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IAS 2025 Weight Management
Rethinking Weight Management in People Living With HIV: Perspectives From Australia on IAS 2025

Released: August 05, 2025

Gail Matthews
Gail Matthews, MD, PhD, Prof
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Key Takeaways
  • New evidence from IAS 2025 suggests that sociodemographic factors are more likely to contribute to significant weight gain than antiretroviral therapy usage in people living with HIV.
  • GLP-1 RAs show promise for weight loss and improvement of metabolic dysfunction among people living with HIV and obesity, but further evidence is needed amongst diverse populations.

Although much of the excitement at International AIDS Society (IAS) 2025 is related to HIV prevention, particularly the global implementation of long-acting injectables, strategies to improve the health and well-being of people living with HIV remain a major focus.

For many people living with HIV in Australia, the antiretroviral therapy (ART) regimen itself is less of a daily issue than is the increasing burden of comorbidities faced by an aging population.

Managing Metabolic Dysfunction and ART
Obesity, metabolic dysfunction, and cardiovascular disease continue to be major drivers of morbidity, likely moderated by both HIV- and non-HIV–related risk factors. In fact, obesity currently affects approximately 60% of all Australian adults, and recent studies found that people living with HIV in Australia have rates of obesity similar to people without HIV. With these factors in mind, understanding how HIV treatment could contribute to weight gain and obesity has become a priority.

The relative contribution of specific ART medications to weight gain has long been disputed. Predictors of weight gain were examined in the TRIO cohort, a retrospective cohort of over 10,000 people living with HIV extracted from electronic medical records in the United States. Focusing on those with significant weight gain over 3 years (defined as a 10% or more increase in weight with either a shift to a higher BMI or obesity at baseline), investigators determined that 12% of virologically suppressed people living with HIV fit this category. Using a case-control design with 2 different methodologies—machine learning and logistic regression—investigators determined that predictive factors of significant weight gain were predominantly sociodemographic: Younger age, Black race, female sex, and lower CD4 counts were all associated with significant weight gain. On the other hand, ART usage had minimal impact.

This was further supported by data from the DO-IT trial (ACTG 5391). In this randomized, open-label study, people living with HIV with baseline obesity (BMI ≥30kg/m2) and on a combination of an integrase strand transfer inhibitor (INSTI) and tenofovir alafenamide (TAF) or emtricitabine (FTC) were randomized to 1 of 3 arms: doravirine (an NNRTI) with tenofovir disoproxil fumarate (TDF)/FTC; doravirine with TAF/FTC; or to remain on their current INSTI + TAF/FTC. The study prespecified that a minimum of 50% of participants should be female and Black. There were 145 participants recruited from 25 sites across the United States. At baseline, median BMI was 34.9 kg/m2, 86% were on bictegravir, and all had good HIV control. Over 48 weeks, some weight loss was observed in all arms, likely because of study engagement, but no evidence of any benefit for ART switch was observed, including by subgroup such as race and sex.

Increasing evidence suggests that it is unlikely that, irrespective of any underlying contribution of HIV or ART, manipulation of antiretroviral drugs will improve obesity. This is an important message to communicate to patients, alongside a renewed focus on identification and proactive management of individuals at higher risk of HIV exposure.

GLP-1 Receptor Agonists for Obesity in People Living With HIV
Much attention in both science and social media has been given to the GLP-1 receptor agonist class of weight loss drugs. Although widely used and studied within the general population, the evidence in people living with HIV remains limited. A late-breaking poster at IAS 2025 provided some additional data in African patients. In a small study of 40 people living with HIV and obesity (BMI ≥30 kg/m2) from South Africa, liraglutide at a dose of 3.0 mg per day for 12 weeks resulted in a mean weight loss of 3.1 kg, along with improvements in other metabolic markers, and was highly acceptable to patients. These data add to the evidence base for these agents which should be further explored amongst diverse populations and settings.

Ultimately, we must remember that the focus should be on improving health outcomes for people living with HIV, not stigmatization of body size. The social construct of obesity, its origins and impact, requires thoughtful interpretation rather than a one-size-fits-all biomedical approach.

Your Thoughts
How do you approach balancing HIV treatment and management of HIV- and non-HIV–related comorbidities? Do you believe that weight gain on ART is an important concern to discuss with your patients? Leave a comment to join the discussion!

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