Background:  Lipid abnormalities and cardiovascular disease (CVD) in HIV-infected patients have led to concerns about the contribution of ART agents to these co-morbidities.

Methods:  We analyzed a prospective, dynamic cohort of >7800 patients followed since 1993 in the HIV Outpatient Study (HOPS). We used c² and logistic regression analyses to assess risk factors for cardiovascular events (myocardial infarction [MI], peripheral vascular disease, coronary artery disease, and stroke), including time on HAART after its initiation (took HAART ³95% vs. <95% of the time). We also assessed the reduction in risk for CVD associated with treatment of hypertension or hyperlipidemia.

Results:  We examined 1744 patients contributing data to HOPS from 1989 to June 30 2005, of whom 48 (2.8%) had a CVD diagnosis in that period, and 538 (31%) had 8 years of follow-up. MI cases peaked from 2000 to 2002 and have been decreasing in frequency in subsequent years coincident with increased use of medications for hypertension and hyperlipidemia. Univariate analysis demonstrated a trend toward a decreased risk of CVD in patients who remained on HAART ³95% of the time over an 8-year period (c² test for trend, p = 0.056). In the multivariate analysis, significant (p <0.05) independent risk factors for CVD were (adjusted odds ratio shown in parentheses):  hypertension (2.2), HDL <30 mg/dL (2.6), diabetes mellitus (2.4), and age >40 years (3.3). Pre-HAART CD4 count, percentage of time on HAART, specific ART agents, and ART switches to other drugs or classes were not statistically associated with CVD. Use of anti-hypertensive medications was associated with lower risk for CVD among hypertensive (n = 971) patients (HR = 0.07, p <0.001), and use of lipid-lowering agents was associated with reduced risk for CVD among hyperlipemic (n = 595) patients (HR = 0.08, p <0.001). Within a subset of patients who had data on triglycerides (n = 435), cholesterol (n = 460), LDL (n = 406), and HDL (n = 422) over the 8-year period, changes in total cholesterol, LDL, HDL, and triglycerides were all more favorable in the ≥95% vs <95% groups (total cholesterol:  3.6 vs 8.5 mg/dL; LDL –3.4 vs 1.9 mg/dL; HDL 1.0 vs 1.2 mg/dL; triglycerides 13.7 vs 48.6 mg/dL, respectively).

Conclusions:  In the HOPS, risk of CVD was associated with traditional CVD risk factors, reduced by use of antihypertensive and lipid-lowering agents, and was unrelated to changes in ART.