FDA Approves Dolutegravir/Lamivudine for Treatment-Naive Patients With HIV
Dolutegravir/lamivudine (Dovato) becomes the first 2-drug, fixed-dose complete treatment 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—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.”