Tenofovir alafenamide associated with metabolic complications in patients with HIV
1. Patients who switched to tenofovir alafenamide experienced significantly greater increases in weight and lipid levels compared to those who continued tenofovir disoproxil fumarate.
2. The frequency of new-onset diabetes appeared to be similar between groups.
Evidence Rating Level: 2 (Good)
Study Rundown: Tenofovir is a nucleoside reverse transcriptase inhibitor (NRTi) that is universally recommended as part of a first-line treatment regimen for human immunodeficiency virus (HIV). Tenofovir alafenamide (TAF) has widely replaced tenofovir disoproxil fumarate (TDF) in most guidelines on account of its more forgiving bone and renal safety profile. However, TAF has also been linked to concerning weight and metabolic changes in antiretroviral therapy (ART) naive patients. Currently, it is unclear whether these effects are attributable to a desirable reduction in infection-associated catabolism or to the drug itself. This study was conducted to differentiate between these two causes and assessed whether adults with HIV receiving TDF treatment experienced changes in weight and other metabolic outcomes after switching to TAF. TAF was found to be associated with a significant increase in weight, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride levels. This study was limited by a relatively short follow-up and an observational design. Nonetheless, the results underscored the importance of contextualizing the benefits and harms of TAF when tailoring ART to individual patients.
Click here to read the study in Annals of Internal Medicine
In-Depth [prospective cohort]: This prospective cohort study involved 4,375 adults who were enrolled in the ongoing Swiss HIV Cohort Study (SHCS). SHCS patients were eligible for inclusion if they were receiving a TDF-containing treatment for at least six months and either continued receiving TDF or switched to TAF. Patients who received NRTi between the use of TDF and TAF were excluded from the study. Of these 4,375 participants, 3,484 (79.6%) switched to TAF, and 891 (20.4%) continued TDF until the end of the study. At 18 months, those who switched to TAF had greater weight gain compared to those who continued TDF (between-group difference, 1.1 kg; 95% confidence interval [CI}, 0.7 to 1.4; P <0.001). This difference was independent of the third drug used (integrase strand transfer inhibitors, non-nucleoside reverse transcriptase inhibitors, or protease inhibitors) but varied according to race and sex. Among individuals with a normal BMI at the index visit, 13.8% of patients who switched to TAF became overweight or obese after 18 months compared to 8.4% of patients who continued TDF (difference, 5.4%; 95% CI, 2.1 to 8.8%). The crude incidence of new-onset diabetes was 1.1 per 100 person-years among those who switched to TAF compared with 0.9 per 100 person-years among those who continued TDF (unadjusted incidence rate ratio, 1.2; 95% CI, 0.6 to 2.6). Overall, patients who switched to TAF experienced significantly more weight gain and higher lipid levels compared to patients who maintained their TDF therapy.
Image: PD
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