Surrogate markers for disease progression in treated HIV infection

Objective: To characterize the relationships among highly active antiretrov iral 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 me asured approximately every 6 months. Dates of starting and stopping antiret roviral therapy were also recorded. The relationship between HIV-1 RNA in p lasma, CD4(+)/CD8(+) T-cell counts and HAART and their influence on clinica l outcome were examined using a graphical chain modeling approach. Generali zed 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 A IDS. Results: HAART was significantly associated with reduced disease progressio n (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). Depen ding on these measurements, HAART was no longer significantly associated wi th 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 curren tly considered as effective surrogate markers for the effect of HAART on di sease progression in this cohort.