Initial HIV Therapy for Adults and Treatment-Associated Weight Gain
JAMA · 31 Jul 2026
† Impact is the editorial-priority score. All scores are out of 100. Clinical is a stored clinical-importance score from the earlier method; it has not been recalculated.
Why it matters
Weight 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.
The evidence
This randomised 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.
Viral suppression (HIV RNA <50 copies/mL) at week 48: Risk difference -1.7 (95% CI -6.6 to 3.1; units not reported). The effect units are insufficient for a directional interpretation.
Why this rigour score?
Multicentre RCT
Methods at a glance
Recorded assessment- Outcome assessors blindedNot met
- Allocation concealedMet
- Random sequence generatedMet
- Intention-to-treat analysisMet
- Adequate statistical powerMet
- Prospective registrationMet
Not reported does not mean not done. Checks have different weights; this is not a count of boxes ticked.
How to read this assessment
The recorded methods are shown alongside the published score. A verified point-by-point calculation is not available for this version of the appraisal.
Checklist from the stored appraisal. “Not met” describes the recorded criterion; it does not always produce a deduction. This overview supports reading the full study.
For journal club
1.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?
2.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 counselling patients?
Original publication title
Initial HIV Therapy for Adults and Treatment-Associated Weight Gain