General Information

Dovato is specifically indicated as a complete regimen for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults with no antiretroviral treatment history or to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral regimen with no history of treatment failure and no known substitutions associated with resistance to the individual components of Dovato.

Dovato is supplied as a tablet for oral administration. Dovato is a fixed-dose combination product containing 50 mg of dolutegravir and 300 mg of lamivudine. The recommended dosage regimen in adults is one tablet taken orally once daily with or without food.

The dolutegravir dose (50 mg) in Dovato is insufficient when co-administered with drugs listed below that may decrease dolutegravir concentrations; the following dolutegravir dosage regimen is recommended:

Co-administered Drug: Carbamazepine, rifampin

Dosing Recommendation: An additional dolutegravir 50-mg tablet, separated by 12 hours from Dovato, should be taken.

Dovato is not recommended in patients with renal impairment or severe hepatic impairment.

Mechanism of Action

Dovato is a once-daily, single-tablet, two-drug regimen that combines the integrase strand transfer inhibitor (INSTI) dolutegravir (Tivicay, 50 mg) with the nucleoside analogue reverse transcriptase inhibitor (NRTI) lamivudine (Epivir, 300 mg). Dovato uses these two drugs to inhibit the viral cycle at two different sites. INSTIs, like dolutegravir, inhibit HIV replication by preventing the viral DNA from integrating into the genetic material of human immune cells (T-cells). This step is essential in the HIV replication cycle and is also responsible for establishing chronic infection. Lamivudine is an NRTI that works by interfering with the conversion of viral RNA into DNA which in turn stops the virus from multiplying.

Side Effects

Adverse effects associated with the use of Dovato may include, but are not limited to, the following:

headache

diarrhea

nausea

insomnia

fatigue

The Dovato drug label comes with the following Black Box Warning: All patients with HIV-1 should be tested for the presence of HBV prior to or when initiating Dovato. Emergence of lamivudine-resistant HBV variants associated with lamivudine-containing antiretroviral regimens has been reported. If Dovato is used in patients co-infected with HIV-1 and HBV, additional treatment should be considered for appropriate treatment of chronic HBV; otherwise, consider an alternative regimen. Severe acute exacerbations of HBV have been reported in patients who are co-infected with HIV-1 and HBV and have discontinued lamivudine, a component of Dovato. Closely monitor hepatic function in these patients and, if appropriate, initiate anti-HBV treatment.

Clinical Trial Results

ART Naive Patients

The FDA approval of Dovato was based on GEMINI 1 (204861) and GEMINI 2 (205543) duplicate, Phase III, randomized, double-blind, multicenter, parallel group, non-inferiority studies. These studies evaluated a two-drug regimen of dolutegravir and lamivudine compared with a three-drug, first-line regimen of DTG + TDF/FTC in HIV-1 infected, antiretroviral therapy (ART)-naïve adult participants with baseline HIV-1 viral loads up to 500,000 copies per milliliter. The trials were designed to study the efficacy and safety of once-daily dolutegravir and lamivudine compared to once-daily dolutegravir and the fixed-dose combination of TDF/FTC at 48 weeks in more than 1,400 HIV-1-infected, ART-naïve adult participants. In these studies, DTG + 3TC demonstrated non-inferiority based on plasma HIV-1 RNA <50 copies per milliliter (c/mL), a standard measure of HIV-1 control, at Week 48 when compared to a three-drug regimen of DTG and two nucleoside reverse transcriptase inhibitors (NRTIs), tenofovir disoproxil fumarate/emtricitabine (TDF/FTC), in treatment-naïve, HIV-1 infected adults.

ART-Experienced Patients

The FDA approval of Dovato as a complete regimen for the treatment of HIV-1 infection to replace the current antiretroviral (ARV) regimen in adults who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable ARV regimen with no history of treatment failure and no known resistance to the individual components of Dovato was based on the phase III TANGO study. This study demonstrated adults living with HIV-1, who had maintained virologic suppression for at least six months on a TAF-containing regimen of at least three drugs, were able to maintain similar rates of virologic suppression after switching to Dovato, compared with those who continued the original regimen. No participants on Dovato and one participant (<1%) on the TAF-containing regimen met confirmed virologic failure criteria, with no resistance mutations observed at failure.