How to use the newest anti-HIV drugs

Zidovudine (AZT) was approved by the FDA in 1987, didanosine (ddI) in 1991, and zalcitabine (ddC) in 1992. These drugs are nucleoside analogues directed against reverse transcriptase, and they represent the only drugs approved for HIV treatment. AZT has been used most extensively, and multiple controlled clinical trials have shown a statistically significant advantage in virtually every laboratory and clinical outcome including survival, reduction in opportunistic infections, increase in CD4 cell count, and decrease in quantitative virology. For initial therapy, ddI and ddC are less effective. A comparative clinical trial shows that they are comparably effective on the basis of clinical parameters, and use is generally reserved for patients who have taken AZT for arbitrarily defined periods and have either toxicity or progression of disease. These nucleoside analogues have time-limited benefit, meaning their effects on the immune system are temporary, presumably due to the evolution of resistance by HIV. There is considerable debate about the use of these agents, primarily because we have not developed methods to sustain the temporary benefit, so most patients eventually develop resistance and/or toxicity.