What breakthrough weight loss meds might mean for people with HIV
Weight gain and obesity are now commonly seen in people living with HIV (Photo: Unsplash)In part 3 of a Spotlight special series on the role of new weight loss medicines like Ozempic in South Africa, we ask what these breakthrough jabs might mean for people living with HIV in the country. There is some tantalising early research on potential benefits, but also many uncertainties.
In South Africa, HIV has long been associated with weight loss and wasting. Memories of the severe weight loss seen during the early HIV/AIDS epidemic, before treatment was widely available, remain embedded in public perceptions of HIV.
Yet, as more people have started taking HIV treatment and treatment regimens have evolved, weight gain and obesity are now commonly seen in people living with HIV. In fact, there is evidence that obesity disproportionately affects black women living with HIV.
“The mechanisms underlying greater weight gain in Black and female patients are currently unknown, but the fact that this population is most affected both by the HIV and the obesity epidemics, may represent one of the biggest public health challenges for areas with high HIV prevalence,” concludes a study led by the Desmond Tutu Health Foundation’s Dr Nomathemba Chandiwana.
Research on the impact of changing HIV treatment regimens on people’s weight, as well as research on diet and lifestyle interventions have shown that these changes alone have limited long-term impact on bodyweight. Weight loss medicines and surgery are therefore increasingly recommended alongside diet and lifestyle changes.
Rising rates of age and weight-related illness in people with HIV
As rates of obesity have risen in people with HIV, so too have weight-related diseases such as diabetes and heart, kidney, and liver disease. This is particularly worrying as people living with HIV are already predisposed to develop many of these conditions at younger ages than people without HIV.
As people age, they naturally become more prone to developing health conditions associated with aging, including heart disease, diabetes, and cancer. Many of the conditions associated with ageing are also linked to obesity – meaning the risks of developing a wide spectrum of health conditions are heightened by both aging and obesity. Add HIV to the mix, and risks climb further.
Most of the health risks associated with HIV infection can be reduced to very low levels with antiretroviral therapy, ideally started as soon after infection as possible. But even when on treatment, people living with HIV can have low-level chronic inflammation that can cause problems. The persistence of such chronic HIV-related inflammation that continues even after the virus is well controlled by treatment is understood to be a key driver of what researchers call advanced aging (vulnerability to age related disease at younger ages than people without HIV).
HIV scientists understand that this chronic inflammation is linked to the depletion of important immune cells and the continued presence of the HIV virus in one’s gut, even after one is stable on treatment, explains Dr Jenn Manne-Goehler, assistant professor at Harvard Medical School.
What research has been done and what has it shown?
Despite the urgent need for new tools to tackle obesity and weight-related illness in people with HIV, and the tantalising promise of GLP-1 medicines like semaglutide (sold as Ozempic and Wegovy) and tirzepatide (sold as Mounjaro and Zepbound), there has been very little research to date on GLP-1 use in people with HIV.
The research that has been done so far suggests that GLP-1s work similarly in people with HIV as they do in people without HIV. According to the European AIDS Clinical Society, “[t]he expected weight loss [from GLP-1s] in people with HIV is no different from that observed in the general population”.
Research also indicates that GLP-1s are generally safe to use in people with HIV. However, more research is needed to better understand and manage the risks of these drugs in people with HIV and to optimise their use alongside HIV medicines.
Only three clinical trials have been conducted to date looking at the use of GLP-1s in people with HIV. These three trials have cumulatively included less than 200 people, Chandiwana tells Spotlight.
Only one of the trials was placebo controlled and two used GLP-1s at lower doses than those recommended for weight management, notes Manne-Goehler. GLP-1s are used at higher doses for weight management than for diabetes.
Two of the three trials were conducted in the United States and investigated the use of low-dose semaglutide in people with HIV. The third trial was conducted in South Africa in Matubatuba in rural KwaZulu-Natal.
In this South African study, researchers investigated the use of weight management doses of liraglutide, an older GLP-1 medicine that is generally more affordable than newer agents, but results in less weight loss and requires daily rather than weekly injections. Manne-Goehler was the primary investigator for this study. No clinical trials of tirzepatide have been conducted in people with HIV to date.
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To address the paucity of clinical trial data, researchers have mined the anonymised health records of people with HIV who have used GLP-1s. This type of “observational research” has allowed researchers to study the impact and safety of GLP-1 usage among far larger groups than included in clinical trials. This research is only possible because large numbers of people with HIV are already using GLP-1s in developed countries.
Evidence from clinical and observational research suggests that these medicines provide similar levels of weight loss as when used by people without HIV.
Available evidence also suggests that GLP-1s reduce the risks of heart disease and diabetes in people living with HIV and obesity, and provide an important treatment option for metabolic-associated liver dysfunction.
Intriguingly, there is also some research suggesting that people with HIV may derive some health benefits from these medicines beyond those derived by people without HIV.
A placebo controlled study of semaglutide showed that GLP-1s may be an effective treatment for lipohypertrophy, body fat distortions associated with HIV, but the researchers cautioned that more research should be done to better understand this potential association.
Sub-studies of the lipohypertrophy trial have also suggested that GLP-1s may play a role in addressing the challenge of accelerated aging and neurocognitive decline in people with HIV. Again, more research is needed to confirm this.
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Of particular interest are the early results of a small sub-study from the clinical trial of liraglutide use in people with HIV conducted in KwaZulu-Natal. This sub-study, presented at the 2026 Conference on Retroviruses and Opportunistic Infections, looked at how GLP-1s affected the gut health of people with HIV. “The tentative results from this small study report a new potential outcome from GLP-1 drugs that might reverse and potentially mitigate early gut damage,” explains HIV advocate and science communicator Simon Collins.
Importantly, early gut damage from HIV infection is thought to be a key driver of chronic inflammation and advanced aging in people living with HIV. If GLP-1s are able to prevent or reverse gut damage, they may become a critically important health intervention for people living with HIV, says Professor Francois Venter, Director of Ezintsha. However, more research is needed to confirm this effect and to help us understand the impact of GLP-1s on the gut health of people with HIV.
Why research is needed to inform public health approaches
While several studies have provided early insights into the safety and effectiveness of GLP-1s in people with HIV, more research is needed to understand how best to use these treatments and manage their associated risks.
For example, Venter points out, we don’t know whether some GLP-1s are better for people with HIV than others, what the optimal dosing is in this population, and whether doses can be reduced over time.
It is also not known when the optimal time to start these medicines is and how the timing should be managed alongside HIV treatment initiation.
Importantly, people with HIV sometimes experience changes to their body composition known as lipohypertrophy. This often leads to the buildup of extra fat in certain parts of the body. More research is needed to understand the impact of GLP-1s on body composition in people with HIV and how these changes affect people’s body image and mental health.
In South Africa, it is important to understand whether people living with HIV want and will use these drugs and how societal perceptions of weight and HIV impact demand and adherence, explains Chandiwana.
A small clinical trial conducted among people with HIV in KwaZulu-Natal showed that GLP-1 use was highly acceptable among trial participants.
Other outstanding areas of research are operational and cost research to understand whether and how these medicines can best be provided in the public healthcare system.
As in the general population, more data is needed on the long-term effects of GLP-1 use, including its impact on bone and muscle health, and strategies to prevent bone and muscle loss. This is particularly important for people living with HIV, as HIV itself is a risk factor for both bone and muscle loss.
Why has so little clinical research been conducted?
There is significant appetite among HIV researchers to conduct more research on GLP-1 use in people living with HIV, says Venter. But conducting research in this area, he adds, has been extremely difficult to date due to the high cost of the drugs and the unwillingness of pharmaceutical companies to provide drug stock for independent research.
The good news, however, is that generic semaglutide is expected to enter the global market this year. This should result in lower drug prices and greater stock, which will make it easier to conduct critically needed research.
However, even with more affordable and available drugs, the availability of funding to conduct needed research remains a challenge says Manne-Goehler. Answering these important public health questions will require public investment, she says.
Why research is needed to inform rollout strategies
An estimated 12 million people in South Africa live with a weight-related disease. The country urgently needs new tools to curb rates of weight-related diseases and their associated treatment costs.
GLP-1s are a highly effective tool for reducing rates of obesity and weight-related diseases. Yet, trying to provide these medicines to 12 million could cripple the already overstretched and underfunded public health system.
Policy makers therefore need to understand which populations can derive the most benefit from these medicines. Given that people with HIV typically have higher risks of cardiometabolic complications than the general population, policy makers may want to consider HIV-status as one of several eligibility criteria for GLP-1 access.
“The question that… scientists and clinicians in the HIV world are really asking, [is] if our patients have an excess risk of these things happening, should we be using these medicines to treat that risk or reduce that risk differently than we use them in the general population?” says Manne-Goehler.
