Early Intervention in HIV Infection

Abstract

Data about the virology and pathogenesis of HIV disease suggest that early 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 zidovudine. A European-Australian study, which enrolled patients with CD4⁺ cell counts of greater than 400 cells/μl, found a benefit of zidovudine therapy compared to placebo in delaying minor HIV manifestations and CD4⁺ cell loss after a 2-year follow-up period. The results of the 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 zidovudine use for patients with CD4⁺ cells of less than 500/μl. Although there was a favorable change in CD4⁺ cell count in the Concorde study patients assigned to immediate zidovudine treatment compared with those assigned to deferred treatment, there were no significant differences in progression to AIDS or survival. Preliminary results from follow-up of ACTG 019 patients enrolled with CD4⁺ cell counts of from 300 to 500/μl suggest that the duration of benefit of zidovudine may be longer than in patients with CD4⁺ cell counts of less than 300 cells/μl. Finally, the impact of antiretroviral therapy on quality-of-life measures is now recognized as an important issue and should be incorporated into treatment decisions. The available data from several large studies of patients with asymptomatic HIV infection are concordant, in that they suggest that zidovudine has a limited duration of efficacy but does not prolong survival. However, the benefits of zidovudine may last longer when this therapy is used earlier.