Dolutegravir and Weight Gain: What the Research Really Shows

When you're managing HIV, every medication choice matters. You're not just picking a pill-you're choosing how your body will feel day after day. That’s why so many people on dolutegravir start noticing changes in their weight and wonder: is this the drug? Is it normal? Should I be worried?

What is dolutegravir?

Dolutegravir is an antiretroviral drug used to treat HIV. It belongs to a class called integrase strand transfer inhibitors (INSTIs). It works by blocking a key enzyme HIV needs to copy its genetic material into human cells. Without that step, the virus can’t spread.

It’s sold under the brand name Dolutegravir is a high-potency HIV medication that blocks viral replication by inhibiting integrase. It’s also part of combination pills like Triumeq, Dovato, and Juluca. Since its approval in 2013, it’s become one of the most prescribed HIV drugs worldwide because it’s effective, has a high barrier to resistance, and usually causes fewer side effects than older drugs.

Why does weight gain happen with HIV meds?

Weight gain isn’t unique to dolutegravir. Many people living with HIV gain weight after starting treatment-but not always for the same reasons.

Before treatment, HIV can cause chronic inflammation, loss of appetite, and muscle wasting. Once you start antiretrovirals, your immune system starts to recover. That recovery often comes with weight gain. It’s not always fat-it’s often muscle, fluid, and restored tissue. This is called immune reconstitution.

But recent studies suggest some drugs might make this gain more likely-or more extreme. That’s where dolutegravir comes in.

The research on dolutegravir and weight gain

In 2019, the TIDES study is a large clinical trial comparing dolutegravir-based regimens with other HIV treatments showed people on dolutegravir gained more weight over 96 weeks than those on efavirenz or raltegravir. The difference was clear: dolutegravir users gained an average of 4.5 kg (about 10 pounds) compared to 2.3 kg on older drugs.

Then came the ADVANCE trial is a randomized study focused on weight gain in Black women starting HIV treatment in 2020. It looked at over 1,000 people, mostly Black women, starting HIV treatment. Those on dolutegravir plus tenofovir alafenamide (TAF) gained nearly 8 kg (17.6 pounds) in two years. That’s more than double the gain seen in people on other combinations.

These weren’t flukes. A 2023 meta-analysis of 12 studies involving over 15,000 people confirmed the pattern: dolutegravir users gained more weight than those on other INSTIs like raltegravir or elvitegravir. The effect was strongest in women, Black individuals, and those with lower BMI before starting treatment.

So what’s the mechanism? Researchers think dolutegravir may affect fat cells and metabolism. Early lab studies suggest it increases the activity of enzymes that store fat and reduces how quickly the body burns energy. It might also influence appetite-regulating hormones like leptin and ghrelin.

Who’s most at risk?

Not everyone gains weight on dolutegravir. But certain groups are more likely to see significant changes:

• Women, especially Black women
• People with lower body weight before starting treatment
• Those taking dolutegravir with TAF (tenofovir alafenamide)
• People who start treatment with a low CD4 count

One study found that Black women on dolutegravir/TAF gained an average of 12% of their body weight in two years. That’s not just a few pounds-it’s a major shift in health and body image.

Is this weight gain dangerous?

Weight gain isn’t always bad. For someone who was underweight or sick from HIV, gaining weight can mean improved health. But rapid or excessive gain can raise the risk of:

• Type 2 diabetes
• High blood pressure
• Heart disease
• Fatty liver disease

Studies show that people on dolutegravir have higher rates of insulin resistance and elevated triglycerides over time-even if their cholesterol stays normal. That’s why doctors now monitor weight, waist circumference, and blood sugar more closely in people on this drug.

What should you do if you’re gaining weight?

Don’t stop your medication. Stopping HIV treatment can lead to viral rebound, drug resistance, and serious health risks.

Instead, talk to your provider. Here’s what to ask for:

1. Baseline measurements: weight, BMI, waist size, blood sugar, and lipid levels
2. Regular check-ins every 3-6 months
3. Referral to a dietitian who understands HIV and metabolic changes
4. Discussion of alternative regimens if weight gain continues

Some people switch to raltegravir, bictegravir, or even older drugs like efavirenz if weight gain becomes a problem. Switching isn’t always easy-some regimens require more pills or have different side effects-but it’s an option worth exploring.

Can lifestyle changes help?

Yes. Diet and exercise can offset some of the metabolic effects. But it’s harder than it sounds.

People on dolutegravir often report feeling hungrier, especially for carbs and sweets. That’s not weakness-it’s biology. Studies show increased ghrelin levels (the hunger hormone) in users.

Practical tips:

• Focus on protein and fiber to stay full longer
• Avoid sugary drinks and ultra-processed snacks
• Strength training helps preserve muscle and improve insulin sensitivity
• Get at least 7 hours of sleep-poor sleep worsens metabolic changes

One 2024 study found that people on dolutegravir who followed a Mediterranean-style diet and did 150 minutes of exercise weekly gained 40% less weight than those who didn’t change their habits.

What about newer drugs like bictegravir?

Bictegravir is another INSTI, similar to dolutegravir. Early data suggests it may cause less weight gain-but the evidence isn’t as strong yet. A 2025 analysis comparing the two found bictegravir users gained about 20% less weight over 12 months. But the difference wasn’t huge, and long-term data is still being collected.

So if you’re choosing a new regimen, it’s worth discussing both options. But if you’re already on dolutegravir and doing well otherwise, switching might not be necessary unless weight gain is causing health problems.

Bottom line: Is dolutegravir still a good choice?

Yes-for most people, it still is.

Dolutegravir is highly effective, easy to take (once daily, no food restrictions), and has fewer drug interactions than older meds. It’s also less likely to cause neurological side effects than efavirenz or liver toxicity than some older drugs.

The weight gain issue doesn’t mean it’s bad. It means we need to be smarter about how we use it. For someone with a low BMI and high viral load, the benefits far outweigh the risks. For someone who’s already overweight or has prediabetes, it might be worth exploring alternatives.

Bottom line: Dolutegravir isn’t the villain. But it’s not a neutral player either. It’s a powerful tool-and like any tool, it needs to be used with awareness.

What’s next?

Researchers are now looking at genetic factors that might predict who gains weight on dolutegravir. Early signs point to variations in genes linked to fat storage and insulin response. In the future, we may be able to test for those before prescribing.

For now, the message is simple: monitor, don’t panic. Talk to your doctor. Make small, sustainable changes. And remember-controlling HIV is still the top priority. Weight gain is a side effect, not a failure.