Understanding ART-Associated Weight Gain

Recent clinical evidence highlights ART-associated weight gain as a significant challenge for people living with HIV (PLWH) starting therapy. While antiretroviral therapy (ART) effectively suppresses viral load, specific drug classes appear to influence body mass index differently. Consequently, clinicians must balance virological efficacy with long-term metabolic health. This study evaluates how contemporary integrase strand transfer inhibitors (INSTIs) and tenofovir alafenamide (TAF) contribute to this phenomenon compared to older regimens.

Risk Factors and ART-Associated Weight Gain

Researchers found that participants initiating INSTI-based regimens experienced a mean weight gain of 4.9 kg over two years. In contrast, those starting non-nucleoside reverse transcriptase inhibitors (NNRTIs) gained significantly less, averaging 2.7 kg. Furthermore, the specific choice of INSTI drug mattered. Bictegravir showed the highest numerical gain at 6.9 kg, followed by dolutegravir at 5.3 kg. These findings suggest that ART-associated weight gain is not a class-wide effect but varies by specific agent potency and individual metabolic profiles.

Impact of NRTI Backbone and Demographics

Additionally, the nucleoside reverse transcriptase inhibitor (NRTI) backbone plays a critical role in metabolic outcomes. Patients receiving TAF in combination with INSTIs gained more weight than those on tenofovir disoproxil fumarate (TDF). Notably, demographic factors also influenced these results. Black females starting TAF with contemporary INSTIs faced the most substantial increases, reaching up to 10.0 kg at two years. Therefore, personalized monitoring is essential for high-risk populations to mitigate potential metabolic complications.

Frequently Asked Questions

Which antiretroviral drugs are most linked to weight gain?

Contemporary INSTIs, particularly bictegravir and dolutegravir, are linked to the highest weight increases. When these agents are paired with tenofovir alafenamide (TAF), the effect is often amplified compared to older drug combinations like those containing TDF or efavirenz.

Why is weight gain more significant in certain populations?

Studies indicate that biological factors, including race and sex, influence metabolic responses to ART. Black females appear to be at the highest risk for significant weight gain when starting modern INSTI and TAF-based regimens.

Disclaimer: This content is for informational and educational purposes only and does not constitute medical advice, diagnosis, or treatment. Always seek the advice of a qualified healthcare provider with any questions regarding a medical condition. Refer to the latest local and national guidelines for clinical practice.

References

Bourgi K et al. Weight Gain on Contemporary Integrase Strand Transfer Inhibitors and Tenofovir Alafenamide in Persons with HIV Starting Antiretroviral Therapy in the United States and Canada. J Infect Dis. 2026 May 29. doi: undefined. PMID: 42216675.

Sax PE, et al. Weight Gain Following Initiation of Antiretroviral Therapy: Risk Factors in Randomized Comparative Clinical Trials. Clin Infect Dis. 2020;71(6):1379-1389.

Surial B, et al. Weight change and metabolic outcomes after switching from TDF to TAF: a population-based cohort study. Ann Intern Med. 2021;174(6):758-767.