Doravirine Matches Dolutegravir Efficacy While Cutting Weight Gain in HIV Treatment
A randomized trial finds doravirine-based ART suppresses HIV as effectively as dolutegravir but causes significantly less weight gain.
Summary
A randomized trial of 600 treatment-naive HIV patients in South Africa found that a doravirine-based antiretroviral regimen suppressed the virus just as effectively as the standard dolutegravir-based approach, while causing meaningfully less weight gain. After 48 weeks, viral suppression rates were nearly identical (89% vs 90.7%), but median weight gain was 3.0 kg with doravirine versus 5.0 kg with dolutegravir. Body fat percentage increases were also lower with doravirine. Researchers suggest this alternative regimen could help prevent obesity and reduce cardiometabolic risk in patients where weight management is a priority — particularly women and Black patients, who face higher risk of irreversible weight gain on standard INSTI-based therapies.
Detailed Summary
Weight gain is one of the most clinically significant side effects of modern HIV treatment, and it may be easier to prevent than to reverse. Standard first-line antiretroviral regimens built around integrase strand transfer inhibitors (INSTIs) like dolutegravir are highly effective at suppressing HIV, but they are consistently linked to substantial weight gain — especially when paired with tenofovir alafenamide. This weight gain is often irreversible, even after switching regimens, making the initial treatment choice critically important.
The Opti-DOR trial, presented at the International AIDS Conference and simultaneously published in JAMA, tested whether a doravirine-anchored regimen could match dolutegravir's antiviral power while limiting weight gain. Among 600 treatment-naive adults in South Africa, 89% taking doravirine, lamivudine, and tenofovir disoproxil fumarate achieved viral suppression below 50 copies/mL at 48 weeks, compared with 90.7% on the dolutegravir-based regimen — meeting the prespecified noninferiority threshold.
On cardiometabolic outcomes, doravirine showed a clear advantage. Median weight gain was 3.0 kg versus 5.0 kg in the dolutegravir group, a statistically significant difference. Total body fat percentage increases were also lower: 1.5% versus 2.2%. CD4 cell count recovery was equivalent between groups, confirming comparable immune reconstitution.
The patient population was nearly entirely Black African, median age 34, and 68.8% were women — groups known to be at elevated risk for INSTI-associated weight gain. Researchers emphasized that viral suppression remains the primary goal, but for patients where obesity or cardiometabolic risk is a concern, doravirine offers a clinically viable alternative.
Important caveats apply: this is a 48-week dataset from two South African sites, and longer-term durability, resistance patterns, and generalizability to other populations remain to be established. Doravirine is not positioned as a universal replacement for INSTI-based therapy.
Key Findings
- Doravirine-based ART achieved 89% viral suppression vs 90.7% for dolutegravir, meeting noninferiority at 48 weeks.
- Median weight gain was significantly lower with doravirine: 3.0 kg vs 5.0 kg (p<0.001).
- Total body fat percentage increase was 1.5% with doravirine vs 2.2% with dolutegravir.
- CD4 cell count recovery was equivalent between regimens, confirming comparable immune benefit.
- Women and Black patients face highest risk of irreversible INSTI-related weight gain, making regimen choice critical.
Methodology
This is a meeting coverage news report summarizing an open-label randomized controlled trial (Opti-DOR) of 600 participants across two South African sites. Results were simultaneously published in JAMA, a high-credibility peer-reviewed journal. Evidence quality is strong for an ART comparison trial, though the open-label design introduces potential bias.
Study Limitations
The 48-week follow-up period may not capture long-term resistance emergence or sustained weight outcomes. The trial was conducted at only two South African sites with a nearly exclusively Black African cohort, limiting generalizability. Full published data in JAMA should be consulted for complete safety profiles and subgroup analyses.
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