Cardiovascular outcomes among HIV-infected veterans receiving atazanavir

Abstract

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.

Risk of myocardial infarction among people living with HIV: an updated systematic review and meta-analysis

“…Three studies did not provide sufficient information necessary to assess the study quality, as they were reported and available as conference abstract/poster 55 57 63. The eligibility criteria were clearly defined in the majority of studies (94%), description of study participants/ groups was sufficient (100%); however, the exposure or outcome was not adequately ascertained in 15 studies (47%)8 12 24 52 54 56 60 63–70; 1 (7%) of which was published as an abstract63 (see online supplementary appendix table 3: risk of bias in the included studies).…”

“…When the analysis was limited to two studies comparing recent PI exposure to no exposure,3 63 similar results were found (RR: 1.40; 95% CI 1.16 to 1.69 (data not shown)). For the individual PIs, there was no association between either atazanavir,52 64 66 68 saquinavir,52 68 or nelfinavir exposure,52 68 and MI risk, compared with no exposure (online supplementary appendix figure A4).…”

Ten Years of Atazanavir Experience A history page of antiretroviral treatment

“…The average duration of HIV diagnosis until the beginning of the ATV regimen was 7.1 ± 6.8 years, with variations from a few weeks to 26 years. Choosing ATV therapies were justified as following: 26.6% guidelines recommendations for the first-line ARV, 46.6% failures of previous therapy, 18.3% adverse events of previous therapy, especially metabolic and cardiovascular events, 8.3% improving convenience for better adherence of experienced patients [9] .The pre-existing cardiovascular co-morbidities that counted for choose ATV as preferred PI were hypertension (18/60), cardiomyopathy (4/60), myocardial infarction (1/60), ischemic heart disease (2/60) and stroke (1/60) [10,11]. Combination antiretroviral therapies can be atherogenic and could increase stroke risk.…”

“…Therapies with ATV were initiated from 2009 until 2016, when updated recommendations of treatment guidelines for the first-line antiretroviral have been preferred other novel drugs [10].…”

Drug–drug interactions and clinical considerations with co-administration of antiretrovirals and psychotropic drugs

“…100 Some analyses suggest that among the PIs, atazanavir may be preferred as a lower-risk option. 101,102 Careful assessment of cardiovascular risk factors in these patients, including initiation of primary prevention therapies as indicated, is warranted.…”