Factors influencing survival after AIDS: Report from the multicenter AIDS cohort study (MACS)

Multicenter AIDS Cohort Study The objective of this study was to determine if clinical signs, symptoms, laboratory variables, and use of therapeutic or prophylactic agents have prognostic associations with survival after diagnosis of clinical AIDS. A total of 2,168 homosexual men, seropositive for human immunodeficiency virus type 1 (HIV-1) participated in a longitudinal cohort study of the greater metropolitan areas of Baltimore, Maryland, Washington, D.C., Chicago, Illinois, Pittsburgh, Pennsylvania, and Los Angeles, California, U.S.A.—the Multicenter AIDS Cohort Study (MACS). Variables within 6 months prior to AIDS diagnosis included age, CD4⁺ lymphocyte counts, hemoglobin, and selfreported thrush, fever, anti-retroviral therapy (ART) beginning prior to AIDS onset, and ART beginning after AIDS (as a time-dependent covariate) were analyzed as mutually exclusive categories, as was prophylaxis for Pneumocystis carinii pneumonia (PCP). Univariate and multivariate survival models of time from AIDS to death were fit. In univariate analysis, younger age, higher counts of CD4⁺ lymphocytes, hemoglobin, and absence of thrush or fever prior to AIDS onset were associated with longer survival after AIDS. Those who began ART within 3 months after AIDS onset had longer median survival (1.75 years), from 3 months after AIDS, when compared with those who began ART prior to AIDS (1.18 years). This comparison is not influenced by the bias that those who survive longer have a greater likelihood to subsequently receive ART. Prophylaxis for PCP beginning after AIDS onset was also associated with longer post-AIDS survival when compared with beginning prophylaxis prior to AIDS or never using prophylaxis. In multivariate analysis, age <37 years at AIDS onset, higher hemoglobin level, and higher CD4⁺ lymphocyte count remained prognostically beneficial for survival after AIDS (relative hazards 0.78, 0.91 per g/dL and 0.80 per 100 cells × 10⁶/L, respectively). When PCP prophylaxis and ART were started only after AIDS onset (considered as time-dependent covariates, they reduced the hazard of death by 40% and 50%, respectively. The hazard of death after AIDS was 26% lower in those using ART prior to AIDS than in those never using ART (p = 0.095). Clinical variables such as younger age, higher hemoglobin level, and higher CD4⁺count are prognostically beneficial for survival after AIDS. Pre-AIDS ART and pneumocystis prophylaxis are presently the standard of care in treating those with HIV-1 infection and have been shown to delay the onset of AIDS. Survival after AIDS onset was longer for men who received pre-AIDS ART compared with those who never received ART, but it was shorter in the former group than in those initiating ART after AIDS. This finding suggests a transient beneficial effect from ART that is not completely attenuated at AIDS in the pre-AIDS ART recipient.