Protease inhibitors and cardiovascular disease: analysis of the Los Angeles County adult spectrum of disease cohort

Abstract

Since protease inhibitors (PIs) were first introduced in 1995, research has shown that use of PIs greatly improves rates of survival, while slowing HIV disease progression. However, there are concerns that use of PIs may be associated with an increased risk of cardiovascular disease (CVD). To examine the relationship between PI use and CVD among HIV-infected patients, a large retrospective/prospective observational study was conducted. The study population was a clinic-based population seeking HIV treatment services between 1990 and 2000 at several sites in Los Angeles County. CVD was defined as ischemic heart disease/coronary artery disease (ICD-9 codes 410-414, 428, and 429.7) and cerebrovascular disease/stroke (ICD-9 codes 430-438). Multiple imputation was performed on missing data, and survival analysis was performed on the imputed datasets using an extended Cox Proportional Hazards Model. The 5,667 HIV-infected individuals contributed 15,550 person-years of follow-up. Eighty incident cases of CVD were identified. Use of PIs (hazard ratio (HR)=6.22 [95% CI: 3.13–12.39], p-value <0.001) and time-dependent non-PI use (HR 3.18 [1.99–5.09], p<0.001) were associated with CVD. Clinicians should monitor treatment of HIV-infected patients for adverse CVD events, and consider alternate forms of drug therapy and CVD-preventing drugs, particularly for those with a personal or family history of CVD.

Acknowledgments

This research was also supported in part through the AIDS Interdisciplinary training grant from the National Institute of Allergy and Infectious Diseases of the NIH (T32 AI07481).

We would like to thank Drs. Barbara Visscher, William Cumberland, and Frank Sorvillo of the UCLA School of Public Health for their contributions to this study. We would also like to thank Dr. Amy Wohl and the Los Angeles County Department of Health Services HIV Epidemiology Program for use of the Los Angeles site Adult Spectrum of Disease data, which formed the basis of the research for this study (CDC surveillance grant U62/CCU806243-09).

Portions of this research were previously published in dissertation format as partial fulfilment of the requirements of a doctoral degree for the University of California, Los Angeles.