visit. If leftover medication has been used or an emergency
prescription obtained then the calculation will be invalid.
Count the remaining number of pills on the collection date
Calculate the Adherence as follows:
% Adherence =
Dispensed − Returned / Expected to be taken × 100
Dispensed =
pills remaining at last visit + pills issued at last visit
Returned =
pills remaining now
Expected to be taken =
number of pills taken per day x number of days
passed since last visit
Then collate Adherence Monitoring Record (%) using the table provided below:
6.1 Adherence Monitoring Record (%):
Medications M1 M2 M3 M4 M5 M6 M7 M8 M9 M10 M11 M12
Date
7. Visual Analogue Scale (VAS): Insert a √ in the relevant box and then insert %
Adherence (see Table below)
 Ask the patient to think back over the past 4 days and identify the times when he
/ she either missed a dose or took it at the wrong time.
 Show the patient an unmarked copy of the visual analogue scale.
 While placing your finger on the appropriate place, tell the patient that if he / she
had taken all medication doses to point to 10.
 If the patient missed all the doses he / she would point to 0.
 In the meantime you move your finger to 0.
 Now give the patient an opportunity to point out their level of adherence.
 The health care worker then marks the visual analogue scale.
 If the scale is marked at 4, then the percentage adherence would be 40%.
92
Month
Date
0
1
2
3
4
5
6
7
8
9
10 %Adherence
S
c
o
r
e
M1
M2
M3
M4
M5
M6
M7
M8
M9
M10
M11
M12
8. Self – Reporting: (Insert a √ in the relevant box to indicate the patient’s response)
Month
1
2
3
4
5
6
7
8
9
10
Date
Question Y N Y N Y N Y N Y N Y N Y N Y N Y N Y N
Do you
sometimes
find it
difficult to
remember
to take
your
medicine?
93
11
12
Y N Y N
When you
feel better,
do you
sometimes
stop
taking
your
medicine?
Thinking
back over
the past 4
days, have
you
missed
any of
your
doses?
Sometime
s if you
feel worse
when you
take the
medicine,
do you
stop
taking it?
9. Adherence Assessment (Mark the response provided with a √)
Pick Up Date
Pill Count
VAS
Self-Reporting
OVERALL
ADHERENCE
0 – 2 days
3 – 5 days
> 5 days
> 95%
75 – 94 %
< 75%
> 95%
75 – 94%
< 75%
Answered “No” to all Answered “Yes” to 1 Answered “Yes” to
questions
question
2 or more questions
HIGH (H)
MODERATE (M)
LOW (L)
10. Fill in table provided below to show adherence per tool used per month
Month
1
2
3
4
5
6
7
8
9
10
11
12
Date
Pick Up Date
Pill Count
VAS
SelfReporting
94
OVERALL
ADHEREN
CE
11. Recommendations
MODERATE ADHERENCE
Low Intervention: Adherence Counselling
LOW ADHERENCE
High Intervention: Intense Retraining and
Counselling
Revision of Dosage Regimens / Training Review with Patient Advocate
Revision
Re-assurance
Home Visit
95
APPENDIX 3: TB PROPHYLAXIS
Guidelines for tuberculosis (TB) preventive therapy among HIV
positive patients
Background
 The spread of the HIV epidemic throughout sub-Saharan Africa in the past
decades has been accompanied by up to a fourfold increase in the number of TB
cases registered by the national TB programmes.
 Strategies to control TB must now include interventions to reduce HIV infection.

On the other hand, it is estimated that around 50% of new adult cases of TB in
South Africa are co-infected with HIV.

TB is the commonest cause of morbidity and mortality among HIV-infected
population in South Africa.

There is scientific evidence that shows that TB does accelerate HIV-disease
progression. Therefore, preventive TB therapy should be offered in the package
of care for people living with HIV.

TB preventive therapy is the use of one or more anti-tuberculosis drugs given to
individuals with latent infection with M. tuberculosis in order to prevent the
progression to active TB disease.

There is scientific evidence that shows that maximum benefits from TB
preventive therapy are achieved in HIV positive patients with evidence of TB
infection.

Providing IPT to these patients reduces the risk of developing TB by 60%, and
their survival is also prolonged.
TB preventive therapy and health services

Provide TB preventive therapy as part of the package of care for people living
with HIV after:
o voluntary counselling and testing for HIV
o effective screening for active TB
96
APPENDIX 4: EXCLUSION OF ACTIVE TB




Exclude active TB in every patient prior to starting preventive therapy. This is
critical in order to avoid giving one drug to patients with TB disease who require
the full regimen.
Ask patients about signs and symptoms of TB:
o Cough >2 weeks
o Fever >2 weeks
o Night sweats
o Other symptoms, like pleuritic chest pains, haemoptysis should also
prompt investigations for TB
o Weight loss of >1.5 kg in the past 4 weeks
Investigate all patients with 1 or more signs and symptoms for active TB. These
patients are not immediately eligible for TB preventive therapy until active TB
has been excluded.
Reassess patients with symptoms / signs after 3 months for TB preventive if they
are not confirmed with TB (smear and culture are both negative), and they
recover from their illness
NOTE: Symptoms are adequate to exclude active TB in advanced disease, but with
CD4 > 250 symptoms are insensitive. In these patients it is suggested that sputum
specimens must be collected for the following investigations:
 sputum samples for microscopy
 1 sputum for culture
 A chest x-ray must not be a barrier for people to access IPT. Emphasis is on
sputum samples for microscopy and culture and, where appropriate, on
identification of extra pulmonary TB.
 Do a chest ONLY in those who are TB suspects with negative sputum smears.
97
APPENDIX 5
1. ELIGIBILITY FOR TB PREVENTIVE THERAPY
All HIV-positive people, with no signs and symptoms suggestive of active TB, with
positive tuberculin skin test, are eligible for TB preventive therapy.

Give particular attention to:
o Miners
o Prisoners
o TB contacts
o Health care workers
1.1 Who is not eligible for TB preventive therapy?




Patients with active liver disease or active alcohol abuse should not be offered
TB preventive therapy. This is because of potential hepatotoxicity of the drug
used for preventive therapy.
Patients with history of TB treatment:Any patient, who had active TB in the past
2 years, should not be offered TB preventive therapy.
Patients on HAART should not be offered TB preventive therapy, as there is
currently no scientific evidence of added benefit.
Patients who receive TB preventive therapy, and who require to start HAART,
can complete their TB preventive therapy even if the HAART is started. This is
because there is no interaction between isoniazid and the current HAART
regimen used.
2. TUBERCULIN SKIN TEST








The tuberculin skin test measures the body’s immune response to an injection of
tuberculin purified protein derivative (PPD).
The Mantoux test is the recommended technique that injects a known amount of
PPD between the layers of the skin (intradermally).
The injection must go into the skin and not under the skin.
The reaction is measured at the site of injection 48-72 hours later.
Measure the induration (not the eventual erythema) accurately
To help measure accurately, mark the edges of the induration at the widest point
with a pen (two point pen method). Then measure the exact distance between the
two points.
Measure the diameter of the reaction at the widest points of the raised, thickened
area.
Record the result in millimetres.
98
2.1 Positive tuberculin skin test results:
Tuberculin test
Mantoux
Previous BCG
NO previous BCG HIV positive
Greater or equal to Greater or equal to >4 mm
15mm
10mm
2.2 What does a positive tuberculin skin test mean?



A positive test indicates infection with TB, but not necessarily TB disease.
A positive reaction occurs after BCG immunisation and remains positive for
several years thereafter.
This reaction is usually weaker than the reaction to natural infection with M.
tuberculosis.
2.3 Conditions that may reduce or suppress the tuberculin skin test include:
o HIV infection
o Malnutrition
o Severe viral infections (e.g. measles, chicken pox)
o Cancer
o Immuno-suppressive drugs (e.g. steroids)
o Severe disseminated TB
3. RECOMMENDED REGIMEN
The standard regimen for TB preventive therapy is:
Isoniazid (INH) daily.
The dose is: 5 mg/kg/day (maximum 300 mg per day).
The recommended duration is: 6 months.


Give additional Vitamin B6 (Pyridoxine) in sufficient dosage to prevent the
eventual occurrence of peripheral neuropathy.
IPT protective effect is expected to last for 18 months.
99
Figure 2: Screening for tuberculosis preventive therapy flowchart among HIV
positive patients.
HIV-positive patient
Complete patient chart
Clinical status and screening for
suitability for PT
Not eligible for IPT;
provide co-trimoxazole
prophylaxis
Previous TB treatment
past 2 years
TB symptoms or signs
NO
YES
PPD test
Sputum smear & culture
PPD positive
Smear negative
Smear
positive or
culture
Antibiotics
Visit 2 /
Follow up
Offer IPT and
counselling
about IPT
Commence
IPT
PPD negative
No IPT
Patient
refuses IPT
Good response
to antibiotics
Reassess and
reconsider screening
for IPT after 3 months
Poor response
to antibiotics
Refer for further
investigations for
PTB, EPTB or other
possible conditions
TB treatment;
co-trimoxazole
prophylaxis
100





Read result after three days (48-72 hrs)
Offer TB preventive therapy if the skin test is positive
Offer on-going counseling about :
o HIV
o Symptoms of side-effects of isoniazid (minor: peripheral neuropathy) (
major: jaundice, vomiting and confusion, due to hepatitis)
o Adherence counseling
o Early detection of active TB
o seeking care immediately if they develop an illness
Give one month at a time supply to patients starting TB preventive therapy.
Give a subsequent appointment to review the condition if Tuberculin test
negative
Patients should come for review if any symptoms of active TB occur.
4. CONTRAINDICATIONS TO IPT
 Stop IPT and start the full TB treatment regimen if the patient develops active
TB
 Stop IPT immediately, and refer signs and symptoms suggestive of hepatitis
5. WHEN THE PATIENT INTERRUPTS THERAPY
 Enquire about the possible reasons for interrupting.
 Counsel on the importance of adherence appropriately.
 Restart the therapy after assessing the reasons for bad adherence.
 Ensure that the 6 months therapy is taken within a 9-month period.
 Stop IPT if the patient interrupts for the second time
These TB preventive guidelines may be reviewed upon evidence of new
developments.
List of contributors (Please acknowledge sources of all information especially around the
managemnt of side effects and the management of OIs because that is clear cut-and –
paste)!
o Table of contents
o Definiftions
o Abbreviations
101