HAART on Incident Cancer and Noncancer AIDS Events Among Male HIV
Objective: To explore the impact of highly active antiretroviral therapy (HAART) on the prevention of AIDS-defining cancers relative to other AIDS-defining events.
Design: Prospective cohort study using 2121 HIV+ male seroconverters (median age: 28 years, 51% white/non-Hispanic) in the Tri-Service AIDS Clinical Consortium (n = 1694) and the Multicenter AIDS Cohort Study (n = 427).
Methods: Poisson regression models, with calendar periods to represent antiretroviral therapy, were extended to analyze first incident AIDS-defining cancers and other first AIDS-defining events as competing risks.
Results: Eighty-one AIDS-defining cancers (64 Kaposi sarcomas; 17 non-Hodgkin lymphomas) and 343 other AIDS events occurred during 14,483 person-years in 1990-2006. The rate ratio of AIDS-defining cancers during the HAART calendar period was 0.26 (95% confidence limits: 0.15, 0.46) and of other AIDS-defining events was 0.28 (95% confidence limits: 0.21, 0.36) compared with the monotherapy/combination therapy calendar period, adjusting for age, infection duration, race, and cohort. The association of HAART with decreased AIDS incidence seemed to be equal (interaction ratio = 0.95 (95% confidence limits: 0.51, 1.74) for AIDS-defining cancers and other AIDS-defining events.
Conclusions: In human immunodeficiency virus-infected men, HAART seems equally protective against first AIDS-defining cancers and other first AIDS-defining events.

The protective effect of highly active antiretroviral therapy (HAART) on the incidence of AIDS or death has been well established via randomized trials and observational studies. Previous research has focused primarily on the effect of HAART on incident AIDS, although HAART has also been shown to reduce the incidence of specific AIDS-defining events, namely, AIDS-defining cancers, opportunistic infections, and recurrent AIDS events. However, it is unclear whether the protective effect of HAART on prevention of AIDS is as potent for AIDS-defining cancers as other AIDS-defining events.

Among men, AIDS-defining cancers include Kaposi sarcoma (KS) and non-Hodgkin lymphoma (NHL), specifically Burkitt, immunoblastic, and central nervous system lymphomas. Among those with AIDS in the United States, the incidence rates of KS and NHL were 1150 and 760 events per 100,000 person-years between 1990 and 2002. Several studies have compared the incidence of KS and NHL among those who have and have not been treated with HAART, measured directly by HAART use and indirectly by calendar period as an instrumental variable for HAART use. The majority of observational studies suggest that HAART provides strong protection against KS and NHL. However, 2 studies reported an increase in the incidence of NHL in the HAART calendar period. HAART may also be less effective at delaying mortality among those with AIDS-defining cancers than for other AIDS-defining events. Despite the totality of evidence supporting a protective effect of HAART on the incidence of KS and NHL, it remains unclear whether HAART is as effective at reducing the incidence of AIDS-defining cancers as it is for other AIDS-defining events. Refined estimates of the association of HAART with AIDS-defining cancers are critical to understanding the treated history of HIV infection. Efforts to alter the constituents of HAART may be required if heterogeneities between AIDS-defining cancers and other AIDS-defining events are uncovered.

We used calendar period as an instrumental variable for HAART exposure and applied statistical methods to estimate the effect of HAART on AIDS-defining cancers relative to the effect of HAART on non-cancer AIDS-defining illnesses using the Tri-Service AIDS Clinical Consortium (TACC) and Multicenter AIDS Cohort Study (MACS) observational data. We hypothesized that the protective effect of HAART on AIDS-defining cancers would be less than the effect of HAART on non-cancer AIDS-defining illnesses.