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National Medicines
Information Centre
VOLUME 18
NUMBER 4
2012
ST. JAMES’S HOSPITAL • DUBLIN 8
TEL 01-4730589 or 1850-727-727 • FAX 01-4730596 • www.nmic.ie
HUman immunodeficiency virus infection
Human immunodeficiency virus (HIV) is transmitted by sexual contact (heterosexual and male to male),
by blood and blood products and by infected mothers to infants
Delayed diagnosis of HIV is associated with increased morbidity and mortality, therefore testing of
HIV should be undertaken for all patients at risk of HIV infection and for pregnant women; increased
targeted testing in areas of high prevalence shoud be considered
Antiretroviral therapy (ART) is very effective at reducing morbidity and mortality in patients infected
with HIV and results in patients having a normal quality of life and attaining life goals
Healthcare professionals should be aware of the potential for drug-drug interactions in patients on ART
INTRODUCTION
Acquired Immune Deficiency Syndrome (AIDS) was first recognised in the US in 1981, with cases of Pneumocystis jiroveci
pneumonia and/or Kaposi’s sarcoma being reported in previously healthy men who have sex with men (MSM). The disease
subsequently became recognised in injection drug users (IDUs), in recipients of blood transfusions and in haemophiliacs.1 In
1983 human immunodeficiency virus (HIV) was isolated from a patient with lymphadenopathy and in 1984 it was demonstrated
to be the causative agent of AIDS, which had a high mortality.1,2 With the arrival of highly active antiretroviral therapy (ART),
the mortality from HIV reduced; it is now considered a chronic medical condition. The majority of patients living with HIV in
developed countries, remain fit and well.2,3 However many HIV-infected people remain unaware of their HIV status, continue to
transmit HIV to others and when diagnosed have very advanced and often difficult to treat late stage disease.1-3 This bulletin will
provide an overview of HIV infection.
EPIDEMIOLOGY
HIV infection/AIDS is a global pandemic, with an estimated 34.2 million individuals living with HIV in 2011, of which 2.5
million people were newly diagnosed.1,4 The most common HIV infection in the world is HIV-1; HIV-2 is mainly found in West
Africa but remains less common overall.1 HIV is transmitted primarily by sexual contact (both heterosexual and in MSM), by
blood and blood products and by infected mothers to infants.1 Maternal transmission of HIV to the foetus occurs most commonly
in the perinatal period. Risk factors associated with an increased risk of sexual transmission of HIV include: behavioural changes
associated with alcohol consumption and illicit drug use, and unsafe sexual behaviour. The risk of HIV transmission is highest
in the first weeks of HIV infection, before and around seroconversion, when plasma HIV RNA levels are high and in
advanced disease as the viral load increases.1 There is a small but definite occupational risk of HIV transmission to healthcare
workers and laboratory personnel, which is reduced with use of ART following exposure, i.e. post exposure prophylaxis (PEP).
In Ireland, it is estimated that the diagnosed prevalence of HIV in adults aged 17-78 years is approximately 1 in 1,000 nationally
and 2 in 1,000 in Dublin.5 In 2011, there were 320 people (74% male) newly diagnosed with HIV, 46 patients diagnosed with
AIDS and 7 reported deaths among AIDS cases.6 Of those newly diagnosed with HIV, 43% were MSM, 34% were heterosexuals,
5% were IDUs and 1% (n=3) were reported as mother to child transmission. Overall the largest number of new HIV cases
occurred in those aged 30-39 years, and people ≥50 years accounted for 10 % of new diagnoses.
Pathophysiology
HIV is a single stranded RNA retrovirus. Extracellular virions enter their target cell through a complex three-step process, (1)
attachment to the CD4 receptor, (2) binding to the CCR5 or CXCR4 co-receptors, or both and (3) membrane fusion.2 The hallmark
of HIV disease is a profound immunodeficiency resulting primarily from a progressive quantitative and qualitative deficiency
of the subset of T lymphocytes referred to as helper T cells. HIV binds to CD4 receptors on helper T lymphocytes, monocytes,
macrophages and neural cells.7 CD4 infected cells migrate to the lymphoid tissue where the virus replicates producing billions of
new virions. These are released and in turn infect new CD4 cells. The progressive and severe depletion of CD4 helper lymphocytes
has profound repercussions for the functioning of the immune system. Cell-mediated immune deficiency, which is the major
consequence, leaves the host open to infections with intracellular pathogens, while the coexisting antibody abnormalities
predispose to infections with encapsulated bacteria. HIV also has a direct effect on certain tissues, including the nervous system.
Clinical presentation
Primary HIV infection is often asymptomatic and the majority of patients are unaware of seroconversion. It is estimated that 1050% of patients experience an acute retroviral syndrome characterised by fever, malaise, generalised lymphadenopathy, pharyngitis,
diarrhoea and rash typically 2-4 weeks after infection, which resolves spontaneously within 2-3 weeks.1,2 All patients will develop
some degree of viraemia during infection, which contributes to virus dissemination throughout the lymphoid tissue, even though
they may be asymptomatic or not recall experiencing symptoms.1 In primary infection, plasma HIV RNA concentrations can
be very high, making secondary transmission a high risk if the newly infected person continues to engage in unprotected
sexual activity or needle sharing.2,3 Up to 50% of all transmission events in MSM are thought to occur in the context of acute
infection, therefore identification, treatment and counselling of affected individuals is a key public health focus.2
Clinically asymptomatic disease: After the symptoms of primary HIV infection resolve, the infected person enters a phase of
clinically asymptomatic disease, which may persist for a median of 10 years.1 Rapid progression may also occur, which is more
commonly associated with older age.2 The virus continues to replicate and the person remains infectious. Symptomatic disease
often emerges as the peripheral CD4 cell count falls to <350 cells per µL.2
Advanced HIV disease: As HIV infection progresses, the viral load rises, the CD4 count falls and the patient becomes highly
susceptible to opportunistic disease.1 Although the CD4 lymphocytes are the principal targets of HIV, virtually any cell that
expresses the CD4 molecule can potentially be infected with HIV.1 HIV-associated diseases include cytomegalovirus (CMV)
infection, Kaposi’s sarcoma, HIV encephalopathy, herpes simplex and recurrent or multiple bacterial infections. The risk of
HIV-associated disease becomes apparent at low CD4 cell counts, with many occurring at <200 cells per µL (e.g. Pneumocystis
pneumonia, cerebral toxoplasmosis).1,2 However serious complications including bacterial pneumonia, Kaposi’s sarcoma, nonHodgkins lymphoma and tuberculosis (TB) may occur in patients with higher CD4 cell counts.2
Diagnosis
It is important to diagnose patients with HIV early, as late diagnosis has been associated with increased transmission of HIV,
increased morbidity and mortality, impaired response to ART and increased cost to healthcare services.3 A recent UK study found
that 24% of deaths occurring amongst HIV positive patients were directly attributable to the diagnosis of HIV being made
too late for effective treatment.3 Of interest, many of these patients had previously been seen by healthcare professionals, prior
to the diagnosis of HIV being made. Universal routine (‘opt-out’) strategies have been adopted in healthcare settings, whereby
all individuals attending specific settings are offered and recommended HIV testing as part of routine care, but an individual has
the option to refuse a test.3 These settings include antenatal clinics, sexual health clinics and patients diagnosed with conditions
including TB, hepatitis B and lymphoma. The adoption of universal testing in the antenatal setting has resulted in a significant
reduction in the proportion of patients with HIV that remain undiagnosed prior to delivery.3 Voluntary antenatal HIV testing in
Ireland was introduced in 1999, and since then all women who attend for antenatal services are offered screening.8 Testing of HIV is
recommended for other patients as outlined in Table 1. As with any other medical investigation, the patient should be informed that
a HIV test is being performed; however lengthy HIV counselling is not a requirement unless requested by the patient.3
Table 1: Settings in which HIV testing should be undertaken or considered3
Universal HIV testing is recommended in all the following settings:
• Sexual health clinics
• Antenatal services
• Drug dependency services
• Healthcare services for those diagnosed with TB, hepatitis B, hepatitis C and lymphoma
HIV testing should be routinely offered and recommended to the following group of patients
• All patients presenting to healthcare settings where HIV, including primary HIV is part of the differential diagnosis
• All patients diagnosed with a sexually transmitted infection
• All sexual partners of men and women known to be HIV positive
• All men who have disclosed sexual contact with other men
• All female sexual contacts of men who have sex with men
• All patients reporting a history of injecting drug abuse
• All men and women known to be from a country of high HIV prevalence (>1%)*
• All men and women who report sexual contact abroad or at home with individuals from countries of high HIV prevalence
HIV testing should be routinely performed in the following groups
• Blood donors
• Dialysis patients
• Organ transplant donors and recipients
HIV testing may be considered in the following settings where the diagnosed HIV prevalence in the local population exceeds 2 in 1,000 of the
population**
• All men and women visiting their general practitioner
• All general medical admissions
The introduction of universal HIV testing in these settings should be evaluated for acceptability and feasibility and the resultant data made
available to inform the ongoing development of guidelines.
*for an up-to-date list see http://www.unaids.org/en/knowledgeCentre/HIVData/Epidemiology/LatestEpiData.esp,
** - e.g. greater Dublin area according to 2010 figures
HIV is diagnosed by a positive result of a HIV screening antibody test or a combined screening test (HIV antibody and HIV p24
antigen) and confirmed by a more specific antibody test (e.g. Western blot).9 HIV antibody might be initially negative following
recent infection (usually 1-3 weeks after exposure) and in this case checking HIV nucleic acid (HIV-RNA, HIV-DNA) or repeating
antibody tests at 6 weeks and 3 months can confirm the diagnosis. Confirmation of HIV requires two positive results on two
separate samples. In Ireland, confirmatory tests are undertaken by The National Virus Reference Laboratory (NVRL). Since 1st
January 2012, all confirmed cases of HIV must be notified to the Department of Public Health.9
Management of hIV
The aims of management of patients with HIV infection are (1) to maintain physical and mental health, (2) to avoid transmission
of the virus and (3) to maximise quality of life. The complexity of HIV infection means that patients should be managed
by physicians with HIV expertise and via a multidisciplinary team approach. Contact tracing is an important aspect of the
non-pharmacological management of a patient with HIV, which should be undertaken by a trained health advisor.9 Managing
patients with sensitivity and taking care to address their fears which may be heightened due to the stigma associated with HIV, are
central elements to effective contact tracing and secondary prevention. Patients must be educated about the potential transmissibility
of their infection and they should be counselled with regard to sexual practices and needle sharing.1 Psychological and emotional
support of the infected patient, the family and friends are also vital aspects of the management.
Pharmacological Management
Combination ART, also referred to as highly active ART (HAART), is the cornerstone of management of patients with HIV.1
Successful ART is associated with dramatic decreases in the development of HIV-related conditions and their associated
mortality.1,10 Widespread use of ART during pregnancy has almost eliminated mother to child transmission in the developed world.10
Recent data from the UK has shown that life expectancy in people treated for HIV infection has increased by over 15 years during
1996-2008, but is still about 13 years less than that of the UK population.11 It is considered that earlier diagnosis and subsequent
timely treatment with ART may further increase life expectancy. There is ongoing research as to the most appropriate time
to start ART,2,12,13 however recent evidence increasingly supports earlier initiation of ART.13 Studies have shown a decrease in
AIDS-free survival as the CD4 count threshold for initiation of therapy decreases and the higher the CD4 cell count achieved after
commencing ART, the greater the survival benefit.13 The British HIV Association guidelines currently recommend ART for patients
including those with chronic HIV infection presenting with CD4 cell count ≤350 cells per µL; those presenting with HIV-associated
disease (e.g. Kaposi’s sarcoma) irrespective of CD4 cell count; patients presenting with primary HIV infection and with one of the
following criteria: neurological involvement; and patients with HIV presenting either with an AIDS-defining infection, or a serious
bacterial infection and a CD4 cell count <200 cells per µL.12 In addition, to reduce the risk of mother to child transmission, pregnant
women should be treated at least by the second trimester and therapy continued after birth.10 The early initiation of ART also reduces
the rate of transmission in serodiscordant relationships of HIV by up to 96%, which is another indication to consider treatment with
ART.14
Virological treatment failure is generally defined as persistently detectable plasma HIV RNA concentrations after 16-24 weeks of
ART. Nearly all first regimen virological failures can be attributed to non-adherence or pre-existing drug resistance.2 The treatment
goal is to reduce viral load to undetectable ranges.2 Virological failure should trigger a thorough review of drug side-effects (a
common cause of non-adherence) and a search for other drugs and medical conditions that may be affecting absorption or
metabolism of ART.
Patients with HIV also require treatment for opportunistic infections which may occur e.g. CMV, TB, herpes simplex and any
co-existing co-morbidities.
Antiretroviral agents used in hiv
ART drugs are classified by the viral life-cycle step they inhibit and/or by their chemical structure.2 Due to concerns regarding
resistance, three active drugs are usually used in combination for the treatment of HIV. Initial therapy usually consists of a backbone
of two nucleoside/nucleotide reductase inhibitors (NRTIs) and a third drug (either a protease inhibitor [PI], or a non-nucleoside
reductase inhibitor [NNRTI] or an integrase inhibitor).2,13 Irish figures estimate that 43% of patients on ART are on first-line NRTIs
and a NNRTI and another 43% are on NRTIs and a PI.5 The most popular regimen in terms of convenience, is a coformulation of
three drugs in a single pill take once daily.2 Table 2 summarises the ART drugs used in clinical practice.
Table 2: Antiretroviral drugs used in clinical practice12,13,15-38
Class
Drugs
Precautions for use *
Nucleoside and
nucleotide reverse
transcriptase inhibitors
(NRTIs)
Abacavir
Didanosine
Emtricitabine
Lamivudine
Stavudine
Tenofovir
Zidovudine
All NRTIs are associated with potential risk of severe lactic acidosis and hepatic steatosis; should be
used with caution in patients at risk of or with hepatic dysfunction. Dose adjustments are recommended
in renal impairment, apart from abacavir
Abacavir is associated with hypersensitivity reactions in at risk individuals (i.e. HLA B5701 positive
patients) and some studies show an association with its use and myocardial infarction
Tenofovir is associated with renal dysfunction and a decrease in bone mineral density
Zidovudine is associated with haematological adverse reactions
Stavudine has been associated with peripheral neuropathy and lipoatrophy
Didanosine has been associated with peripheral neuropathy and pancreatitis
Efavirenz, etrevirine and nevirapine are associated with development of maculopapular rash and also
the development of Stevens’ Johnson syndrome (SJS)
Efavirenz can cause CNS toxicity (which is usually time limited) and has teratogenic potential
Etravine is associated with severe hypersensitivity reactions
Nevirapine can cause hepatotoxicity when used in patients with higher CD4 cell counts.
Rilpivirine has substantial food interactions
Non-nucleoside reverse Efavirenz
transcriptase inhibitors Etravirine
(NNRTIs)
Nevirapine
Rilpivirine
Protease inhibitors
(PIs)
Atazanavir
Darunavir
Fosamprenavir
Indinavir
Lopinavir
Nelfinavir
Ritonavir
Saquinavir
Tipranavir
Most PIs are associated with hyperlipidaemia and other metabolic abnormalities such as insulin
resistance. Long term PI exposure has been associated with an increased risk of cardiovascular disease
Atazanavir is associated with QT prolongation, increased bilirubin and occasionally causes reversible
jaundice
Darunavir has been associated with drug induced hepatitis and skin rash which may be severe (including
SJS)
Fosamprenavir is associated with a rash
Indinavir is associated with an increased risk of nephrolithiasis
Lopinavir is associated with an increased risk of pancreatitis
Nelfinavir should be used with caution in patients with liver disease
Ritonavir has been associated with prolonged QT interval and pancreatitis
Saquinivir is associated with dose-dependent QT and PR prolongations; contraindicated in patients
with QT prolongation and in patients on drugs which prolong QT and/or PR interval
Tipranavir has been associated with drug induced hepatitis and an increased risk of bleeding including
reports of intracranial haemorrhage
Integrase inhibitors
Raltegravir
Severe skin and hypersensitivity reactions have been reported
Other agents:
CCR5 inhibitors
Maraviroc
Entry inhibitors
Enfuvirtide
Cases of hepatotoxicity and hepatic failure with allergic features have been reported. Caution in severe
cardiovascular disease
Injection site reactions and hypersensitivity reactions occur with enfuvirtide
* This list is not exhaustive; the individual Summary of Product Characteristics should be consulted for full prescribing information including further information
on precautions, adverse effects and drug interactions for each medicine
Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) block the action of reverse transcriptase thereby preventing further
synthesis of viral DNA, resulting in inhibition of HIV replication.1,39,40 The currently available NRTIs are nucleoside RTIs, apart from
tenofovir, which is a nucleotide RTI.1,40 NRTIs are not metabolised by the CYP450 system, however drug interactions can
occur as many of the NRTIs are exclusively eliminated by the kidneys.40 Abacavir should only be used in HIV patients who have
been screened for HLA-B5701, due to hypersensitivity reactions which occur more commonly in patients who are HLA-B5701
positive.1,10,16 Lamivudine, emtricitabine and tenofovir also have activity against hepatitis B (Hep B) virus.1,10,15 Recurrent hepatitis
in patients with Hep B may occur on discontinuation of these NRTIs, therefore patients require liver function monitoring.15 The
combination of tenofovir and emtricitabine or abacavir and lamivudine as alternatives are the preferred ‘backbone’ first-line treatment
in most regions.2,12,13
Non-nucleoside reverse transcriptase inhibitors (NNRTIs) inhibit HIV-1 reverse transcriptase, by binding to the enzyme outside
the active site and causing changes in the enzyme that render it inactive.39 They are used as combination ART for the treatment
of HIV-1 infected patients. A limitation to their use is that they are metabolised by the CYP450 system which leads to potential
numerous drug-drug interactions (DDIs).39 All NNRTIs are substrates for CYP3A4 and can act as inducers, inhibitors or mixed
inducers and inhibitors. Efavirenz is the most common NNRTI used as a third agent in combination ART.12
Protease inhibitors (PIs) prevent the processing of viral proteins into functional conformations, resulting in immature, noninfectious viral particles.39 PIs are used as combination ART for the treatment of HIV-1 infected patients.1 All the PIs are extensively
metabolised by CYP3A4 and there is enormous potential for DDIs with other ART and other commonly used medications.39
Ritonavir has the most pronounced inhibitory CYP450 effect. This effect is used to clinical advantage to “boost” the levels of other
PI agents (by inhibiting their metabolism). Boosted atazanavir (i.e. combined with ritonavir) or darunavir may be used as the ‘third
agent’ in initial combination ART.12
Integrase inhibitors which inhibit the viral enzyme integrase are the newest class of ART. Raltegravir is authorised for use as
combination therapy for HIV-1 patients.36 Raltegravir does not affect the CYP450 system.36 It can be used as the ‘third agent’ in
initial ART.2
Other ART agents used: A number of other ART agents are used in highly specialised settings including CCR5 antagonists
(interfere with HIV binding at the stage of co-receptor engagement) and entry (fusion) inhibitors (interfere with HIV binding to
its receptor or co-receptor).1 Maraviroc (CCR5 antagonist) is authorised in combination therapy for treatment experienced patients
infected with CCR5-tropic HIV-1 infection.37 It is a substrate for CYP3A4 and requires adjustment in the presence of drugs
that interact with these enzymes.37 Enfuvirtide (entry inhibitor), which is administered twice daily subcutaneously, is authorised
for use as combination therapy in HIV-1 patients who have failed or have intolerance of other regimes.38 No clinically significant
DDIs are expected between enfuvirtide and concurrently given medicinal products metabolised by CYP450 enzymes.38
drug interactions associated with Antiretroviral therapy
Clinically significant DDIs between ART and other drugs occur frequently in clinical practice, primarily due to induction or
inhibition of the CYP450 system. It is estimated that approximately 25-33% of patients receiving ART are at risk of a clinically
significant DDI.12
HIV specialists are responsible for initiating and monitoring HIV patients on ART, however HIV patients are increasingly being
managed by non-HIV specialists for co-morbid conditions.41 Studies suggest that physicians may only be able to correctly identify
a third of clinically significant DDIs involving ART.12,41 This emphasises the importance of being aware of what medications the
patient is taking, the possibility of DDIs occurring in patients on ART and of good communication amongst healthcare professionals.
It is important that patients are educated on the risks of DDIs including over-the-counter or recreational drugs. Patients should be
encouraged to check with their healthcare professionals before commencing any new drugs.
Evidence suggests that HIV patients receiving ART take between 6-10 medications and that the risk of a clinically significant
DDI is higher among patients using > 5 non-antiretroviral agents.41 Clinically important DDIs to consider when co-administering
with ART include interactions with the following drugs: methadone, oral contraceptives, anti-epileptics, antidepressants, lipidlowering agents, acid-reducing agents, certain antimicrobials (e.g. clarithromycin, minocycline and fluconazole), some
anti-arrhythmics, TB therapy, anti-cancer drugs, immunosuppressants, phosphodiesterase inhibitors and anti-hepatitis C
virus therapy. Most of these interactions can be managed safely (i.e. with/without dosage modification, together with enhanced
clinical vigilance) but in some cases the nature of the interaction is such that co-administration must be avoided (e.g ribavirin
and zidovudine, atazanavir and proton pump inhibitors, PIs and rifampicin, PIs and dabigatran/rivaroxaban, PIs and triazolam).42
An excellent resource for healthcare professionals, developed by the University of Liverpool, is www.hiv-druginteractions.org,
which provides clinically useful, reliable, up-to-date, evidence-based information on DDIs in HIV treated patients.41 The
website has interaction charts for the different types of ART, which are also available as a mobile phone app.
Practical issues in managing a patient with HIV
It is important that there are clear procedures for patients to receive a confirmed diagnosis of HIV.3 A newly-diagnosed patient should
be immediately linked into appropriate HIV treatment and care.3 Patients need to be assessed for other co-morbidities including
cardiovascular disease. Modifiable cardiovascular risk factors should be addressed in all patients with HIV infection.10
Drug adherence: Poor adherence to ART can affect HIV-related outcomes such as viral load, progression to AIDS and survival
and can be improved by various interventions.43,44 For most patients on ART, near perfect adherence of >95% is required to achieve
full and durable viral suppression.45 Studies have shown that educating patients about ART (including necessity, efficacy and sideeffects) all affect adherence.12 Depression is significantly associated with low adherence and some studies report an independent
association between depression and mortality in people with HIV. Additional factors which have a negative effect on adherence
include problematic alcohol and recreational drug use, poverty, youth and female gender.
Adverse effects: It is important to consider adverse effects of ART; all presently used ARTs are generally well tolerated and safe, but
none are without adverse effects.2 Improvement in immune function as a result of ART may provoke a marked inflammatory reaction
against residual opportunistic organisms, i.e. immune restitution syndrome (IRIS). Metabolic effects associated with ART include
fat redistribution, insulin resistance and dyslipidaemia (lipodystrophy syndrome).15 Fat redistribution is associated with regimens
containing PIs and NRTIs. Dyslipidaemia is associated with ART, particularly PIs and insulin resistance and hyperglycaemia is
associated with PIs and some NRTIs.15 Osteonecrosis has been reported in patients with advanced HIV diseases or following longterm exposure to combination ART.
Monitoring: Baseline investigations will depend on the clinical setting, but should include a full blood count, urea and electrolytes,
liver function tests, lipid profile, lymphocyte subsets, HIV viral load and a screen for other sexually transmitted infections. Plasma
lipids and blood glucose should be monitored 3 to 6 months after starting ART and annually.15 The average CD4 cell count in
uninfected adults is usually >500 cells per µL. Most opportunistic infections and cancers occur as the CD4 cell count falls <200 cells
per µL.2 Once treatment has begun, CD4 cells typically increase rapidly for the first three months and then slowly increase. The viral
load is measured before ART begins, but its primary value is in monitoring the treatment response or failure. The treatment goal is
to reduce viral load to undetectable ranges. CVD risk factors should be assessed in all patients annually and fracture risk in patients
≥50 years every 3 years.46
Drug resistance testing: Most guidelines recommend obtaining a baseline genotypic resistance test once HIV infection is diagnosed
and in patients who experience virological failure while on ART.2 Each ART drug and to some degree each drug class, varies in its
ability to generate drug resistance. Full resistance to some drugs follows the selection of one mutation (e.g. most NNRTIs), while
other drugs retain some activity even after some mutations have emerged (e.g. NRTIs). PIs typically have a high genetic barrier and
need long-term exposure before resistance emerges.
SUMMARY
Delayed diagnosis of HIV is associated with increased morbidity and mortality, therefore testing of HIV should
be undertaken for all patients at risk of HIV infection and for pregnant women; increased targeted testing in
areas of high prevalence should be considered
• Confirmation of a diagnosis of HIV requires two positive results on two separate samples
• Patients with HIV should be referred to a HIV specialist and multidisciplinary team
• The use of ART in a patient with HIV is associated with reduced morbidity and mortality
• Poor adherence to ART can have an impact on the outcome of a patient with HIV and patients should be
educated on the importance of adherence to ART regimens
• Many of the ART agents used to treat patients with HIV have the potential to cause significant DDIs
• Many patients will have co-morbid conditions requiring additional co-medication with the potential increased
risk for a DDI
• www.hiv-druginteractions.org is an excellent resource, which provides clinically useful, reliable, up-to-date,
evidence-based information on DDIs in patients with HIV on ART
FOR PERSONAL USE ONLY. NOT TO BE REPRODUCED WITHOUT PERMISSION OF THE EDITOR
•
List of references available on request. Date of preparation: November 2012
Every effort has been made to ensure that this information is correct and is prepared from the best available resources at our disposal at the time of issue.
Prescribers are recommended to refer to the individual Summary of Product Characteristics (SmPC) for specific information on a drug.
References for HIV Bulletin Vol 18 No 4 2012
1. Human Immunodeficiency Virus Disease: AIDS and Related Disorders, Section 14, chapter
189, Harrison’s Principles of Internal Medicine, Edited by Longo D. Fauci A, Kasper D,
Hauser S et al, 18th Edition published by the McGraw Hill companies 2012
2. Volberding P, Deeks S, Antiretroviral therapy and management of HIV infection, Lancet
2010;376:49-62
3. British HIV Association & British Association of Sexual Health and HIV British Infection
society, UK National Guidelines for HIV testing 2008, downloaded from www.bashh.org on
the 9th August 2012
4. WHO factsheet, Global summary of the AIDS epidemic 2011, downloaded from
www.who.int on the 10th October 2012
5. Tuite H et al, Antiretroviral treatment and viral responses in HIV-infecetd patients accessing
specialist care in Ireland, in 22nd European Congress of Clinical Microbilogy and Infectious
Diseases (ECCMID), 31.03.2012 – 03.04.2012 available at
http://registration.akm.ch/einsicht.php?XNABSTRACT_ID=145623&XNSPRACHE_ID=2
&XNKONGRESS_ID=161&XNMASKEN_ID=900
6. HPSC, HIV in Ireland 2011 Report, published May 2012, downloaded from www.hpsc.ie on
the 3rd October 2012
7. Oxford textbook
8. Epi-Insight Voluntary Antenatal HIV testing in Ireland: Results of the screening programme
2002-2008 April 2010, downloaded from www.hpsc.ie on the 10th October 2012
9. A working group of the National AIDS Strategy Committee, HIV notification – Information
for professionals, published June 2012, downloaded from www.hpsc.ie on the 15th October
2012
10. Thompson M, Aberg J, Cahn P et al, Antiretroviral treatment of adult HIV infection, 2012
recommendations of the international AIDS Society-USA panel, JAMA 2010;304 (3):321333
11. Mat M et al, Impact of late diagnosis and treatment on life expectancy in people with HIV1: UK Collaborative HIV Cohort (UK CHIC) Study, BMJ Oct 2011;343:d6106
12. BHIVA guidelines for the treatment of HIV-1 positive adults with antiretroviral therapy
April 2012
13. Thompson M et al, Antiretroviral Treatment of Adult HIV Infection, JAMA
2012;308(4):387-402
14. Cohen M et al, Prevention of HIV-1 infection with early antiretroviral therapy, NEJM
2011;365(6):493-505
15. BNF September 2012, Section 5.3.1 HIV infection
16. SmPC of Ziagen® (abacavir) downloaded from www.medicines.ie on the 4th October 2012
17. SmPC of Videx® (didanosine) downloaded from www.medicines.ie on the 4th October 2012
18. SmPC of Emtriva® (emtricitibine) downloaded from www.medicines.ie on the 4th October
2012
19. SmPC of Epivir® (lamivudine) downloaded from www.medicines.ie on the 4th October
2012
20. SmPC of Zerit® (stavudine) downloaded from www.medicines.ie on the 4th October 2012
21. SmPC of Viread® (tenofovir) downloaded from www.medicines.ie on the 4th October 2012
22. SmPC of Retrovir® (zidovudine) downloaded from www.medicines.ie on the 4th October
2012
23. SmPC of Sustiva® (efavirenz) downloaded from www.medicines.ie on the 4th October 2012
24. SmPC of Intelence® (etravirine) downloaded from www.medicines.ie on the 4th October
2012
25. SmPC of Viramune ® (nevirapine) downloaded from www.medicines.ie on the 5th October
2012
26. SmPC of Edurant® (rilpivirine) downloaded from www.medicines.ie on the 5th October
2012
27. SmPC of Reyataz® (atazanavir) downloaded from www.medicines.ie on the 5th October
2012
28. SmPC of Prezista® (darunavir) downloaded from www.medicines.ie on the 5th October
2012
29. SmPC of Telzir® (fosamprenavir) downloaded from www.medicines.ie on the 5th October
2012
30. SmPC of Crixivan® (indinavir) downloaded from www.imb.ie on the 19th October 2012
31. SmPC of Kaletra® (lopinavir/ritonavir) downloaded from www.medicines.ie on the 5th
October 2012
32. SmPC of Viracept® (nelfinavir) downloaded from www.imb.ie on the 19th October 2012
33. SmPC of Norvir® (ritonavir) downloaded from www.medicines.ie on the 6th October 2012
34. SmPC of Invirase® (saquinivir) downloaded from www.medicines.ie on the 3rd October
2012
35. SmPC of Aptivus® (tipranavir) downloaded from www.medicines.ie on the 3rd October
2012
36. SmPC of Isentress® (raltegravir) downloaded from www.medicines.ie on the 3rd October
2012
37. SmPC of Celsentri® (maraviroc) downloaded from www.medicines.ie on the 3rd October
2012
38. SmPC of Fuzeon® (enfuratide) downloaded from www.medicines.ie on the 3rd October
2012
39. Basic & clinical pharmacology / edited by Bertram G. Katzung ; associate editors, Susan B.
Masters, Anthony J. Trevor, McGraw Hill Medical 2012
40. Akanbi M, Scarsi K, Taiwo B, Murphy R, Combination nucleoside/nucleotide reverse
transcriptase inhibitors for treatment of HIV infection, Expert Opinion Pharmacotherapy
2012;13(1):65-79
41. Patel N et al, Predictors of clinically significant drug-drug interactions among patients
treated with nonnucleoside reverse transcriptase inhibitors-, protease inhibitors-, and
raltegravir-based antiretroviral regimens, The Annals of Pharmacotherapy 2011;45:317-324
42. University of Liverpool, Interactions with antiretroviral drugs, www.hivdruginteractions.org on the 3rd October 2012
43. Wong W, Luk C, Kidd M, Is there a role for primary care clinicians in providing shared care
in HIV treatment? A systematic literature review, Sex Transm Infect 2012;88:125-131Role
for primary care
44. Al-Dakkak I et al, The impact of specific HIV-treatment related adverse events on
adherence to antiretroviral therapy: A systematic review and meta-analysis, AIDS Care
2012:1-15
45. Paterson DL, Swindells S, Mohr J, Brester M, Vergis EN, Squier C, Wagener MM,
Singh N.,Adherence to protease inhibitor therapy and outcomes in patients with HIV
infection. Ann Intern Med. 2000 Jul;133(1):21-30
46. Asboe D et al, British HIV Association guidelines for the routine investigation and
monitoring of adult HIV-1 infected individuals 2011, HIV Medicine 2012;13:1-44