Dolutegravir Drug Interactions: What You Need to Know

When you're taking dolutegravir, a potent integrase inhibitor used to treat HIV infection. It's one of the most effective HIV medications available today, often part of first-line treatment regimens. But like all drugs, it doesn't work in a vacuum—it can react with other substances in ways that reduce its power or cause harm. These reactions, called drug interactions, when two or more medications affect each other’s behavior in the body, aren't just theoretical. They can lead to treatment failure, increased side effects, or even serious health risks.

Dolutegravir is mainly processed by the liver through enzymes like UGT1A1 and CYP3A4. That means anything that affects those enzymes can change how much dolutegravir stays in your system. For example, cobicistat, a booster drug used with some HIV medications to increase their levels can raise dolutegravir concentrations too high, increasing the chance of side effects like headaches or insomnia. On the flip side, efavirenz, an older HIV drug that speeds up liver metabolism, can lower dolutegravir levels just enough to let the virus fight back. That’s why doctors avoid mixing them unless absolutely necessary—and even then, they adjust the dose.

You also need to watch out for antacids, supplements, and even some over-the-counter painkillers. Magnesium- or aluminum-containing antacids—common for heartburn—can block dolutegravir absorption if taken at the same time. The fix? Space them out by at least two hours. Calcium supplements and iron tablets? Same rule applies. Even St. John’s wort, often used for mild depression, can drop dolutegravir levels dangerously low. And while most people think of grapefruit as healthy, it doesn’t affect dolutegravir the way it does other drugs—but that doesn’t mean you should assume everything’s safe. Always check with your pharmacist before adding anything new.

This isn’t about fear—it’s about control. Knowing which drugs clash with dolutegravir lets you stay in charge of your treatment. You’re not just taking pills—you’re managing a system. That’s why the best HIV care includes regular medication reviews. Your pharmacist can spot hidden risks your doctor might miss, especially if you’re seeing multiple providers. And if you’ve ever wondered why your HIV meds come with so many warnings, now you know: it’s not bureaucracy. It’s biology.

Below, you’ll find real-world stories and science-backed insights from people who’ve navigated these interactions. Some learned the hard way. Others found simple fixes that made all the difference. Whether you’re just starting dolutegravir or have been on it for years, these articles give you the tools to ask the right questions—and avoid the pitfalls.