Patterns of the hazard of death after AIDS through the evolution of antiretroviral therapy: 1984-2004

Objective: To characterize changing survival patterns after development of clinical AIDS from 1984 to 2004, when different antiretroviral therapies were being introduced. Design: Cohort of homosexual men since 1984 and cohort of women since 1994. Methods: A total of 1504 men and 461 women were followed for all-cause mortality after an incident AIDS diagnosis. Relative hazards of death and relative times to death were determined in five therapy eras: no/monotherapy (July 1984-December 1989), monotherapy/combination therapy (January 1990-December 1994), HAART introduction (January 1995-June 1998), short-term stable HAART use (July 1998-June 2001), and moderate-term stable HAART use (July 2001-December 2003). Results: A total of 1057 (54%) study participants died. The time at which 25% of individuals died after an AIDS diagnosis increased significantly from 0.56 years [95% confidence interval (CI), 0.50-0.64] in the no/monotherapy era to 0.74 (95% CI, 0.67-0.82), 1.78 (95% CI, 1.29-2.44), 4.22 (95% CI, 2.94-6.05) and 5.08 years (95% CI, 2.39-10.79) in the four subsequent therapy eras, respectively. Inferences on the beneficial effects of HAART were confirmed after adjustment by age, sex, type of AIDS diagnosis and CD4 cell count at diagnosis. The pattern of the hazard of death after AIDS changed from increasing in the pre-HAART era to being lower and non-increasing in the eras of HAART. Conclusions: The sustained beneficial effect of HAART, even in individuals with clinical AIDS and extensive treatment histories, attenuates concerns about emergence of resistance but augurs that a substantial number of HIV-infected individuals may require care for very long periods.