The U.S. Food and Drug Administration this week approved Dovato, a two-drug combination pill that provides a complete once-daily antiretroviral regimen for people starting HIV treatment for the first time. Dovato, from ViiV Healthcare, contains the HIV integrase inhibitor dolutegravir (sold separately as Tivicay) plus the nucleoside reverse transcriptase inhibitor lamivudine.
"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," said Dr. Debra Birnkrant, director of the FDA's Division of Antiviral Products. "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."
Dovato is the first dual-drug single-tablet regimen approved for previously untreated people with HIV. ViiV's earlier two-drug combo pill containing dolutegravir plus rilpivirine, sold as Juluca, is only approved for those currently on treatment with an undetectable viral load who want to switch to a simpler regimen. Dovato is expected to sell for about $2,300 per month, according to ViiV.
FDA approval of Dovato was based on findings from a pair of Phase 3 clinical trials that compared the two medications in the combination pill against a standard three-drug regimen of dolutegravir plus tenofovir disoproxil fumarate and emtricitabine (the drugs in Truvada) for first-time treatment.
The studies, which together enrolled more than 1,400 people, showed that both regimens led to a high rate of viral suppression after a year on treatment (91 percent versus 93 percent, respectively). Treatment failures were uncommon in both treatment groups and no new drug resistance was seen.
Treatment was generally well tolerated. The most common side effects were headache, diarrhea, nausea, insomnia, and fatigue. Only 2 percent of people taking either regimen stopped treatment because of side effects.
"For the last 15-20 years, the standard of care for HIV has revolved around three-drug regimens. Now that we have more potent drugs, the focus is shifting to tolerability and convenience," lead study investigator Dr. Pedro Cahn said when he presented the findings last summer at the International AIDS Conference in Amsterdam. "The GEMINI studies show that we can get the efficacy of three drugs in a two-drug regimen with the tolerability and drug interaction profile of [dolutegravir] and [lamivudine]."
The lamivudine in Dovato is active against hepatitis B virus as well as HIV. Experts said that people with both viruses should take additional medications for hepatitis B because they could develop drug-resistant HBV and experience worsening liver problems when they stop Dovato. The dolutegravir in Dovato has been associated with a very small risk of neural tube birth defects in infants born to women who used it during early pregnancy. The FDA said that Dovato should not be used at the time of conception through the first trimester of pregnancy.
Advocates said that Dovato offers a safe, easy-to-use option for people with newly diagnosed HIV who face a lifetime of treatment. In particular, it avoids the potential kidney and bone problems associated with tenofovir, an ingredient in several other available single-tablet regimens.
"The approval of Dovato is a welcome paradigm shift, as it brings an innovative treatment approach to newly diagnosed adults with HIV," said longtime advocate Jeff Berry of the Test Positive Aware Network. "By exposing patients to fewer drugs at the start of treatment, the hope is to help address concerns arising from overall management of prolonged antiretroviral therapy."