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

Background: 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. Methods: 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. Results: 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/m 2 , 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/m 2 ), 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. Conclusions: 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.