EFFECTIVENESS OF POTENT ANTIRETROVIRAL THERAPY ON TIME TO AIDS AND DEATH IN MEN WITH KNOWN HIV-INFECTION DURATION

Context.-Time to development of acquired immunodeficiency syndrome (AI DS) and time to death have been extended with the increased use of com bination therapy and protease inhibitors. Cohort studies following up persons with human immunodeficiency virus (HIV) infection in periods c haracterized by different therapies offer the opportunity to estimate therapy effectiveness at the population level. Objective.-To assess th e effectiveness of self-reported, long-term potent antiretroviral ther apy in a cohort of 536 men whose duration of HIV infection was known ( seroconverters). Design.-Cohort study. The cohort was compared for tim e to development of AIDS and time to death in 1984 to 1990, 1990 to 19 93, 1993 to July 1995, and July 1995 to July 1997 when the major treat ments were no therapy, monotherapy, combined therapy, and potent antir etroviral therapy, respectively. Survival analysis methods with time z ero set as the date of seroconversion and incorporating staggered entr ies into each period were used. Mean CD4 cell change, stratified by in fection duration, was determined for each period using a random effect s model. Setting.-The Multicenter AIDS Cohort Study (MACS) in 4 urban areas (Baltimore, Md; Chicago, III; Los Angeles, Calif; and Pittsburgh , Pa). Participants.-A total of 5622 men who were 18 years or older we re enrolled into MACS. Of the 5622, there were 2191 HIV-positive indiv iduals at enrollment. Of the 3431 men who were HIV-negative, 536 were observed to seroconvert and were followed up for up to 13 years. The g roup of 536 who seroconverted constituted the study population. Main O utcome Measures.-Time from seroconversion to development of AIDS and t o death and change in CD4 cell count. Results.-A total of 231 seroconv erters developed AIDS, and 200 men died. Using 1990 to 1993 as the ref erence period, the relative hazard of AIDS was 1.04 (95% confidence in terval [GI], 0.73-1.48) during 1993 to July 1995 and 0.35 (95% CI, 0.2 0-0.61) during July 1995 to July 1997. Relative hazards of death were 0.87 (95% CI, 0.58-1.31) and 0.62 (95% Cl, 0.38-1.01) for the same per iods. The relative time (the factor by which times are contracted or e xpanded) to development of AIDS was 0.97 (95% CI, 0.86-1.09) for 1993 to July 1995 and 1.63 (95% CI, 1.40-1.89) for July 1995 to July 1997. Relative survival time for 1993 to July 1995 was 1.01 (95% CI, 0.91-1. 12) and for July 1995 to July 1997 was 1.21 (95% Cl, 1.07-1.36) relati ve to 1990 to 1993. The rate of CD4 cell count decline in July 1995 to July 1997 was significantly lower (P<.05) compared with the previous 2 periods. Conclusions.-In the calendar period when potent antiretrovi ral therapy was introduced, the time to development of AIDS and time t o death were extended, and rate of CD4 cell count decline was arrested .