SA study finds doravirine works as well as dolutegravir to suppress HIV viral load, enabling choice for those living with HIV
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)
Now, another once-a-day, three-drug regimen has been found to be as effective as DTG in supressing HIV viral load
Not only is the once daily regimen of tenofovir disoproxil fumarate (TDF), lamivudine (3TC) and doravirine non-inferior to DTG, it is associated with significantly less weight gain and has a better lipid profile than the combination favoured and recommended as first-line in many countries, and increasingly in low-and-middle income countries
These were the end point findings of the South African Opti-DOR study presented at the 2026 International AIDS Society Conference on HIV Science on 31 July and published in the Journal of the American Medical Association (JAMA)
Dr Joana Woods, Senior Research Clinician at Ezintsha at the University of the Witwatersrand (Wits) and lead author, says: “The findings are important because 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. This has raised concern about long-term cardiometabolic risk, including diabetes and cardiovascular disease.”
Research consistently confirms that if you gain excess weight, it puts you at risk of diabetes, hypertension, cardiovascular disease, and other non-communicable diseases (NCDs)
In primary healthcare, prevention is better than having to deal with long term consequences. This is why in a country like South Africa with widespread HIV and NCDs, managing weight gain in people living with HIV is critical to their 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,” says Woods
About the OPTI-DOR Study
The Africa Health Research Institute (AHRI) ran the rural arm of the Opti-DOR study at AHRI-Somkhele site in rural northern KwaZulu-Natal province
“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,” says Professor Limakatso Lebina, director of science at AHRI
The AHRI site enrolled 178 participants between December 2023 and March 2025, with the Johannesburg site enrolling the rest, for a total of 600
Participants were randomised in a 1:1 ratio to receive either oral daily doravirine (TDF/3TC/DOR) or dolutegravir (TAF/FTC/DTG)
Weight gain differed significantly between the two study groups. Median weight gain at week 48 was 3.0 kg with doravirine (TDF/3TC/DOR) compared with 5.0 kg with dolutegravir (TAF/FTC/DTG)
Increases in total body fat percentage were also significantly lower with doravirine (TDF/3TC/DOR) at 1.5%, versus 2.2%
“These results add some clarity to a challenge that has frustrated both doctors and patients for years: how to treat HIV effectively without causing significant weight gain,” says Lebina. “For many patients, especially black women who are disproportionately affected by treatment-associated weight gain, this could be a game changer. It offers an important new treatment option that supports long-term health while maintaining excellent HIV control.”
Non-inferior yet drug resistance
Woods emphasises that the efficacy of doravirine is dependent on patients’ absolute adherence to taking it. If doravirine is taken properly, HIV viral load will be suppressed. However, failure to adhere can cause drug resistance
“Doravirine is non-inferior to dolutegravir in the sense that if you take the drug properly, you will suppress it [HIV viral load]. If you don’t take it properly, you will likely become resistant. That unfortunately is one of the downsides of using doravirine.”
In the Opti-DOR clinical trial, seven patients developed resistance to the drug. These participants were then switched over to dolutegravir and successfully suppressed again
Woods emphasises that doravirine is unlikely to be a replacement for DTG: “It is not a replacement. It has to be targeted to patients who are at risk of gaining more weight – and complications thereof.”
Despite drug resistance, the data prove that doravirine is not inferior to dolutegravir and that it causes less weight gain
Research into action
Doravarine is already an available and registered drug
The researchers have alerted the South African National Department of Health and the South African Health Products Regulatory Authority
“Imagine you’re a diabetic and you only have access to one drug? It’s the same thing with HIV. Yes, the drug they have at the moment is really top of the tops, but it doesn’t suit everybody. You have to have options. Until we can cure HIV, you’ve got to make it as easy as possible for people to take their treatment. That’s what it comes down to.”
