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Chemoprophylaxis in HIV

This PatientPlus article is written for healthcare professionals so the language may be more technical than the condition leaflets. You may find the abbreviations list helpful.

Chemoprophylaxis is used to prevent infection in HIV-positive patients.1,2,3,4

  • Primary chemoprophylaxis is used when the CD4 lymphocyte count drops below a certain level, making opportunistic infection likely.
  • Secondary chemoprophylaxis is used to prevent the recurrence of an infection that has already occurred.

Primary prevention

  • Early disease (World Health Organization (WHO) stages 1-3). The type of infection will depend on local disease prevalence. Some idea of UK prevalence can be obtained from statistics of diseases which indicate possible development of AIDS (so-called 'indicator diseases'). UK data commonly feature pneumocystis pneumonia (PCP), tuberculosis (TB), atypical mycoplasma, candidiasis, cytomegalovirus (CMV) and toxoplasma. Recent years have seen TB overtake PCP as the most common indicator disease. Globally, the important infections are TB, pneumococcal pneumonia, shingles, malaria, staphylococcal skin infections, and septicaemia. Of these, TB is the most prevalent and WHO is pursuing joint prevention/treatment interventions, providing care in homes, communities and hospitals.5
  • Late disease (WHO stage 4 - equivalent to AIDS). Common recurring infections are pneumocystis, cryptococcus, toxoplasma, and TB.

Highly active antiretroviral therapy (HAART)1,4,6

  • Antiretroviral drugs are now available to inhibit the replication of the human immunodeficiency virus. This helps to prolong life, restore the patient's immune system to something approaching normal activity, and reduces the chances of opportunistic infection developing. Combinations of three or more drugs are given to lessen the possibility of resistance.
  • There are four main groups:
    • Nucleoside/nucleotide reverse transcriptase inhibitors - e.g. zidovudine
    • Non-nucleoside reverse transcriptase inhibitors - e.g. efavirenz
    • Protease Inhibitors - e.g. atazanavir
    • Fusion or entry inhibitors - e.g. enfuvirtide
  • New classes and new combinations are being developed all the time. Sequencing the drugs so that the one with the least cross-resistance is used first, seems to be the most effective approach.7
  • There is a growing body of evidence to suggest that HAART may obviate the need to remain on chemoprophylaxis lifelong, providing the CD count remains high. It is , however, still necessary for patients who do not sustain immune recovery.
  • HAART should be differentiated from post-exposure prophylaxis (PEP). In this, a 28 day regime of drugs is given to prevent infection in non-HIV individuals after suspected exposure - e.g. healthcare workers who have been in a situation in which exposure is possible. It should be given as soon as possible, and certainly within 72 hours.

Expansion of HAART into the community is important in resource-poor areas where physicians and clinical services are few.8 Prevention of transmission from mother to child is of particular significance.9

Prevention of HIV-related opportunistic infections1,10,11

Where there is no prevalent UK policy, the WHO or US policy is adopted.

  • TB - this is 30-50 times more likely to develop in HIV-positive patients than in those who do not have the virus. Primary chemoprophylaxis strategy differs according to prevalence around the world:
    • In South Africa (TB is the most common opportunistic infection, and most patients will have a positive skin test) isoniazid is given where the CD4 count is equal to or less than 300/mm3.
    • In the USA, isoniazid only is given if the skin test is positive.
    • The UK has adopted WHO policy - ask all HIV-positive patients about symptoms suggestive of TB; treat those with a positive skin test.
  • Pneumocystis jirovecii (carinii) pneumonia - US policy is to offer co-trimoxazole to all patients with a CD count below 200/mm3, or who have an unexplained fever for more than two weeks, or a history of oral candidiasis. Discontinue if CD count remains above 200/mm3 for 3-6 months.
  • Bacterial pneumonia - offer pneumococcal vaccine to all patients with CD count above 200/mm3 who have not had vaccine within five years.
  • Oral candidiasis - prophylaxis is not usually given in the UK.
  • Mycobacterium avian intracellulare (MIA) - no consistent policy in the UK. Some clinics offer azithromycin or clarithromycin if CD count falls below 50/mm3.
  • Toxoplasma - offer co-trimoxazole for toxoplasma-positive patients with counts below 100/mm3 or test at regular intervals.
  • Varicella zoster - if susceptible (no history of chickenpox, shingles, or detectable antibody) - offer varicella immune globulin within 96 hours of exposure.
  • CMV and herpes simplex - primary prophylaxis is not routinely offered in the UK.
  • Microsporidiosis, cryptosporidiosis - there is no known prophylaxis available.
  • Vaccines are routinely offered in the UK against swine flu and influenza to all patients living with HIV. Individuals especially at risk are those with a CD count below 200.12

Secondary prevention1

  • Cytomegalovirus (CMV) - use ganciclovir to prevent retinitis. Long-acting drug-release intravitreous implants have been shown to be cost-effective.
  • Herpes simplex - may require temporary daily suppressive treatment with oral aciclovir, famciclovir, or valaciclovir.
  • Oral candidiasis - may require suppressive treatment with an antifungal.
  • Salmonella - long-term therapy may be required to prevent septicaemia - ciprofloxacin is the first choice.
  • Toxoplasma - give pyrimethamine, sulfadiazine and leucovorin to prevent relapse, discontinue if the CD4 cell count increases above 200 and is sustained for at least six months. Resume if the count subsequently falls below 200.

Document references

  1. CDC; Centers for Disease Control and Prevention. Guidelines for Preventing Opportunistic Infections Among HIV-Infected Persons (2002); US-Based.
  2. World Health Organization; Guidelines on co-trimoxazole prophylaxis for HIV-related infections among children, adolescents and adults (2006); Recommendations for a public health approach.
  3. What is HIV antiretroviral treatment? Avert.org - formerly AIDS Education and Research Trust.
  4. Multidrug resistant HIV and rapid progression of disease: a single case in New York, Health Protection Agency, CDR Weekly; 2005; 15 (8)
  5. WHO; Joint HIV/AIDS Interventions 2010.
  6. Yeni P; Update on HAART in HIV. J Hepatol. 2006;44(1 Suppl):S100-3. Epub 2005 Nov 28. [abstract]
  7. Martinez-Cajas JL, Wainberg MA; Antiretroviral therapy : optimal sequencing of therapy to avoid resistance. Drugs. 2008;68(1):43-72. [abstract]
  8. Mermin J, Were W, Ekwaru JP, et al; Mortality in HIV-infected Ugandan adults receiving antiretroviral treatment and survival of their HIV-uninfected children: a prospective cohort study. Lancet. 2008 Mar 1;371(9614):752-9. [abstract]
  9. Ndirangu J, Newell ML, Tanser F, et al; Decline in early life mortality in a high HIV prevalence rural area of South AIDS. 2010 Jan 11. [abstract]
  10. WHO; Interim Policy on Collaborative TB/HIV Activities. World Health Organization. 2004.
  11. TB HIV Update; World Health Organization July 2006.
  12. Swine Flu; Terrence Higgins Trust 2009.

Internet and further reading

  • Smith S; Pre-exposure chemoprophylaxis for HIV - It is time. Retrovirology 2004;1:16.

Acknowledgements

EMIS is grateful to Dr Laurence Knott for writing this article. The final copy has passed scrutiny by the independent Mentor GP reviewing team. ©EMIS 2010.
Document ID: 300
Document Version: 3
Document Reference: bgp25062
Last Updated: 8 Mar 2010
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