Causes of the first AIDS-defining illness and subsequent survival before and after the advent of combined antiretroviral therapy

Objectives To analyse the impact of combined antiretroviral treatment (cART) on survival with AIDS, according to the nature of the first AIDS-defining clinical illness (ADI); to examine trends in AIDS-defining causes (ADC) and non-AIDS-defining causes (non-ADC) of death. Methods From the French Hospital Database on HIV, we studied trends in the nature of the first ADI and subsequent survival in France during three calendar periods: the pre-cART period (1993-1995; 8027 patients), the early cART period (1998-2000; 3504 patients) and the late cART period (2001-2003; 2936 patients). Results The three most frequent initial ADIs were Pneumocystis carinii (jirovecii) pneumonia (PCP) (15.6%), oesophageal candidiasis (14.3%) and Kaposi's sarcoma (13.9%) in the pre-cART period. In the late cART period, the most frequent ADIs were tuberculosis (22.7%), PCP (19.1%) and oesophageal candidiasis (16.2%). The risk of death after a first ADI fell significantly after the arrival of cART. Lower declines were observed for progressive multifocal leukoencephalopathy, lymphoma and Mycobacterium avium complex infection. After an ADI, the 3-year risk of death from an ADC fell fivefold between the pre-cART and late cART periods (39% vs. 8%), and fell twofold for non-ADCs (17% vs. 9%). Conclusions The relative frequencies of initial ADI have changed since the advent of cART. Tuberculosis is now the most frequent initial ADI in France; this is probably the result of the increasing proportion of migrants from sub-Saharan Africa. After a first ADI, cART has a major impact on ADCs and a smaller impact on deaths from other causes. The risk of death from AIDS and from other causes is now similar.