Initiation of antiretroviral therapy in HIV infection: a review of interstudy consistencies.

A number of clinical trials have explored the optimal dosage for antiretroviral therapy and, in various ways, the optimal time, in terms of stage of human immunodeficiency virus (HIV) disease, at which treatment should begin. Some studies have shown that treatment with zidovudine results in a delay in progression to more advanced stages of HIV disease, and that the benefits are more durable among persons who started zidovudine with higher CD4+ cell counts. Efficacy is preserved and toxicity is reduced when zidovudine is used at dosages lower than those originally recommended. The Concorde study found that administration of zidovudine to asymptomatic persons was associated with increases in CD4+ cell counts and improvement in delaying disease progression at 55 weeks, but found no correlation between time of initiation of therapy and either longer-term delay in onset of symptomatic disease or ultimate survival. The analysis of these results, however, is complicated because of premature crossover of study participants from deferred treatment to immediate treatment. The consensus of the discussants of these studies is that antiretroviral treatment should be initiated by the time the CD4+ cell count has fallen to 200-500 cells/mm3. Although recognizing that, in general, viral infections call for treatment, the panelists were divided in their opinions about treatment of asymptomatic patients with CD4+ cell counts > 500/mm3.