Researchers in South Africa followed 367 people with HIV who started taking a new combination medicine called TLD. After 48 weeks, about 18% of participants gained a significant amount of weight. The study looked at whether eating habits and exercise could explain this weight gain. Surprisingly, the researchers found that diet and physical activity didn’t strongly predict who would gain weight. This suggests that the medicine itself, rather than lifestyle choices, may be the main reason for weight gain in people taking this medication. The findings could help doctors and patients understand that weight gain might be a side effect they need to manage differently.

The Quick Take

  • What they studied: Whether eating habits and exercise explain why people with HIV gain weight when starting a new medication combination called TLD
  • Who participated: 367 people with HIV in South Africa, with an average age of 42 years; about 78% were women; all were starting the same HIV medication for the first time
  • Key finding: About 1 in 5 people (18%) gained a significant amount of weight (10% or more of their starting weight) over 48 weeks, but this weight gain was not strongly connected to what they ate or how much they exercised
  • What it means for you: If you’re taking this HIV medication and gaining weight, it’s likely due to the medicine itself rather than eating too much or not exercising enough. This means doctors may need to develop different strategies to help manage weight gain, rather than just telling patients to diet and exercise more.

The Research Details

This was a real-world observation study, not an experiment. Researchers followed 367 people with HIV in South Africa who were starting a new three-drug combination called TLD (which includes dolutegravir, tenofovir, and lamivudine). They tracked these people for 48 weeks (about 11 months) and measured their weight at the beginning and end. They also asked detailed questions about what people ate (fruits, vegetables, fast food, fried foods, sugary drinks) and how much physical activity they did. The researchers compared the eating and exercise habits of people who gained significant weight (10% or more) to those who didn’t gain much weight.

Understanding whether lifestyle causes weight gain is important because it tells doctors whether to focus on helping patients change their habits or whether they need to look at the medicine itself. If weight gain is mainly caused by the medicine, then diet and exercise advice alone won’t solve the problem, and doctors need different approaches.

This study has several strengths: it followed real patients in their actual lives (not a controlled lab setting), it had a decent number of participants (367), and it measured multiple lifestyle factors. However, it’s observational, meaning researchers watched what happened rather than randomly assigning people to different diets or exercise programs. The study also relied on people remembering and reporting what they ate, which can be inaccurate. The results show that lifestyle factors weren’t strongly connected to weight gain, but this doesn’t prove the medicine caused it—other factors could be involved.

What the Results Show

Among the 367 participants, 18% (about 66 people) experienced clinically significant weight gain, defined as gaining 10% or more of their starting body weight over 48 weeks. When researchers compared people who gained significant weight to those who didn’t, they found only one dietary difference: people who gained weight actually increased their fruit intake slightly more than those who didn’t gain weight. This was unexpected and counterintuitive. Importantly, there were no significant differences in vegetable intake, fast food consumption, fried food consumption, sugar-sweetened beverage intake, or physical activity levels between the two groups. When researchers used statistical models to look at all these factors together, none of them predicted who would gain weight.

The study found that the average changes in most lifestyle behaviors were similar between people who gained weight and those who didn’t. Vegetable intake, fast food frequency, fried food frequency, and physical activity all showed no meaningful differences between groups. The only notable finding was the unexpected increase in fruit intake among weight gainers, which the researchers noted was surprising and doesn’t have an obvious explanation. This lack of lifestyle differences across the board strengthens the conclusion that something other than diet and exercise is driving the weight gain.

Previous research has shown that people with HIV often gain weight when starting certain medications, particularly ones containing dolutegravir. This study adds important information by showing that lifestyle factors don’t explain this weight gain as much as doctors might have assumed. Other research has suggested that HIV medications can affect how the body stores fat and regulates appetite at a biological level, which would explain why lifestyle changes alone don’t prevent the weight gain.

The study has several important limitations. First, it relied on people self-reporting what they ate and how much they exercised, which is often inaccurate. Second, the study only lasted 48 weeks, so we don’t know if patterns change over longer periods. Third, the study didn’t measure other factors that could affect weight gain, such as hormonal changes, changes in metabolism, or how the medicine affects appetite and fat storage. Fourth, the study was observational, so researchers couldn’t prove that the medicine caused the weight gain—only that lifestyle factors didn’t explain it. Finally, all participants were from South Africa, so results might not apply to people in other countries with different diets and lifestyles.

The Bottom Line

If you’re taking this HIV medication and gaining weight, understand that diet and exercise alone may not prevent this side effect. Work with your doctor to monitor your weight and discuss strategies beyond lifestyle changes, which might include switching medications if weight gain becomes a serious problem, or managing weight through medical interventions. Continue healthy eating and exercise for overall health benefits, but don’t blame yourself if weight gain occurs despite your efforts. (Confidence: Moderate—based on one study in one region)

This research is most relevant to people with HIV taking or considering TLD medication, their doctors and healthcare providers, and HIV treatment programs in sub-Saharan Africa. People taking other HIV medications should note that weight gain patterns may differ. This is less relevant to people without HIV or those taking different medications.

Weight gain appeared to happen gradually over the 48-week study period, with about 18% of people experiencing significant weight gain. Most people likely wouldn’t notice major changes in the first few weeks, but weight gain could become noticeable within 3-6 months of starting the medication.

Want to Apply This Research?

  • Track weekly weight measurements and note the date you started TLD medication. Record weight at the same time each week (e.g., every Monday morning before eating) to identify trends. Set a baseline weight at medication start and monitor for 10% increases, which would indicate clinically significant weight gain.
  • While diet and exercise may not prevent medication-related weight gain, use the app to maintain healthy habits for overall wellness: log daily fruit and vegetable servings (aim for variety), track physical activity minutes (aim for 150 minutes moderate activity per week), and monitor water intake instead of sugary drinks. These habits support general health even if they don’t prevent medication-related weight gain.
  • Create a long-term weight tracking dashboard that shows your weight trend over months. Set monthly check-in reminders to review progress with your healthcare provider. If you notice consistent weight gain despite healthy lifestyle habits, use the app to document this and discuss with your doctor about potential medication adjustments or additional interventions.

This research describes what happened in one study of 367 people in South Africa and should not replace medical advice from your healthcare provider. If you’re taking HIV medication and experiencing weight gain, discuss your concerns with your doctor—they can evaluate your individual situation, consider your specific medications, and recommend the best approach for you. Weight gain can have health implications, and your doctor may suggest monitoring, medication changes, or other interventions based on your personal health needs. This article is for educational purposes and is not medical advice.