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Cardiovascular outcomes among HIV-infected veterans receiving atazanavir

LaFleur, Joannea,b; Bress, Adam P.b,c; Rosenblatt, Lisad; Crook, Jacobb,e; Sax, Paul E.f; Myers, Joeld; Ritchings, Coreyd

doi: 10.1097/QAD.0000000000001594
Clinical Science

Objective: Patients with HIV infection have an increased risk of cardiovascular disease compared with uninfected individuals. Antiretroviral therapy with atazanavir (ATV) delays progression of atherosclerosis markers; whether this reduces cardiovascular disease event risk compared with other antiretroviral regimens is currently unknown.

Design: Population-based, noninterventional, historical cohort study conducted from 1 July 2003 through 31 December 2015.

Setting: Veterans Health Administration hospitals and clinics throughout the United States.

Participants: Treatment-naive patients with HIV infection (N = 9500).

Antiretroviral exposures: Initiating antiretroviral regimens containing ATV, other protease inhibitors, nonnucleoside reverse transcriptase inhibitors (NNRTIs), or integrase strand transfer inhibitors (INSTIs).

Main outcome/effect size measures: Incidence rates of myocardial infarction (MI), stroke, and all-cause mortality within each regimen. ATV versus other protease inhibitor, NNRTI, or INSTI covariate-adjusted hazard ratios by using Cox proportional hazards models and inverse probability of treatment weighting.

Results: Incidence rates for MI, stroke, and all-cause mortality with ATV-containing regimens (5.2, 10.4, and 16.0 per 1000 patient-years, respectively) were lower than with regimens containing other protease inhibitors (10.2, 21.9, and 23.3 per 1000 patient-years), NNRTIs (7.5, 15.9, and 17.5 per 1000 patient-years), or INSTIs (13.0, 33.1, and 21.5 per 1000 patient-years). After inverse probability of treatment weighting, adjusted hazard ratios (95% confidence intervals) for MI, stroke, and all-cause mortality with ATV-containing regimens versus all non-ATV-containing regimens were 0.59 (0.41–0.84), 0.64 (0.50–0.81), and 0.90 (0.73–1.11), respectively.

Conclusion: Among treatment-naive HIV-infected patients in the Veterans Health Administration initiating ATV-containing regimens, risk of both MI and stroke were significantly lower than in those initiating regimens containing other protease inhibitors, NNRTIs, or INSTIs.

aDepartment of Pharmacotherapy, University of Utah College of Pharmacy

bInformatics, Decision-Enhancement, and Surveillance (IDEAS) Center, Salt Lake City VA Health Care System

cDepartment of Population Health Sciences, University of Utah, Salt Lake City, Utah

dBristol-Myers Squibb, Lawrenceville, New Jersey

eDivision of Epidemiology, Department of Internal Medicine, University of Utah, Salt Lake City, Utah

fDepartment of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.

Correspondence to Joanne LaFleur, PharmD, MSPH, Associate Prof, Department of Pharmacotherapy, University of Utah College of Pharmacy, LS Skaggs Jr Research Building, 30 S 2000 East #4765, Salt Lake City, UT 84112, USA. Tel: +1 801 585 3794; fax: +1 801 581 7442; e-mail: Joanne.Lafleur@pharm.utah.edu

Received 16 March, 2017

Revised 27 June, 2017

Accepted 27 June, 2017

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