Can switching to doravirine/lamivudine/tenofovir DF halt or reverse INSTI-associated weight gain?

In randomized trials, doravirine (DOR) appears relatively weight-neutral, while tenofovir DF (TDF) may be weight-suppressive. Here we designed a prospective, observational pilot study to assess the impact of switching to DOR/3TC/TDF on weight trajectory in patients with significant integrase inhibitor (INSTI)-associated weight gain.

Adults with a ≥10% increase in body weight while on an INSTI (± tenofovir alafenamide) regimen and HIV RNA <50 copies/mL were switched to DOR/3TC/TDF for 12 months. Weight, waist circumference, and routine bloodwork were measured at baseline and every 12 weeks. Total body fat (DXA scan) and body image/self-esteem (B-WISE, modified Fat Redistribution and Metabolic Change in HIV questionnaires) were assessed at baseline and week 48. The target enrolment was 25 participants.

Between September 2021 and September 2023, four participants were enrolled, with the results available for three women (Black, age 51/56/70 years, BMI 45.3/33.9/30.8 kg/m², 56%/45.7%/50% total body fat, with a 10%/13%/18% weight increase on the INSTI-regimen for 5.5/4.25/4.5 years). At 12 months, reductions in weight (0%/-7.5%/-6.7%), BMI (0/-2.6/-2 kg/m²), waist circumference (-0.8/-1.1/+1 cm), total body fat (-1.5%/-2.9%/-3.5%), blood pressure, fasting glucose, and lipids were observed. Body image/self-esteem improved; all maintained HIV RNA <50 copies/mL with no proteinuria/significant eGFR change. The study was closed due to futility in attaining timely target enrolment.

Two out of three Black women with a ≥10% INSTI-associated increase in body weight had weight loss of >5% after switching to DOR/3TC/TDF for 48 weeks. All three participants experienced small improvements in waist circumference, body fat, and metabolism, and all reported improvements in body image/self-esteem. Pandemic challenges significantly impacted the ability to enrol participants.