Surrogate markers for disease progression in treated HIV infection

Objective: To 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. Patients: A 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. Methods: CD4(+)/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. Results: HAART was significantly associated with reduced disease progression (relative hazard [RH] of AIDS, 0.20;, 95% confidence interval [Cl], 0.05-0.85). The most recent HIV-1 RNA measurement and CD4(+)/CD8(+) T-cell count are independently associated with disease progression (adjusted RH for HIV-1 RNA 1.8 per log(10) increase; 95% CI, 1.2-2.6, p = .002 adjusted RH for CD4(+) 0.48 per 100 x 10(6)/L increase; 95% Cl, 0.40-0.58; p < .001). Depending on these measurements, HAART was no longer significantly associated with AIDS (adjusted RH, 0.81; 95% Cl, 0.18-3.6; p = .78). Conclusions: HIV-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.