Association of Tenofovir Use With Risk of Incident Heart Failure in HIV‐Infected Patients

Abstract

BackgroundThe antiretroviral medication, tenofovir disoproxil fumarate (TDF), is used by most human immunodeficiency virus–infected persons in the United States despite higher risks of chronic kidney disease. Although chronic kidney disease is a strong risk factor for heart failure (HF), the association of TDF with incident HF is unclear.Methods and ResultsWe identified 21 435 human immunodeficiency virus–infected patients in the United States Veterans Health Administration actively using antiretrovirals between 2002 and 2011. We excluded patients with a prior diagnosis of HF. TDF was analyzed categorically (current, past, or never use) and continuously (per year of use). Proportional hazards regression and fully adjusted marginal structural models were used to determine the association of TDF exposure with risk of incident HF after adjustment for demographic, human immunodeficiency virus–related, and cardiovascular risk factors. During follow‐up, 438 incident HF events occurred. Unadjusted 5‐year event rates for current, past, and never users of TDF were 0.9 (95%CI 0.7‐1.1), 1.7 (1.4‐2.2), and 4.5 (3.9‐5.0), respectively. In fully adjusted analyses, HF risk was markedly lower in current TDF users (HR=0.68; 95%CI 0.53‐0.86) compared with never users. Among current TDF users, each additional year of TDF exposure was associated with a 21% lower risk of incident HF (95%CI: 0.68‐0.92). When limited to antiretroviral‐naive patients, HF risk remained lower in current TDF users (HR=0.53; 95%CI 0.36‐0.78) compared to never users.ConclusionsAmong a large national cohort of human immunodeficiency virus–infected patients, TDF use was strongly associated with lower risk of incident HF. These findings warrant confirmation in other populations, both with TDF and the recently approved tenofovir alafenamide fumarate.

Protease Inhibitors and Cardiovascular Outcomes in Patients With HIV and Heart Failure

“…The level of viral suppression may be inferior to that noted in more updated registries and clinical trials. However, this level of viral suppression is comparable to that reported in other contemporary observational clinical cohort studies (56% to 62%) (11,20,22), and the viral suppression reported in our study is similar to that reported in a study by Hanna et al (39) involving more than 7,196 PHIV from the same geographic location during the same time period (66%). Therefore, a potential explanation for the worse outcomes in PHIV is poor adherence to treatment for either HIV or HF.…”

“…There are no data on the association between PI-based regimens and outcomes specifically among PHIV with HF, a group at high risk of adverse events. Chen et al (20), in a study involving 21,435 PHIV, demonstrated an association between current use of tenofovir (a nucleoside reverse transcriptase inhibitor) and an approximately 30% to 40% lower risk of incident HF compared with past users or never users of this drug. In that study, patients with HF were excluded, and the effect of PI regimens was not the focus; however, a significant proportion of the comparator group was prescribed a PI-based ART regimen.…”

Incidence, Predictors, and Outcomes of Implantable Cardioverter‐Defibrillator Discharge Among People Living With HIV

“…Furthermore, the overall viral suppression rate in this study was 51%. This rate of viral suppression is comparable to other contemporary observational clinical cohort studies (suppression rates of 45%–62%)1, 5, 38 and studies in this region (viral suppression rate of 58%),39 but is lower than observed in more recent registries and clinical trials 40, 41, 42. It is also possible that the PHIV with an ICD were sicker for other reasons, such as concomitant infections/lower CD4 cell count, and therefore more likely to have an ICD discharge.…”

Treatment with tenofovir alafenamide fumarate worsens the lipid profile of HIV‐infected patients versus treatment with tenofovir disoproxil fumarate, each coformulated with elvitegravir, cobicistat, and emtricitabine

“…Among a large cohort of HIV‐infected patients actively using antiretrovirals between 2002 and 2011, TDF use was strongly associated with lower risk of heart failure incidents. Compared with never users of TDF, current users of TDF and patients whose initial regimen included TDF had reductions in heart failure risk ranging from 30% to 50%.…”

“…Among the NRTIs, tenofovir disoproxil fumarate (TDF) was approved by the American and European drugs regulatory authorities and was available for HIV treatment in 2002. Since its approval, this drug has been included in most recommended regimens and has been the most widely used NRTI for many years based on its established high efficacy and generally good tolerance, as demonstrated in clinical trials and real‐life studies …”