Angiotensin converting enzyme inhibitor and HMG-CoA reductase inhibitor as adjunct treatment for persons with HIV infection: a feasibility randomized trial.
BACKGROUND
Treatments that reduce inflammation and cardiovascular disease (CVD) risk among individuals with HIV infection receiving effective antiretroviral therapy (ART) are needed.


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.


BACKGROUND
ClinicalTrials.gov NCT00982189.
Department of Medicine, Hennepin County Medical Center (HCMC), Minneapolis, Minnesota, USA. baker459@umn.edu
Jason V
JV
Baker
Kathleen
K
Huppler Hullsiek
Rachel
R
Prosser
Daniel
D
Duprez
Richard
R
Grimm
Russell P
RP
Tracy
Frank
F
Rhame
Keith
K
Henry
James D
JD
Neaton
D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D007249:Inflammation / Q000473:pathology; D017706:Lisinopril / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D010919:Placebos; D017035:Pravastatin / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome
D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010919:Placebos; D002784:Cholesterol; D017706:Lisinopril; D017035:Pravastatin