For millions living with HIV, the daily pill has become a lifeline. But for some, it can come with a hefty side effect: extra kilos that pile up over time and can bring diabetes, high blood pressure and heart disease closer.
If you’re a black, 34-year-old South African woman living with HIV, antiretroviral (ARV) treatment options have likely been limited to tenofovir disoproxil fumarate (TDF), lamivudine (3TC) and the ‘gold standard’ dolutegravir (DTG). Until now.
At the 2026 International Aids Society Conference on HIV Science, and published in the Journal of the American Medical Association, it was announced that South African researchers have found a potentially important alternative — an HIV treatment that suppresses the virus as effectively as the widely used “gold standard” drug dolutegravir, but with significantly less weight gain.
The South African Opti-DOR study results could give doctors another HIV-treatment option, particularly for people at greater risk of gaining weight on newer-generation ARVs.
The study involved 600 South Africans living with HIV who were randomly assigned to one of two daily three-drug treatment combinations.
One group received tenofovir disoproxil fumarate, lamivudine and doravirine, while the other received tenofovir alafenamide, emtricitabine and dolutegravir.
Dolutegravir, or DTG, has become a mainstay of HIV treatment because of its powerful ability to suppress the virus.
The study found doravirine was non-inferior to dolutegravir ― meaning it worked just as well at suppressing HIV.
After 48 weeks, the virus was suppressed in 89% of people taking doravirine, compared with 90.7% of those taking dolutegravir.
But there was a significant difference when researchers looked at weight.
The average weight gain among those taking doravirine was 3kg after 48 weeks, compared with 5kg among those taking dolutegravir.
There was also less of an increase in body fat, with participants gaining 1.5% with doravirine compared to 2.2% with dolutegravir.
Dr Joana Woods, senior research clinician at Ezintsha at Wits University and lead author of the study, said the finding was significant because newer HIV medicines such as dolutegravir and bictegravir have been associated with substantial weight gain and new-onset obesity.
The problem has been particularly pronounced among women and black populations, she said.
[...] If you can start an ARV that’s not going to cause as much weight gain, or not cause weight gain at all, or have an alternative, that would be first prize. And that’s the premise of this study.
— Dr Joana Woods, senior research clinician
“Although second-generation ARVs such as dolutegravir and bictegravir are highly effective HIV medicines, they have been consistently associated with substantial weight gain and new onset obesity, particularly among women and black populations and especially when combined with TAF,” Woods said.
That extra weight is not just a cosmetic worry. Excess weight can increase a person’s risk of diabetes, hypertension, cardiovascular disease and other non-communicable diseases.
For South Africa, where both HIV and non-communicable diseases are major health challenges, researchers say avoiding unnecessary weight gain could make a meaningful difference to patients’ long-term health.
“So if you can start an ARV that’s not going to cause as much weight gain, or not cause weight gain at all, or have an alternative, that would be first prize. And that’s the premise of this study,” Woods said.
The trial was deliberately conducted across both rural and urban South Africa.
The Africa Health Research Institute (AHRI) enrolled 178 participants at its Somkhele site in rural northern KwaZulu-Natal between December 2023 and March 2025, with the remaining participants recruited at the Johannesburg site.
Professor Limakatso Lebina, principal investigator at the rural AHRI-Somkhele study and director of science at AHRI, said this gave the researchers confidence that the results reflected different South African communities.
“By including participants from both rural KwaZulu-Natal and urban Gauteng, we can be confident that these findings are relevant to people living with HIV in different communities across South Africa,” she said.
However, there is a catch. Doravirine needs to be taken consistently. If patients fail to take it properly, HIV can develop resistance to the drug, potentially making it ineffective. This became apparent when seven people in the study developed resistance. They were switched to dolutegravir and successfully suppressed the virus again.
Woods stressed that doravirine should not be seen as a replacement for dolutegravir.
“It is not a replacement. It has to be targeted to patients who are at risk of gaining more weight ― and complications thereof,” she said.
The study also found that changes in blood fats, or lipids, favoured doravirine. Blood sugar measurements and blood pressure were similar in both groups.
However, bone mineral density declined more among those taking doravirine, another consideration for doctors and patients.
Doravirine is already registered and available in South Africa. The researchers have alerted the National department of health and the South African Health Products Regulatory Authority to the findings.
For Woods, the significance of the study comes down to choice. Treatment needs to be as effective and manageable as possible for people who have to take it every day.
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