The Bounce-Back Effect: What Happens After Cessation of Low-Dose Semaglutide in People with HIV

Abstract

Background: We previously reported reductions in weight and cardiometabolic risk factors in people with HIV (PWH) receiving semaglutide; here we explored the durability of these changes after treatment cessation.

Methods: ACTG A5371 enrolled PWH ≥18 years on suppressive antiretroviral therapy (ART) with metabolic dysfunction-associated steatotic liver disease. All received subcutaneous semaglutide 1 mg weekly for 24 weeks followed by 24 weeks off semaglutide. We measured weight and cardiometabolic risk factors (blood pressure, cholesterol, metabolic syndrome) at weeks 0, 24 and 48. Mean (95% CI) changes were estimated using linear regression.

Results: The 49 participants had median age 52 years, BMI 35 kg/m2, 39% Hispanic and 33% Black, 43% female. After the mean 7.8 kg (95% CI 6.1, 9.5) weight loss in the first 24 weeks, absolute mean weight regain from 24 to 48 weeks was +2.9 kg (CI 1.5, 4.3). Weight regain was accompanied by significant increases in waist circumference (2.0 cm [0.9, 3.1]) and fasting glucose (5.1 mg/dL [0.9, 9.3]) without significant changes in blood pressure, total or LDL cholesterol, triglycerides or metabolic syndrome.

Conclusions: Short-term, low-dose, semaglutide was associated with cardiometabolic benefit in PWH, but rapid weight regain and some loss of cardiometabolic benefit occurred after stopping semaglutide, similar to the general population. Further study of higher-dose semaglutide and strategies to maintain benefits following initial therapy are needed in PWH.

Keywords: GLP-1 receptor agonist; HIV; MASLD; weight regain.