EARLY INTERVENTION IN HIV-INFECTION - WHERE ARE WE

Data about the virology and pathogenesis of HIV disease suggest that e arly therapeutic intervention, perhaps even before the CD4+ cell count has fallen substantially, would be a theoretically sound approach. A limited number of large clinical studies address early therapy with zi dovudine. A European-Australian study, which enrolled patients with CD 4+ cell counts of greater than 400 cells/mul, found a benefit of zidov udine therapy compared to placebo in delaying minor HIV manifestations and CD4+ cell loss after a 2-year follow-up period. The results of th e Concorde study, which enrolled more than 1700 asymptomatic patients and followed them for an average of 3 years, have created controversy about the results of ACTG protocol 019, which had led to widespread zi dovudine use for patients with CD4+ cells of less than 500/mul. Althou gh there was a favorable change in CD4+ cell count in the Concorde stu dy patients assigned to immediate zidovudine treatment compared with t hose assigned to deferred treatment, there were no significant differe nces in progression to AIDS or survival. Preliminary results from foll ow-up of ACTG 019 patients enrolled with CD4+ cell counts of from 300 to 500/mul suggest that the duration of benefit of zidovudine may be l onger than in patients with CD4+ cell counts of less than 300 cells/mu l. Finally, the impact of antiretroviral therapy on quality-of-life me asures is now recognized as an important issue and should be incorpora ted into treatment decisions. The available data from several large st udies of patients with asymptomatic HIV infection are concordant, in t hat they suggest that zidovudine has a limited duration of efficacy bu t does not prolong survival. However, the benefits of zidovudine may l ast longer when this therapy is used earlier.