Tenofovir Disoproxil Fumarate Linked to Less HIV Metabolic, BMI Risk than Tenofovir Alafenamide

A new cohort analysis suggests replacing tenofovir disoproxil fumarate (TDF) with tenofovir alafenamide (TAF) is hamrful for metabolic and weight-based outcomes among patients with HIV.

In new research published to the Annals of Internal Medicine, a team of investigators from Switzerland show the profile of benefit with the antiretroviral therapy (ART) regimen TDF goes beyond previously observed efficacy in renal and bone safety outcomes.

As the guideline-established frontline ART for HIV, tenofovir’s utility appears to be refined as TDF (Viread), a therapy with marketed benefit for hepatitis B virus as well.

Though its efficacy in particular HIV comorbid outcomes was already evidenced, the effect of TDF on metabolic complications and risks was not well known—and previously was a concern to investigators.

Led by Bernand Surial, MD, of Bern University Hospital, the investigators sought to assess weight changes, development of overweight and obese body mass index (BMI), and changes in lipid levels among patients switched from TAF to TDF. The cohort assessment ran for 18 months.

The trial population included 4375 adults living with HIV who received TDF with ART for ≥6 months. They were recruited from 5 university hospitals, affiliated instituions, and private physicians in Switzerland.

Weight and lipid level changes were observed via mixed-effect models, and differences in the proportion of newly overweight and/or obese patients with HIV were calculated with 2-proportions Z tests.

Patient follow-up was conducted from January 2016 through July 2019. Among the observed patients, median age was 50 years old (interquartile range [IQR], 43-56). Just 25.9% of patients were female, and a slight majority (51.7%) had a normal BMI.

Nearly four-fifths (n = 3484, 79.6%) switched from TDF to TAF, and 891 (20.4%) continued TDF for their ART regimen.

At 18 months, switching to TAF was linked to an adjusted mean weight increase of 1.7 kg (95% CI, 1.5 – 2.0), versus just 0.7 kg (95% CI, 0.4 – 1.0) with continued use of TDF. Among the participants with a normal BMI at baseline, 13.8% who switched to TAF became overweight or obese, versus 8.4% of those who remained on TDF, for a difference of 5.4 percentage points (95% CI, 2.1 – 8.8).

Surial and colleagues also observed increased in adjusted mean total cholesterol (9.5 mg/dL), high-density lipoprotein cholesterol (HDL-C; 1.9 mg/dL), low-density lipoprotein cholesterol (LDL-C; 4.7 mg/dL), and triglyceride (16.1 mg/dL) levels after 18 months.

Though the investigators faced study limitations in a short follow-up period relative to the outcomes, a small subgroup analysis, and potential residual confounding, the outcomes were supportive of more comorbid benefits associated with TDF versus TAF.

“Replacing TDF with TAF is associated with adverse metabolic changes, including weight increase, development of obesity, and worsening serum lipid levels,” they concluded.