[HIV infection--current possibilities in antiviral therapy]

Abstract

Three drugs are currently available to treat HIV infection: zidovudine, didanosine, and zalcitabine. They resemble the natural nucleosides and inhibit retrotranscriptase, an enzyme which transforms HIV's genomic RNA into DNA. Indications for treatment are symptomatic HIV infection and, in asymptomatic patients, moderate immunodeficiency with a CD4-lymphocyte count below 350/mm3. In patients who have not yet received antiviral treatment, zidovudine remains the drug of choice, in spite of its toxicity for the bone marrow, which is particularly problematic in those with advanced immunodeficiency. Unfortunately, HIV develops resistance to zidovudine, and its efficacy wanes after a few months. When that happens, zidovudine may be replaced by didanosine, which is mainly toxic for the pancreas, or by zalcitabine, which causes peripheral neuropathy. A number of drugs are being developed. Among these, nonnucleoside retrotranscriptase inhibitors are well tolerated, but rapid development of resistance is problematic. Resistance seems less of a problem for inhibitors of the viral protease, but biodispensibility of these drugs is poor.