JAMA · IF 65.4 · July 31, 2026 · LoE I
Initial HIV Therapy for Adults and Treatment-Associated Weight Gain
Joana Woods, Limakatso Lebina, Karlien Möller, Willem Daniel Francois Venter, Godspower Akpomiemie, Ncomeka Manentsa, Ineeleng Taukobong, Philadelphia Macholo, Ngundu Osee Behuhuma, Samanta Tresha Lalla-Edward, Jen Manne-Goehler, Mark J. Siedner — University of the Witwatersrand
This randomized trial in South Africa compared two first-line HIV drug regimens in 600 antiretroviral-naive adults: one containing doravirine/lamivudine/tenofovir disoproxil fumarate versus the current standard dolutegravir/emtricitabine/tenofovir alafenamide. At 48 weeks viral suppression was similar between groups (89.0% vs 90.7%, meeting the noninferiority margin), but the doravirine-based regimen caused significantly less weight gain (median 3.0 kg vs 5.0 kg, difference -2.0 kg, P<.001), at the cost of greater bone mineral density loss and more resistance emergence among those who failed treatment.
AI summary · from the full text · reviewed by Pukhraj Gaheer, Medical Student, Queen's University before publishing
Why it mattersWeight gain from modern HIV regimens is a major cardiometabolic concern worldwide, and this is the first head-to-head RCT designed specifically to test whether an alternative first-line regimen can reduce that risk without sacrificing viral control.
Conclusion strengthPotentially practice-changing
Not significant, but the 95% CI -6.6 to 3.1 still allows a difference bigger than a 5-point absolute difference of 5 — inconclusive, not negative.
Presenting this at rounds? Start here
- ?If a patient starting HIV treatment is already overweight or obese, should regimen choice now factor in expected weight gain rather than defaulting to the standard dolutegravir/tenofovir alafenamide combination?
- ?Given the bone density loss and resistance signal seen with the doravirine-based regimen, how should clinicians weigh metabolic benefits against these competing risks when counseling patients?