ObjectiveTo characterize the relationships among highly active antiretroviral therapy (HAART), HIV-1 RNA levels, immune system markers, and clinical outcome in a cohort of HIV-1–infected homosexual men.PatientsA total of 123 men enrolled in the Amsterdam cohort study of HIV-1 infection and AIDS with a documented seroconversion for HIV-1 antibodies and known date of seroconversion were included in this study.MethodsCD4+/CD8+T-cell counts and HIV-1 RNA levels in plasma were measured approximately every 6 months. Dates of starting and stopping antiretroviral therapy were also recorded. The relationship between HIV-1 RNA in plasma, CD4+/CD8+T-cell counts and HAART and their influence on clinical outcome were examined using a graphical chain modeling approach. Generalized estimating equations were used to examine correlations among the three disease markers. Hazards models with time-dependent covariates were used to examine the influence of HAART and the disease markers on progression to AIDS.ResultsHAART was significantly associated with reduced disease progression (relative hazard [RH] of AIDS, 0.20;, 95% confidence interval [CI], 0.05–0.85). The most recent HIV-1 RNA measurement and CD4+T-cell count are independently associated with disease progression (adjusted RH for HIV-1 RNA 1.8 per log10increase; 95% CI, 1.2–2.6,p= .002; adjusted RH for CD4+0.48 per 100 × 106/L increase; 95% CI, 0.40–0.58;p<.001). Depending on these measurements, HAART was no longer significantly associated with AIDS (adjusted RH, 0.81; 95% CI, 0.18–3.6;p= .78).ConclusionsHIV-1 RNA levels in plasma and CD4+T-cell counts are currently considered as effective surrogate markers for the effect of HAART on disease progression in this cohort.