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Roger Detels, MD, MS; Alvaro Muñoz, PhD; Glen McFarlane, MS; Lawrence A. Kingsley, DrPH; Joseph B. Margolick, MD, PhD; Janis Giorgi, PhD; Lewis K. Schrager, MD; John P. Phair, MD; for the Multicenter AIDS Cohort Study Investigators

JAMA. 1998;280:1497-1503.

Context.— Time to development of acquired immunodeficiency syndrome (AIDS) and time to death have been extended with the increased use of combination therapy and protease inhibitors. Cohort studies following up persons with human immunodeficiency virus (HIV) infection in periods characterized by different therapies offer the opportunity to estimate therapy effectiveness at the population level.

Objective.— To assess the effectiveness of self-reported, long-term potent antiretroviral therapy in a cohort of 536 men whose duration of HIV infection was known (seroconverters).

Design.— Cohort study. The cohort was compared for time to development of AIDS and time to death in 1984 to 1990, 1990 to 1993, 1993 to July 1995, and July 1995 to July 1997 when the major treatments were no therapy, monotherapy, combined therapy, and potent antiretroviral therapy, respectively. Survival analysis methods with time zero set as the date of seroconversion and incorporating staggered entries into each period were used. Mean CD4 cell change, stratified by infection duration, was determined for each period using a random effects model.

Setting.— The Multicenter AIDS Cohort Study (MACS) in 4 urban areas (Baltimore, Md; Chicago, Ill; Los Angeles, Calif; and Pittsburgh, Pa).

Participants.— A total of 5622 men who were 18 years or older were enrolled into MACS. Of the 5622, there were 2191 HIV-positive individuals 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 group of 536 who seroconverted constituted the study population.

Main Outcome Measures.— Time from seroconversion to development of AIDS and to death and change in CD4 cell count.

Results.— A total of 231 seroconverters developed AIDS, and 200 men died. Using 1990 to 1993 as the reference period, the relative hazard of AIDS was 1.04 (95% confidence interval [CI], 0.73-1.48) during 1993 to July 1995 and 0.35 (95% CI, 0.20-0.61) during July 1995 to July 1997. Relative hazards of death were 0.87 (95% CI, 0.58-1.31) and 0.62 (95% CI, 0.38-1.01) for the same periods. The relative time (the factor by which times are contracted or expanded) 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% CI, 1.07-1.36) relative 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 antiretroviral therapy was introduced, the time to development of AIDS and time to death were extended, and rate of CD4 cell count decline was arrested.

From the Schools of Public Health (Dr Detels) and Medicine (Dr Giorgi), University of California, Los Angeles; School of Hygiene and Public Health, Johns Hopkins University, Baltimore, Md (Drs Muñoz and Margolick and Mr McFarlane); Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pa (Dr Kingsley); Division of AIDS, National Institute of Allergy and Infectious Diseases, Bethesda, Md (Dr Schrager); and School of Medicine, Northwestern University, Chicago, Ill (Dr Phair).

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