Traditional and HIV-Specific Risk Factors for Cardiovascular Morbidity and Mortality Among HIV-Infected Adults in Brazil

Background: Cardiovascular disease (CVD) is a leading cause of morbidity and mortality in HIV-infected (HIV+) persons. While relationships between antiretroviral therapy (ART) and CVD remain unclear, agents possibly associated with increased CVD risk are commonly used in low- and middle-income countries. We assessed risk factors for CVD-related morbidity and mortality in a cohort of HIV+, ART-treated adults from Rio de Janeiro, Brazil.

Methods: Hospital records and mortality data were examined for incident CVD events among HIV+ persons ≥18 years of age who were on ART between 2000-2010. Poisson regression models initially adjusted for age, sex, race, nadir CD4+ T-cell count, HIV-1 RNA, time on ART, traditional CVD risk factors and year of cohort entry, followed by the addition of individual ART agents.

Results: Of 2,960 eligible persons, 109 had a CVD event (89 hospitalizations, 20 deaths). Participants were 69% male, 47% white, and had a median age of 42 years and time on ART 4.6 years. Age ≥40, non-white race, nadir CD4+ T-cell count ≤50 cells/mm³, detectable HIV-1 RNA prior to the event, less time on ART and a history of hypertension and CVD were significantly associated with CVD event incidence (p<0.05, Fig. 1). Cumulative tenofovir, zidovudine, efavirenz and ritonavir-boosted atazanavir, darunavir and lopinavir use were associated with decreased CVD event risk, with the strongest effects observed with tenofovir and boosted atazanavir (Fig. 2A). Recent tenofovir and boosted atazanavir use were also associated with decreased risk, while recent stavudine, nevirapine and unboosted nelfinavir and indinavir were associated with increased CVD event risk (Fig. 2B). Cumulative lamivudine use was associated with decreased risk, although use was pervasive (97%). Neither cumulative nor recent abacavir use influenced CVD event risk, though use was low in this setting (7%).

Conclusion: Both recent and cumulative tenofovir and ritonavir-boosted atazanavir exposure were associated with reduced CVD event risk while other commonly used agents were associated with increased risk. These are the first data describing CVD event risk and ART exposure in Latin America, and may inform international guidelines for universal ART access in resource-limited settings.