Background:  Many studies have reported the dramatic decline in the risk of death since the introduction of potent combined ART (cART), but only a few have evaluated whether the risk reduction was similar for each specific initial AIDS-defining illness and for AIDS-defining and non-AIDS defining causes of death.

Methods:  From the French Hospital Database on HIV, we studied the survival after the first AIDS-defining illness in 3 calendar periods:  pre-cART period (1993-1995), early cART period (1998-2000), and late cART period (2001-2003). Hazards of deaths among the 3 periods were estimated by Cox models adjusting for age, CD4, transmission group, and initiation of a mono, dual, or cART therapy, as well as used of prophylaxis. Death from all causes, AIDS-defining and non-AIDS-defining, were considered as specific endpoints. Risk of deaths accounting for competing risks were estimated at 3 years.

Results:  A total of 8027 patients presented an initial AIDS-defining illness in the pre-cART period (29,986 person-years), 3504 (14,095 person-years), and 2936 (6601 person-years), respectively, in the early and late cART periods. In the pre-cART period, the 3 most frequent initial AIDS-defining illness were Pneumocystis carinii pneumonitis (PCP) (15.6%), esophageal candidiasis (14.3%), and Kaposi’s sarcoma (13.9%). It was tuberculosis (22.7%), PCP (19.1%), and esophageal candidiasis (16.2%) in the late cART period. Hazard of death was significantly reduced in the cART period as compared with the pre-cART period (HR = 0.27, 95%CI 0.24 to 0.30). Maximal decline was observed after a diagnosis of Kaposi sarcoma (85%), cytomegalovirus (CMV) (83%), PCP (81%), whereas minimal decline was observed after progressive multifocal leukoencephalopathy (PML) (54%), lymphoma (58%), Mycobacterium avium complex (MAC) (58%). Between the 2 cART periods, hazard of death was still decreasing globally (HR = 0.87, 95%CI 0.77 to 0.98) though statistical significance was not reached for any specific AIDS-defining illness. The risk of death from an AIDS-defining cause following an AIDS diagnosis was 5-fold reduced between the pre-cART period and the late cART periods (39% vs 8%) whereas the risk of death from a non-AIDS-defining cause was only 2-fold reduced (17% vs 9%).

Conclusions:  The pattern of presentation of the initial AIDS-defining illness has changed over time. Tuberculosis is now the most frequent presenting AIDS-defining illness in France. A lengthening of survival concerned all the AIDS-defining illnesses, although it was more pronounced for some diseases than for others. Benefit of cART was large on AIDS-defining causes of death, but also concerned non-AIDS-defining causes to a smaller extent. In the cART period, the absolute risk of death from AIDS-defining causes and non-AIDS-defining causes cause of deaths are now similar.