Download Human Immunodeficiency Virus (HIV) and Acquired

Based on Scaling up HIV Treatment in Resource Limited Settings: WHO Guidelines, 2006
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1. Natural History of HIV Infection
1.1 HIV Basics
1.2 Guidelines and Principles of HIV Testing
1.3 Laboratory tests Specific to HIV Infection
1.3.1
HIV Serology (antibody tests): ELISA AND Western Blot
1.3.2
CD4 Cell Count
1.3.3
Total Lymphocyte Count (TLC)
1.4 Clinical Presentation and Natural History of HIV Infection:
1.4.1
Acute Primary HIV infection
1.4.2
Opportunistic Infections
1.4.3
WHO Clinical Staging of HIV Infection
Annexure 1.1: WHO clinical staging of HIV disease in adults and adolescents
Annexure 1.2: Criteria for HIV-related clinical events in adults and adolescents
1. Natural History of HIV Infection – Clinician Sept06 V
Source: Clinician Software 2006
Based on Scaling up HIV Treatment in Resource Limited Settings: WHO Guidelines, 2006
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1. Natural History of HIV Infection
1.1 HIV Basics
HIV is a retrovirus and is a RNA virus. It affects only human being and spreads when
there is exchange of following body fluids
- Blood or blood products, Intravenous drug use
- Vaginal, anal secretions and semen
- Placental fluid (mother to child transmission)
- CSF Fluid
- Breast mild
Route of Transmission:
1. Sexual
2. Transfusion of HIV infected Blood & blood products
3. Mother to Child (During pregnancy, labor and in postnatal period through breast
milk)
4. Intravenous Drug Use
5. Unidentified
HIV Types and Subtypes: Phylogeny of HIV Virus: HIV -1 and HIV-2 are two types.
HIV-1 is the most common cause of infections in the world. HIV-1 consists of two
subtypes:
- Subtype O
- Subtype M: Subtype M has following subtypes: A,B,C,D,E,F,G,H,I J and K
The geographic distribution across the globe varies.
HIV-2 is primarily seen in West Africa. Compared to HIV-1;
- HIV-2 is less transmissible (5- to 8-fold less efficient than HIV-1)
- HIV-2 is rarely the cause of vertical transmission
- Associated with lower viral load
- Causes slower rate of both CD4 cell decline and clinical progression.
- Usually co-infected with HIV-1 also.
- Not susceptible to NNRTI class and possibly PI
- No test available to perform HIV-2 viral load
Demographics: It affects people of all age groups and depends on the mode of spread.
1. In general all those who are sexually active and have unprotected sex (with out a
condom) are at risk of HIV infection.
2. Men and women are equally affected
3. Children born to HIV infected mothers.
4. Recipients of HIV infected blood
5. Occupational exposure at health care facility through blood stained (from HIV
infected person) needles, syringes, knives, etc.
6. Intra Venous drug users.
1. Natural History of HIV Infection – Clinician Sept06 V
Source: Clinician Software 2006
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1.2 Guidelines and Principles on HIV Testing
Guidelines on HIV Testing: HIV testing carried out on a voluntary basis with
appropriate pre-test and post-test counselling
The objectives of testing are to:



Testing for HIV is more than a mere biological test for it involves ethical, human
and legal dimensions.
There is no public health rationale for mandatory testing of a person for
HIV/AIDS.
HIV testing carried out on a voluntary basis with appropriate pre-test and post-test
counselling is considered to be a better strategy and is in line with the national
policy on HIV testing and also the WHO guidelines.
General Principles of HIV Testing: HIV Testing should be done with ‘explicit’ consent
of the patients Mandatory testing has proved to be counter productive in the control of
HIV epidemic.
In a population where the prevalence of infection is 1%, the chance that a person detected
positive is actually positive (positive predictive value) is only 50% after one ELISA test
and 99% turly after two tests. This means one result will be falsely positive in every 100
tests, even by two tests if we use a western blot as supplemental test instead of 2nd
ELISA, the chance of detecting truly positive increased to 99.998% which means there
will be one false positive out of 10,000 declared positive.
Presently three types of tests are available on similar principle to ELISA which has been
broadly categorized, as one which can be completed within half an hour.
The result of the test must be kept confidential and even health care workers who are not
directly involved in care of the patient should not be told about the result.
No mandatory HIV testing should be imposed as a precondition for employment or for
providing health care facilities during employment.
1. Natural History of HIV Infection – Clinician Sept06 V
Source: Clinician Software 2006
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1.3 Laboratory tests Specific to HIV Infection
1.3.1
HIV Serology (antibody tests): ELISA AND Western Blot
Standard test consists of a screening Enzyme Linked Immuno Assay (ELISA) followed
by a confirmatory Western Blot.
Standard ELISA has sensitivity and specificity rates of > 98%. Positive tests should be
confirmed by repeat tests. If ELISA is repeatedly (two or more times) positive then a WB
is considered for confirmation.
False Negative Results:
2 Usually due to testing in the “window period”. Ranges from 0.3% in a high
prevalence area to <0.001% in low prevalence areas. Causes:
- Window Period: Time delay from infection to positive ELISA. This period last 3-4
weeks from the time of acquiring HIV infection. Eventually all seroconvert (ELISA test
becomes positive) in six months. If a HIV test is negative in a person suspected to be in
the “window period” the test should be repeated every 2 months until 6 months from day
of (suspected or confirmed) exposure to HIV source.
- If HIV test kits do not test for HIV-2 antibody then HIV-2 infection can be missed
In Adults, and children > 18 months:
Diagnosis of HIV infection is made with:
positive HIV antibody testing (rapid or laboratory based EIA). This is
usually confirmed by a second HIV antibody test (rapid or laboratory
based EIA) relying on different antigens or of different operating
characteristics.
Diagnosis of HIV infection is made with:
positive virological test for HIV or its components (HIV-RNA or HIVDNA or Ultrasensitive HIV p 24 antigen) confirmed by a second
virological test obtained from a separate determination.
1.3.2
CD4 Cell Count
This is a standard test to assess prognosis for progression to AIDS or death and helps in
formulating a differential diagnosis in a symptomatic patients. CD-4 cell count helps in
taking decisions to start HIV treatment; both ART and prophylactic medications for
opportunistic infections. CD4 test is not to be used to make a diagnosis of HIV infection.
The normal value ranges from 500-1500 cells/mm3.
CD8 cells have not been found to predict outcome of HIV infection and are not used in
clinical practice.
1. Natural History of HIV Infection – Clinician Sept06 V
Source: Clinician Software 2006
Based on Scaling up HIV Treatment in Resource Limited Settings: WHO Guidelines, 2006
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Frequency of Testing: The CD4 count should be repeated every 3-6 months in untreated
patients and probably more often in those on treatment. The frequency is many times
dictated by availability of testing facility. (refer to table x )
The test should be repeated if results are inconsistent with prior trends or clinical picture.
In the absence of ART, average rate of CD4 decline is 4% per year (for each log10 HIV
RNA c/mL).
In clinical practice it is important to be aware of variability in CD4 test results. If the test
shows a value of 200, the range of CD4 cell count in the body ranges from 118-337
cells/mm3.
The trend (increase or decrease) in CD4 cell count change should be given emphasis
rather than on one single CD4 test count. If the CD4 cell count is inconsistent with prior
trends then it should be repeated.
Factors that Influence CD4 Cell Counts:
1. Analytical variation: CD4 Cell count is product of three variables:
 Total WBC Count
 Percentage of Lymphocytes
 Percent of CD4 count
2. Seasonal variation
3. Diurnal Variation : Lowest levels at 12.30 PM and Peak values at 8.30 AM.
4. Concurrent illnesses (infections) : Modest decreases noted with some acute
infection and with major surgery.
5. Corticosteroids: have profound effect, with decreases from 300-900 cells/mm3
with acute administration of steroids. Chronic administration has less profound
effect.
6. Splenectomy: CD4 percentage should be used for clinical monitoring in such
instances
CD4 Count Percentage: CD4 count % as compared to absolute CD4 count is used for
initiating and monitoring the treatment in children.
Table 1.3.1.1: Approximate CD4/CD4% Equivalents
CD4 Cell Count
% CD 4
> 500 / MM3
200-500 / MM3
< 200 / MM3
> 29%
14% - 28%
< 14%
1. Natural History of HIV Infection – Clinician Sept06 V
Source: Clinician Software 2006
Based on Scaling up HIV Treatment in Resource Limited Settings: WHO Guidelines, 2006
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CD4 Cell Count Response to ART: After initiating treatment if ART is effective in
suppressing the HIV virus effectively the increase in CD4 count is typically >= 50
cells/mm3 after 4-8 weeks.
Thereafter an additional increase of 50-100 cell/mm3/year thereafter until it reaches the
normal range.
When Therapy is stopped: The CD4 counts declines rapidly, up to 100-150 cells/mm3 in
3 to 4 months.
1.3.3
Total Lymphocyte Count (TLC)
The TLC is used as a surrogate for CD4 count where CD4 count is not available.
TLC of < 1200/mm3  CD4 cell < 200 cells/mm3 (in combination with clinical picture)
is an indication to start HIV treatment with ART.
1. Natural History of HIV Infection – Clinician Sept06 V
Source: Clinician Software 2006
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1.4 Clinical Presentation and Natural History of HIV Infection
1.4.1. Acute Primary HIV infection
-
Symptoms are vague and occur 2-3 weeks after HIV infection.
Commonly presents as fever, lymphadenopathy, pharyngitis, erythematous
maculopapular rash on ace and trunk and myalgia.
Other presentations: Diarrhea, headache, Hepatosplenomegaly, weight loss, thrush and
neurolgoic symptoms (aseptic meningitis, peripheral neuritis, etc).
This phased (refer to graph above) is characterized by a very high viral load in order of 1
million copies/mL and the chances of transmitting infection to others is high in this
period.
Table 1.4.1: The natural history of untreated HIV infection is divided into the
following stages:
Stages
interval
From
Infection
 Viral Transmission  Acute retroviral Syndrome 2-3 weeks
2-3 w
 Recovery + Seroconversion (HIV+ antibody test)
2-4 weeks
4-6 w
 Asymptomatic Chronic HIV infection
2-4 weeks
6-8 w
 Symptomatic HIV infection/AIDS
~ 8 Years
~ 8 Years
 Death (progression marked by OI’s)
~ 1-3 years
~ 1-3 years
Graph 1.4.1: Clinical Presentation and Natural History of HIV Infection:
Natural History of HIV Infection
CD4 Count, Viral Load and Clinical Course of Untreated HIV Infection in Adults
Primary
Infection
Seroconversion
10,000,000
Intermediate Stage
AIDS
Plasma HIV RNA
1,000
100,000
10,000
Viral Load
1,000
100
500
CD4 Cells
CD4 Cell Count
1,000,000
AIDS
200
10
1
4-8 Weeks
5-10 Years to AIDS
Natural History of HIV Infection
1. Natural History of HIV Infection – Clinician Sept06 V
Survival with
AIDS 1 year
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Source: Clinician Software 2006
Based on Scaling up HIV Treatment in Resource Limited Settings: WHO Guidelines, 2006
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1.4.2. Opportunistic Infections
HIV infection is characterized by opportunistic infections. The CD4 threshold when these
infections occur varies for different pathogens. It is important to be familiar with these
threshold so that timely prophylaxix can be offered to prevent these opportuntsitc
infections. For example all those with CD-4 </= 200 should be on Bactrim ds to prevent
Pnumocysitic Jiroveci pneumonia
Table 1.4.2.1: Correlation of Complications With CD4 Cell Counts.
CD4 Count
Cells/mm3
Infectious Complications
Noninfectious Complications
 Acute Retroviral Syndrome
 Candida Vaginitis
 Persistent Generalized
Lympadenopathy (PGL)
 Guillane-Barre Syndrome
 Myopathy
 Aseptic Meningitis
 Cervical intraepithelial
neoplasia
 Cervical cancer
 B-cell lymphoma
 Anemia
 Mononeural Mulitplex
 Idiopathic thrombocytopenic
purpura
 Hodgkins lymphoma
 Lymphocytic interstitial
pneumonitis
 Wasting
 Peripheral neuropathy
 HIV associated dementia
 Cardiomyopathy
 Vacoular myelopathy
 Progressive polyradiculopathy
 Non-Hodgkins’s lymphoma

> 500
200-500
<200
<100
<50
 Penumococcal and other
bacterial pneumonia
 Pulmonary TB
 Herpes Zoster
 Oropharyngeal Candidiasis
(Thrush)
 Cryptosporidiasis, self limited
 Kaposi’s sarcoma
 Oral hairy leukoplakia
 Pneumocystis carinii
pneumonia
 Dissiminated histoplamosis and
cocciodiodomycosis
 Miliary/extrapulmonary TB
 Progressive multivocal
leukoencephalopaty (PML)
 Disseminated herpes simplex
 Toxoplasmosis
 Cryptococcosis
 Crytosporidiosis, chronic
 Microsporidiosis
 Candidal esophagitis
 Dissimnated cytomegalovirus
(CMV)
 Disseminated Mycobacterium
1. Natural History of HIV Infection – Clinician Sept06 V
 Central nervous system (CNS)
lymphoma
Source: Clinician Software 2006
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avium complex
* most complication occur with increasing frequency at lower CD4 cell counts
+ Some conditions listed as “noninfectious” are probably associated with transmissible
microbes. Examples include lymphoma (Epstein-Barr Virus [EBV]) and cervical cancer (human
papilloma virus).
Source: Medical Management of HIV Infection. John G. Bartlett. 2004
1. Natural History of HIV Infection – Clinician Sept06 V
Source: Clinician Software 2006
Based on Scaling up HIV Treatment in Resource Limited Settings: WHO Guidelines, 2006
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1.4.3. WHO Clinical Staging of HIV Infection
Clinical staging of HIV infection is useful guide in the management of both preventing
opportunistic infections and in the management of antiretroviral therapy. Diagnosis of
AIDS: is based on lab and clinical presentation
A) CD4 Cell Count < 200 cell/mm3 and presence of
B) AIDS indicator conditions:
1. HIV wasting syndrome, as defined by CDC a
2. Pneumocystis carinii pneumonia
3. Toxoplasmosis of the brain
4. Cryptosporidiosis with diarrhea, 1 month
5. Cryptococcosis, extra-pulmonary
6. Cytomegalovirus (CMV) disease of an organ other than liver, spleen or lymph
nodes
7. Herpes simplex virus (HSV) infection, mucocutaneous 1 month, or visceral any
duration
8. Progressive multi focal leukoencephalopathy (PML) and CNS lymphoma
9. Any disseminated endemic mycosis (i.e. histoplasmosis, coccidioidomycosis)
10. Candidiasis of the esophagus, trachea, bronchi or lungs
11. Atypical mycobacteriosis, disseminated
12. Non-typhoid Salmonella septicemia
13. Extra-pulmonary tuberculosis
14. Non-Hodgkins Lymphoma
15. Kaposi’s sarcoma (KS)
16. HIV encephalopathy, as defined by CDC b
17. Disseminated Mycobacterium avium complex
Differential Diagnosis:
HIV infection is a great mimicker. Clinical presentation and hence the differential
diagnosis of HIV infection depends on clinical stage of HIV infection. Generally, except
in the acute primary infection stage clinical manifestations of HIV are due to
Opportunistic Infections.
For the purpose of making decision on when to treat, HIV infection is staged as WHO
guidelines Annexure 1.1. The Criteria for HIV-related clinical events in adults and
adolescents is listed in Annexure 1.2
CLASSIFICATION OF HIVASSOCIATED CLINICAL DISEASE
WHO CLINICAL STAGE
Asymptomatic
Mild
Advanced
Severe
1
2
3
4
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Annexure 1.1: WHO clinical staging of HIV disease in adults and adolescents
(Note: both definitive and presumptive diagnoses are acceptable)
Clinical Stage I: Asymptomatic
1. Asymptomatic
2. Persistent generalized lymphadenopathy (PGL)
3. Performance scale 1: Asymptomatic, normal activity
Clinical Stage II: Mild
1. Weight loss, 10% of body weight
2. Minor mucocutaneous manifestations (seborrheic dermatitis, prurigo, fungal nail
infections, recurrent oral ulcerations, angular cheilitis)
3. Herpes Zoster, within the last 5 years
4. Recurrent upper respiratory tract infections (i.e., bacterial sinusitis)
5. And/or Performance scale 2: symptomatic, normal activity
Clinical Stage III: Advanced
1. Weight loss, 10% of body weight
2. Unexplained chronic diarrhea, 1 month
3. Unexplained prolonged fever (intermittent or constant), 1 month
4. Oral candidiasis (thrush)
5. Oral hairy leukoplakia.
6. Pulmonary tuberculosis, within the past year
7. Severe bacterial infections (i.e., pneumonia, pyomyositis)
and/or performance scale 3: bed-ridden, 50% of the day during the last month
Clinical Stage IV: Severe
1. HIV wasting syndrome, as defined by CDC (1)
2. Pneumocystis carinii pneumonia
3. Toxoplasmosis of the brain
4. Cryptosporidiosis with diarrhea, 1 month
5. Cryptococcosis, extra-pulmonary
6. Cytomegalovirus (CMV) disease of an organ other than liver, spleen or lymph
nodes
7. Herpes simplex virus (HSV) infection, mucocutaneous 1 month, or visceral any
duration
8. Progressive multi focal leukoencephalopathy (PML)
9. Any disseminated endemic mycosis (i.e. histoplasmosis, coccidioidomycosis)
10. Candidiasis of the esophagus, trachea, bronchi or lungs
11. Atypical mycobacteriosis, disseminated
12. Non-typhoid Salmonella septicemia
13. Extra-pulmonary tuberculosis
14. Lymphoma
15. Kaposi’s sarcoma (KS)
16. HIV encephalopathy, as defined by CDC (2)
17. And/or Performance scale 4: bed-ridden, 50% of the day during the last month
1. Natural History of HIV Infection – Clinician Sept06 V
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1. HIV wasting syndrome: Weight loss of 10% of body weight, plus either unexplained
chronic diarrhea (1mth), or chronic weakness and unexplained prolonged fever (1mth).
2. HIV encephalopathy: Clinical findings of disabling cognitive and/or motor dysfunction
interfering with activities of daily living, progressing over weeks to months, in the
absence of a concurrent illness or condition other than HIV infection that could explain
the findings.
1. Natural History of HIV Infection – Clinician Sept06 V
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Annexure 1.2: Criteria for HIV-related clinical events in adults and adolescents
CLINICAL STAGE 1
CLINICAL EVENT
CLINICAL DIANGOSIS
DEFINITE DIAGNOSIS
Asymptomatic
No HIV-related symptoms
reported and no signs on
examination
Painless enlarged lymph
nodes >1 cm, in two or
more noncontiguous sites
(excluding inguinal), in
absence of known cause
and persisting for three
months or longer
Not applicable
CLINICAL EVENT
CLINICAL DIANGOSIS
DEFINITE DIAGNOSIS
Moderate unexplained
weight loss (under 10% of
body weight)
Reported unexplained
weight loss. In pregnancy,
failure to gain weight
Documented weight loss
(under 10% of body weight)
Recurrent bacterial upper
respiratory tract
Infections (current event
plus one or more in last
six months)
Symptoms complex, e.g.
unilateral face pain with
nasal discharge (sinusitis),
painful inflamed eardrum
(otitis media), or
tonsillopharyngitis without
features of viral infection
(e.g. coryza, cough)
Laboratory studies if
available, e.g. culture of
suitable body fluid
Persistent generalized
lymphadenopathy
Histology
CLINICAL STAGE 2
Herpes zoster
Angular cheilitis
Painful vesicular rash in
dermatomal distribution of
a nerve supply does not
cross midline
Splits or cracks at the angle
of the mouth not
attributable to iron or
vitamin deficiency, and
1. Natural History of HIV Infection – Clinician Sept06 V
Clinical diagnosis
Clinical diagnosis
Source: Clinician Software 2006
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usually responding to
antifungal treatment
Recurrent oral ulcerations Aphthous ulceration,
typically painful with a halo
(two or more episodes in
of inflammation and a
last six months)
yellow-grey
pseudomembrane
Clinical diagnosis
Papular pruritic eruption
Papular pruritic lesions,
often with marked
postinflammatory
pigmentation
Clinical diagnosis
Seborrhoeic dermatitis
Itchy scaly skin condition,
particularly affecting hairy
areas (scalp, axillae, upper
trunk and groin)
Clinical diagnosis
Fungal nail infections
Paronychia
(painful red and swollen
nail bed) or onycholysis
(separation of nail from nail
bed) of the fingernails
(white discolouration,
especially involving
proximal part of nail plate,
with thickening and
separation of nail from
nail bed)
Fungal culture of nail / nail
plate material
CLINICAL STAGE 3
CLINICAL EVENT
CLINICAL DIANGOSIS
Severe unexplained weight Reported unexplained
weight loss (over 10% of
loss (more than 10% of
body weight) and visible
body weight)
thinning of face, waist and
extremities with obvious
wasting or body mass index
below 18.5. In pregnancy,
weight loss may be masked
Unexplained chronic
diarrhoea for longer than
Chronic diarrhoea (loose or
watery stools three or more
1. Natural History of HIV Infection – Clinician Sept06 V
DEFINITE DIAGNOSIS
Documented loss of more
than 10% of body weight
Not required but confirmed
if three or more stools
Source: Clinician Software 2006
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one month
times daily) reported for
longer than one month
observed and documented
as unformed, and two or
more stool tests reveal no
pathogens
Unexplained persistent
fever (intermittent or
constant and lasting for
longer than one month)
Reports of fever or night
sweats for more than one
month, either intermittent or
constant with reported lack
of response to antibiotics or
antimalarials, without other
obvious foci of disease
reported or found on
examination. Malaria must
be excluded in malarious
areas.
Documented fever
exceeding 37.6 oC with
negative blood culture,
negative Ziehl-Nielsen (ZN)
stain, negative malaria
slide, normal or unchanged
chest X-ray (CXR) and no
other obvious focus of
infection
Oral candidiasis
Persistent or recurring
creamy white curd-like
plaques which can be
scraped off
(pseudomembranous), or
red patches on tongue,
palate or lining of mouth,
usually painful or tender
(erythematous form)
Clinical diagnosis
Oral hairy leukoplakia
Fine white small linear or
corrugated lesions on lateral
borders of the tongue,
which do not scrape off
Clinical diagnosis
Pulmonary TB
(current)
Chronic symptoms (lasting
at least two to three weeks):
cough, haemoptysis,
shortness of breath, chest
pain, weight loss, fever,
night sweats, PLUS either
positive sputum smear
OR
negative sputum smear
AND compatible chest
radiograph (including but
not restricted to upper lobe
infiltrates, cavitation,
pulmonary fibrosis and
Isolation of M. tuberculosis
on sputum culture or
histology of lung biopsy
(together with compatible
symptoms)
1. Natural History of HIV Infection – Clinician Sept06 V
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shrinkage). No evidence of
extrapulmonary disease.
Severe bacterial infection
(e. g. pneumonia,
meningitis, empyema,
pyomyositis, bone or joint
infection, bacteraemia,
severe pelvic
inflammatory disease )
Fever accompanied by
specific symptoms or signs
that localize infection, and
response to appropriate
antibiotic
Isolation of bacteria from
appropriate clinical
specimens (usually sterile
sites)
Acute necrotizing
ulcerative gingivitis or
necrotizing ulcerative
periodontitis
Severe pain, ulcerated
gingival papillae, loosening
of teeth, spontaneous
bleeding, bad odour, rapid
loss of bone and/or soft
tissue
Clinical diagnosis
Unexplained anaemia
(below 8g/dl ),
neutropenia (below 0.5 ×
109/l) or chronic (more
than one month)
thrombocytopenia
(under 50 × 109/l)
No presumptive clinical
diagnosis
Diagnosed on laboratory
testing and not explained by
other non-HIV conditions.
Not responding to standard
therapy with haematinics,
antimalarials or
anthelmintics as outlined in
relevant national treatment
guidelines, WHO IMCI
guidelines or other relevant
guidelines.
CLINICAL DIANGOSIS
DEFINITE DIAGNOSIS
Unexplained involuntary
weight loss (over 10% of
body weight) with obvious
wasting or body mass index
below 18.5
Documented weight loss
(over 10% of body weight)
CLINICAL STAGE 4
CLINICAL EVENT
HIV wasting syndrome
plus
PLUS EITHER
two or more unformed
stools negative for
pathogens
unexplained chronic
diarrhoea (loose or watery
stools three or more times
OR
1. Natural History of HIV Infection – Clinician Sept06 V
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daily) reported for longer
than one month
OR
reports of fever or night
sweats for more than one
month without other cause
and lack of response to
antibiotics or antimalarials.
Malaria must be excluded in
malarious areas.
CLINICAL EVENT
Dyspnoea on exertion or
nonproductive cough of
recent onset (within the past
three months), tachypnoea
and fever; AND CXR
evidence of diffuse bilateral
interstitial infiltrates, AND
no evidence of bacterial
pneumonia, bilateral
crepitations on auscultation
with or without reduced air
entry.
documented temperature
exceeding 37.6 oC with no
other cause of disease,
negative blood culture,
negative malaria slide and
normal or unchanged CXR
Recurrent bacterial
pneumonia
(this episode plus one or
more episodes in last six
months)
Current episode plus one or
more episodes in last six
months. Acute onset (under
two weeks) of symptoms
(e.g. fever, cough,
dyspnoea, and chest pain)
PLUS new consolidation on
clinical examination or
CXR. Response to
antibiotics.
Positive culture or antigen
test of a compatible
organism
Chronic herpes simplex
virus (HSV) infection
(orolabial, genital or
anorectal) of more than
one month, or visceral of
any duration
Painful, progressive
anogenital or orolabial
ulceration; lesions caused
by recurrent HSV infection
and reported for more than
one month. History of
previous episodes. Visceral
HSV requires definitive
diagnosis.
Positive culture or DNA (by
PCR) of HSV or compatible
cytology/histology
Oesophageal candidiasis
Recent onset of retrosternal
Macroscopic appearance at
Pneumocystis pneumonia
1. Natural History of HIV Infection – Clinician Sept06 V
Cytology or
immunofluorescent
microscopy of induced
sputum or bronchoalveolar
lavage (BAL), or histology
of lung tissue.
Source: Clinician Software 2006
Based on Scaling up HIV Treatment in Resource Limited Settings: WHO Guidelines, 2006
Extrapulmonary TB
Kaposi sarcoma
CLINICAL DIAGNOSIS
DEFINITIVE
DIAGNOSIS
CMV disease (other than
liver, spleen or lymph
node)
CLINICAL EVENT
CNS toxoplasmosis
18
pain or difficulty on
swallowing (food and
fluids) together with oral
candidiasis
Systemic illness (e.g. fever,
night sweats, weakness and
weight loss). Other
evidence for
extrapulmonary or
disseminated TB varies by
site: pleural, pericardial,
peritoneal involvement,
meningitis, mediastinal or
abdominal
lymphadenopathy or
osteitis.
Discrete peripheral lymph
node M. tuberculosis
infection is considered a
less severe form of
extrapulmonary
tuberculosis.
endoscopy or
bronchoscopy, or by
microscopy/histology
Typical appearance in skin
or oropharynx of persistent,
initially flat patches with a
pink or blood-bruise colour,
skin lesions that usually
develop into violaceous
plaques or nodules.
Macroscopic appearance at
endoscopy or
bronchoscopy, or by
histology.
Retinitis only: may be
diagnosed by experienced
clinicians. Typical eye
lesions on fundoscopic
examination: discrete
patches of retinal whitening
with distinct borders,
spreading centrifugally,
often following blood
vessels, associated with
retinal vasculitis,
haemorrhage and necrosis.
Compatible histology or
CMV demonstrated in CSF
by culture or DNA (by
PCR)
Recent onset of a focal
neurological abnormality or
Positive serum toxoplasma
antibody AND (if available)
1. Natural History of HIV Infection – Clinician Sept06 V
M. tuberculosis isolation or
compatible histology from
appropriate site
OR
radiological evidence of
miliary TB (diffuse
uniformly
distributed small miliary
shadows or micronodules
on CXR.
Source: Clinician Software 2006
Based on Scaling up HIV Treatment in Resource Limited Settings: WHO Guidelines, 2006
reduced level of
consciousness AND
response within ten days to
specific therapy.
19
single/multiple intracranial
mass lesion on
neuroimaging (CT or MRI)
HIV encephalopathy
Clinical finding of disabling Diagnosis of exclusion, and,
cognitive and/or motor
if available, neuroimaging
dysfunction interfering with (CT or MRI)
activities of daily living,
progressing over weeks or
months in the absence of a
concurrent illness or
condition, other than HIV
infection, which might
explain the findings.
Extrapulmonary
cryptococcosis (including
meningitis)
Meningitis: usually
subacute, fever with
increasingly severe
headache, meningism,
confusion, behavioural
changes that respond to
cryptococcal therapy
Isolation of Cryptococcus
neoformans from
extrapulmonary site or
positive cryptococcal
antigen test (CRAG) on
CSF/blood
Disseminated
nontuberculous
mycobacteria
infection
No presumptive clinical
diagnosis
Diagnosed by finding
atypical mycobacterial
species from stool, blood,
body fluid or other body
tissue, excluding lung
Progressive multifocal
leukoencephalopathy
(PML)
No presumptive clinical
diagnosis
Progressive neurological
disorder (cognitive
dysfunction, gait/speech
disorder, visual loss, limb
weakness and cranial nerve
palsies) together with
hypodense white matter
lesions on neuroimaging or
positive polyomavirus JC
(JCV) PCR on CSF
Cryptosporidiosis (with
diarrhoea lasting more
than
one month)
No presumptive clinical
diagnosis
Cysts identified on
modified
ZN microscopic
examination of unformed
stool.
1. Natural History of HIV Infection – Clinician Sept06 V
Source: Clinician Software 2006
Based on Scaling up HIV Treatment in Resource Limited Settings: WHO Guidelines, 2006
20
Chronic isosporiasis
No presumptive clinical
diagnosis
Identification of Isospora
Disseminated mycosis
(coccidiomycosis,
histoplasmosis)
No presumptive clinical
diagnosis
Histology, antigen detection
or culture from clinical
specimen or blood culture
Recurrent non-typhoid
salmonella bacteraemia
No presumptive clinical
diagnosis
Blood culture
Lymphoma (cerebral or B
cell non-Hodgkin) or
other solid HIVassociated tumours
No presumptive clinical
diagnosis
Histology of relevant
specimen or, for CNS
tumours, neuroimaging
techniques
Invasive cervical carcinoma
No presumptive clinical
diagnosis
Histology or cytology.
Invasive cervical
carcinoma
No presumptive clinical
diagnosis
Histology or cytology.
Visceral leishmaniasis
No presumptive clinical
Diagnosis
Histology (amastigotes
visualized) or culture from
any appropriate clinical
specimen
HIV-associated
nephropathy
No presumptive clinical
diagnosis
Renal biopsy
HIV-associated
cardiomyopathy
No presumptive clinical
diagnosis
Cardiomegaly and evidence
of poor left ventricular
function confirmed by
echocardiography
Source: Antiretroviral Therapy of Adults and Adolescents in Resource Limited Settings: Towards Universal
Access. WHO 2006 V
1. Natural History of HIV Infection – Clinician Sept06 V
Source: Clinician Software 2006