Chemoprophylaxis in HIV

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.

• Early disease (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 features pneumocystis carinii pneumonia (PCP), tuberculosis, atypical mycoplasma, candidiasis, cytomegalovirus and toxoplasma. Recent years have seen TB overtake PCP as the commonest indicator disease. Globally, the important infections are tuberculosis, pneumococcal pneumonia, shingles, malaria, staphylococcal skin infections, septicaemia.
• Late disease (WHO stage 4 - equivalent to AIDS). Common recurring infections are pneumocystis, cryptococcus, toxoplasma, TB.

Highly active anti-retroviral therapy (HAART)^1,4,5

• Anti-retroviral 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.⁶
• 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 being considered in resource-poor areas where physicians and clinical services are few.⁷

Prevention of HIV-related opportunistic infections^1,8,9

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

• Tuberculosis - 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 world.
  • In South Africa (TB commonest opportunistic infection, most patients will have positive skin test) isoniazid given where the CD4 count is equal to or less than 300/mm³.
  • In USA, isoniazid only given if the skin test positive.
  • UK has adopted WHO Policy - ask all HIV positive patients about symptoms suggestive of TB, treat those with a positive skin test.
• Pneumocystis carinii - 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 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 UK.
• Microsporidiosis, cryptosporidiosis - there is no known prophylaxis available.

• Cytomegalovirus - 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 candidosis - 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, sulphadiazine 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.