Abstract

AIDS: Results of ACTG 175 and Delta, large multicenter studies comparing combinations of nucleoside antiretroviral drugs with monotherapy, are reported. ACTG 175 enrolled 2,500 HIV-infected patients (1,000 subjects were AZT naive) over a 3-year period and randomized them to one of four drug regimens: AZT plus ddC, AZT plus ddI, AZT alone, or ddI alone. In moderately immunocompromised patients, the best results are obtained with either combination, or with ddI alone. In patients already on AZT, it is better to add or switch to ddI than to continue AZT monotherapy. The Delta trial enrolled 3,300 subjects and studied the same combinations as in ACTG 175 and AZT monotherapy, but did not study ddI monotherapy. Patients receiving combination therapy did better than those receiving AZT alone. AZT-experienced patients, regardless of the treatment received, experienced similar rates of progression to AIDS or death. This study was ceased prematurely due to the high rate of deaths in AZT-naive subjects receiving AZT alone compared to combination therapies. Other drug combination studies, such as AZT combined with 3TC, show superiority to AZT monotherapy in decreasing viral load and increasing CD4 counts, but do not correlate the results with clinical benefit. Other issues discussed include development and use of non-nucleoside reverse transcriptase inhibitors, studies involving HIV protease inhibitors, and the development of resistance and cross-resistance to various classes of antiviral agents.