For 34-year-old Black South African women living with HIV, treatment options have long been limited to a combination of three drugs — tenofovir, lamivudine, and dolutegravir. But a new study published in JAMA in 2026 suggests there is now another option that works just as well while causing much less weight gain.
Researchers in South Africa ran a clinical trial called the OPTI-DOR study to compare a three-drug regimen including a newer medication called doravirine against the current gold-standard treatment, dolutegravir. The Africa Health Research Institute (AHRI) ran part of the trial in rural northern KwaZulu-Natal province, while another site operated in Gauteng. Altogether, 600 adults living with HIV took part — half received doravirine and half received dolutegravir.
The results showed that doravirine worked just as well as dolutegravir at keeping HIV viral load suppressed. But the most striking difference was in weight. After 48 weeks, participants taking doravirine gained a median of 3 kilograms (about 6.6 pounds), while those on dolutegravir gained 5 kilograms (about 11 pounds) — nearly double. Body fat increases were also lower with doravirine: 1.5 percent versus 2.2 percent.
Dr. Joana Woods, lead author and senior research clinician at Ezintsha at the University of the Witwatersrand, said the findings are especially important because second-generation HIV medicines like dolutegravir have been linked to significant weight gain and obesity, particularly among women and Black populations. Excess weight can lead to diabetes, heart disease, and other long-term health problems.
Professor Limakatso Lebina, who led the rural trial site at AHRI-Somkhele, said the results could be a game changer for patients who struggle with treatment-related weight gain while still needing effective HIV control. She noted that the mix of rural and urban participants makes the findings relevant across different South African communities.
One important caveat: doravirine only works well if taken every single day as prescribed. Missing doses can lead to drug resistance, meaning the medicine stops working against the virus. Woods emphasized that adherence is key.
Looking ahead, researchers hope these findings will give doctors and patients a new first-line option that protects both HIV control and long-term metabolic health.