General Principles

• No current antiviral agents or combinations eliminate HIV infection, but the most effective combinations (so-called highly-active anti-retroviral therapy, HAART) produce profound suppression of viral replication in many patients which results in useful reconstitution of the immune system. This can be measured by a fall in the plasma viral load and an increase in the numbers of cytotoxic T-cells (CD4 count) in patients' plasma. Rates of opportunistic infections such as Pneumocystis carinii pneumonia and CMV retinitis are reduced in patients with restored CD4 counts and their life-expectancy is markedly increased. Efficacy of viral suppression, however, must be balanced against the risks of unwanted effects from the multiple drugs used. Combination therapy reduces the risks of emergence of resistance to antiretroviral drugs, which is increasing in incidence even in patients newly-diagnosed with HIV.

• HAART comprises two nucleoside reverse transcriptase inhibitors used with either a non-nucleoside reverse transcriptase inhibitor or one or two protease inhibitors.

• The decision to begin antiretroviral therapy is based on the CD4 cell count, the plasma viral load and the intensity of the patient's clinical symptoms. Therapy is switched to alternative combinations if these variables deteriorate. Available information about drugs and combinations is accumulating monthly and the choice of agents is best made after reference to contemporary expert advice.

• Pregnancy and breast-feeding pose especial problems; therapy at this time is aimed to minimise toxicity to the fetus while reducing maternal viral load and the catastrophic results of HIV transmission to the neonate. Prevention of maternal-fetal and maternal-infant transmission is the most cost-effective way of using antiretroviral drugs in less developed countries.

• Combination antiretroviral therapy is associated with redistribution of body fat in some patients ('lipodystrophy syndrome'), and protease inhibitors may disturb lipid and glucose metabolism. Appropriate laboratory tests to monitor these effects should be performed.

• Impaired cell-mediated immunity leaves the host prey to many (opportunistic) infections including: candidiasis, coccidioidomycosis, cryptosporidiosis, cytomegalovirus disease, herpes simplex, histoplasmosis, Pneumocystis carinii pneumonia, toxoplasmosis and tuberculosis (with multiply-resistant organisms). Treatment of these conditions is referred to elsewhere in this text; for a comprehensive review of the antimicrobial prophylaxis of opportunistic infections in patients with HIV infection, readers are referred to Kovacs & Masur 2000 New England Journal of Medicine 342:1416.

Antiretroviral drugs may also be used in combination to reduce the risks of acquisition of HIV from accidental needlestick injuries from HIV-contaminated sharps such as needles. The decision to offer this postexposure prophylaxis (PEP), and the optimal combination of drugs used, should be made by experts and administration must begin rapidly (within a few hours of the injury).

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