The changing pattern of AIDS-defining illnesses with the introduction of highly active antiretroviral therapy (HAART)in a London clinic

Abstract

Objectives: To quantify the progressive impact of combination antiretroviral therapy (ART) on the incidence of AIDS-defining illnesses (ADIs) over a 9-year period.

Methods: Retrospective cohort study. Eligible patients were 1538 AIDS-free, HIV-1-positive patients attending a large HIV clinic in west London who were at risk of developing AIDS because their CD4 count had declined to < or =350 x 10(6)/l cells during the period 1 January 1990 and 31 December 1998. Incidence rates for the 12 most frequent ADIs were compared for two time periods, 1990-1995 (pre-HAART) and 1996-1998 (post-HAART), using Poisson regression methods. Multivariate Poisson regression models were used to examine the contribution of ART and HAART to any observed temporal trends in incidence rates.

Results: After a median follow-up of 35 months, 450 (29%) patients had developed AIDS. Between the two time periods there was a significant decrease in the incidence of Pneumocystis carinii pneumonia (PCP) by 35% (4.11 per 100 person-years in 1990-1995 vs. 2.67 in 1996-1998;P= 0.007), Kaposi's sarcoma by 34% (3.27 vs. 2.17;P= 0.022) and cryptosporidiosis by 60% (0.76 vs. 0.31;P= 0.029). A non-significant reduction in incidence was observed for cryptococcosis by 45% (0.81 vs. 0.45;P= 0.11), oesophageal candidiasis by 29% (3.34 vs. 2.39;P= 0.053) and mycobacterium avium complex by 18% (1.58 vs. 1.29;P= 0.4), and a non-significant increase was observed for tuberculosis by 17% (0.62 vs. 0.73;P= 0.66) and non-Hodgkins lymphoma (NHL) by 51% (0.43 vs. 0.65;P= 0.31). The incidence of cerebral toxoplasmosis, cytomegalovirus, recurrent bacterial chest infections and dementia remained stable. There was a clear stepwise reduction in the incidence of PCP, Kaposi's sarcoma and cryptosporidiosis with the use of non-H AART and HAART regimens relative to no ART. In a multivariate analysis, the use of ART and HAART explained the progressive decrease in incidence of PCP and Kaposi's sarcoma.

Conclusions: The incidence of most ADIs has decreased over the last 9 years. The striking reduction in the inci-dence of PCP and Kaposi's sarcoma since 1996 can be attributed to the use of combination ART and particularly HAART. The non-significant increase in the incidence of NHL and tuberculosis needs confirmation in other patient cohorts.