Angiotensin converting enzyme inhibitor and HMG-CoA reductase inhibitor as adjunct treatment for persons with HIV infection: a feasibility randomized trial

Abstract

Background: Treatments that reduce inflammation and cardiovascular disease (CVD) risk among individuals with HIV infection receiving effective antiretroviral therapy (ART) are needed.

Design and methods: We conducted a 2 × 2 factorial feasibility study of lisinopril (L) (10 mg daily) vs L-placebo in combination with pravastatin (P) (20 mg daily) vs P-placebo among participants receiving ART with undetectable HIV RNA levels, a Framingham 10 year risk score (FRS) ≥ 3%, and no indication for ACE-I or statin therapy. Tolerability and adherence were evaluated. Longitudinal mixed models assessed changes in blood pressure (BP), blood lipids, and inflammatory biomarkers from baseline through months 1 and 4.

Results: Thirty-seven participants were randomized and 34 [lisinopril/pravastatin (n=9), lisinopril/P-placebo (n=8), L-placebo/pravastatin (n=9), L-placebo/P-placebo (n=8)] attended at least one follow-up visit. Participants were 97% male, 41% white, 67% were current smokers, and 65% were taking a protease inhibitor. Median age was 48 years, CD4 count 483 cells/mm(3), FRS 7.79%, total cholesterol 184 mg/dL, and LDL-C 95 mg/dL. There was no treatment difference for pravastatin vs P-placebo in total cholesterol, LDL-C, or any of the inflammatory biomarkers. Participants randomized to lisinopril vs. L-placebo had significant declines in diastolic BP (-3.3 mmHg, p=0.05), hsCRP (-0.61 µg/mL, p=0.02) and TNF-α (-0.17 pg/mL, p=0.04). Participants taking lisinopril vs L-placebo were more likely to report missed doses (88 vs 35%; p=0.001) and have adherence <90% by pill count (42 vs. 0%; p=0.02). Few participants from either group reported side effects (n=3 vs. n=1).

Conclusions: The modest BP changes and decreased adherence with lisinopril and absence of lipid differences with pravastatin suggest future studies of these drug classes should consider a run-in period to assess adherence and use a different statin. Our results also indicate that ACE-I therapy may have anti-inflammatory benefits for ART-treated persons with HIV infection and this should be further evaluated.

Trial registration: ClinicalTrials.gov NCT00982189.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Study Design Flow-Diagram.

Figure 2. Median (IQR) Levels of Blood Pressure and Biomarkers of Inflammation for Lisinopril versus L-placebo Treatment Groups.

Values are plotted at baseline and month 1 and 4 for: a) systolic blood pressure, b) diastolic blood pressure, c) hsCRP level, d) IL-6 level, e) TNF- α level, and f) the inflammatory rank score (the rank sum for hsCRP, IL-6 and TNF-α levels). Lisinopril group is in black (solid line) and L-placebo in grey (dashed line). P-values represent treatment comparisons from longitudinal models that estimate the average differences between groups over follow-up after adjusting for baseline value (see text for absolute estimates).