FDA Approves Dolutegravir/Lamivudine for Treatment-Naive Patients With HIV

The US Food and Drug Administration (FDA) has issued an approval for dolutegravir and lamivudine (Dovato), as a complete regimen for treatment-naïve adults with HIV-1.

This marks the first FDA-approved 2-drug, fixed-dose, complete regimen for treatment-naïve adults with HIV, according to the press release.

"Currently, the standard of care for patients who have never been treated is a three-drug regimen. With this approval, patients who have never been treated have the option of taking a two-drug regimen in a single tablet while eliminating additional toxicity and potential drug interactions from a third drug," Debra Birnkrant, MD, director of the Division of Antiviral Products, said in the statement. "Having a drug-sparing treatment available that uses fewer drugs is beneficial to patients who may have issues taking multiple medications over a long period of time."

The efficacy and safety of dolutegravir/lamivudine as a once-daily tablet were demonstrated in 2 identical, randomized, double-blind, controlled clinical trials, GEMINI 1 and 2. A total of 1433 adults with no prior antiretroviral treatment history were included. The trials showed that the regimen had a similar effect of reducing the amount of HIV in the blood when compared with a regimen of dolutegravir, emtricitabine, and tenofovir. The treatment was considered successful if the patient maintained low-levels (less than 50 copies/mL) of HIV RNA in their blood for at least 48 weeks.

The results are consistent for the suppression of HIV across individuals with higher viral loads (>100,000 c/mL) and lower viral loads (<=100,000 c/mL). In a pooled analysis, 81% of patients taking dolutegravir and lamivudine had HIV RNA <50 c/mL compared with 93% of patients taking dolutegravir, emtricitabine, and tenofovir.

Two-percent of patients in each study arm withdrew because of adverse events, the most common of which being headache, diarrhea, and nasopharyngitis (dolutegravir/lamivudine arm: 10%, 9%, and 8%, respectively, dolutegravir, emtricitabine, and tenofovir: 10%, 11%, and 11%, respectively). Adverse events were less frequent in patients on the dolutegravir/lamivudine regimen (18%) compared with those on dolutegravir, emtricitabine, and tenofovir regimen (24%).

None of the patients who experienced virologic failure in either treatment arm developed treatment-emergent resistance, according to the statement.

The labeling for dolutegravir/lamivudine includes a Boxed Warning, cautioning that patients with HIV and hepatitis B should add additional treatment for their hepatitis B or consider a different drug regimen. Patients have developed hepatitis B variants associated with resistance to lamivudine and may have severe liver problems, including liver failure, when they stop taking drugs containing lamivudine. Patients with both HIV and hepatitis B virus who stop using Dovato should be closely monitored by their health care provider.

Other common adverse reactions with dolutegraivir/lamivudine were headache, diarrhea, nausea, insomnia and fatigue. As there is a known risk for neural tube defects with dolutegravir, patients are advised to avoid use of dolutegravir/lamivudine at the time of conception through the first trimester of pregnancy.

In Feburary, Contagion® spoke with Paul Edward Sax, MD, professor of medicine at Harvard Medical School and clinical director of the Division of Infectious Diseases at Brigham and Women’s Hospital, about the 2-drug regimen.

“Dolutegravir lamivudine is another interesting concept for treating HIV both as initial therapy and also for people who have viral suppression," he said. "So, a 2-drug approach to treating HIV could potentially offer benefits in safety—because you're not exposing people to as many drugs&mdash;as well as in cost. And so, we've done some work modeling showing that 2-drug treatment with dolutegravir and lamivudine is likely to be highly cost-effective for both people starting therapy and for people who are already successfully treated.”