Dovato is a two-drug combination of the HIV integrase inhibitor dolutegravir (also in Tivicay, Triumeq) and the HIV nucleoside reverse transcriptase inhibitor lamivudine (also in Epivir, Kivexa, Triumeq).
It combines 50mg of dolutegravir and 300mg of lamivudine in a white tablet with 'SV 137' on one side.
Dovato was approved for use by previously untreated adults in the United States in March 2019 and in the European Union in July 2019. Dovato can be used without other HIV medications as a complete treatment combination.
Approval was granted on the basis of results from the phase 3 GEMINI 1 & 2 studies. The studies randomised 1441 previously untreated people with HIV to receive either dolutegravir/lamivudine or dolutegravir/tenofovir disoproxil fumarate/emtricitabine for 48 weeks. Pooled analysis of the two studies showed that 91% in the two-drug arm and 93% in the three-drug arm had a viral load below 50 copies/ml at week 48, indicating that the two-drug regimen was non-inferior to the three-drug regimen. Fewer participants in the two-drug arm experienced adverse events than in the three-drug arm (18% vs 24%).
Ninety-six-week follow-up of the GEMINI 1 & 2 studies showed that viral suppression in the two-drug arm was sustained. 86.0% in the dolutegravir/lamivudine group and 89.5% in the dolutegravir/tenofovir disoproxil fumarate/emtricitabine group had continued viral suppression below 50 copies at week 96). Eleven people in the two-drug group and seven in the three-drug group withdrew from the study due to virological failure, none of whom developed treatment-emergent resistance.
Dovato has also been tested as a switch option in people who already have fully suppressed viral load. In the TANGO-1 study. In order to be eligible, study participants were required to have no history of treatment failure or evidence of resistance to the study drugs.
The study randomised 741 people with viral load below 50 copies/ml to continue an existing three-drug regimen containing tenofovir alafenamide (TAF) and emtricitabine or to switch to dolutegravir/lamivudine. Eighty per cent of study participants were taking an integrase inhibitor at study entry, predominantly cobicistat-boosted elvitegravir (the Genvoya single-tablet regimen contains elvitegravir/cobicistat/TAF/emtricitabine).
In the primary analysis at 48 weeks, 93.2% of people who switched to dolutegravir/lamivudine and 93.0% of those who stay on their current regimen achieved viral suppression, again meeting the criteria for non-inferiority. Zero participants in the switch group and two in the TAF-based regimen group experienced virologic treatment failure.
Moderate to severe drug-related adverse events occurred more frequently in the dolutegravir/lamivudine arm (6% vs < 1%). Nine people in the two-drug arm and one person in the three-drug arm discontinued their assigned treatment due to drug-related adverse events.
Dovato is taken once daily, with or without food.
Antacids containing magnesium should be taken at least 6 hours before or 2 hours after Dovato.
Calcium supplements, iron supplements or multivitamins should be taken at the same time as Dovato, with a meal.
Common side effects of Dovato include:
- Headache, dizziness, drowsiness, tiredness
- Depression, anxiety, difficulty in sleeping, abnormal dreams
- Nausea, diarrhoea, abdominal pain, vomiting, flatulence
- Increased liver enzymes or creatinine phosphokinase
- Rash, itching, hair loss
- Muscle and joint pains.
You should not take Dovato if you are currently taking medicines from the following groups:
- Cladribine (chemotherapy)
- Medicines containing sorbitol, xylitol, mannol, lactitol, maltitol (agents used as fillers in some liquid medicines).
An analysis of eight clinical trials of new drugs introduced after 2003 found that weight gain was significantly greater in people taking an integrase inhibitor and that dolutegravir or bictegravir were associated with a higher risk of substantial weight gain (> 10% of body mass) than other drugs of this type. (Sax 2019) Weight gain may be increased when dolutegravir is combined with tenofovir alafenamide (TAF) but the TANGO study found no significant difference in weight gain after 48 weeks between participants randomised to Dovato or to dolutegravir, emtricitabine and TAF. (Van Wyk)
If Dovato is used with St John’s wort, the tuberculosis treatment rifampicin or the anticonvulsants carbamazepine, phenobarbital, phenytoin or oxcarbazepine, an additional 50mg tablet of dolutegravir should be taken 12 hours after Dovato.
Dovato is not associated with a higher risk of virological failure or development of drug resistance compared to a three-drug regimen containing dolutegravir. See Dolutegravir for further information on resistance to dolutegravir.
Dovato is not recommended for women who might become pregnant or in the first three months of pregnancy. Dovato should be used with effective contraception.
The safety and efficacy of Dovato has not been tested in children under the age of 12. Dovato is not approved for children under 12 years in the European Union. Dovato is not approved for people under 18 years in the United States.
Cahn P et al. Dolutegravir plus lamivudine versus dolutegravir plus tenofovir disoproxil fumarate and emtricitabine in antiretroviral-naive adults with HIV-1 infection (GEMINI-1 and GEMINI-2): week 48 results from two multicentre, double-blind, randomised, non-inferiority, phase 3 trials. The Lancet, 393: 143-155, 2019.
Cahn P et al. Durable efficacy of dolutegravir (DTG) plus lamivudine (3TC) in antiretroviral treatment-naïve adults with HIV-1 infection - 96-week results from the GEMINI studies. 10th International AIDS Society Conference on HIV Science, Mexico City, abstract WEAB0404LB, 2019.
Van Wyk J et al. Switching to DTG+3TC fixed dose combination (FDC) is non-inferior to continuing a TAF-based regimen (TBR) in maintaining virologic suppression through 24 weeks (TANGO study). 10th International AIDS Society Conference on HIV Science, Mexico City, abstract WEAB0403LB, 2019.
Van Wyk J et al. Efficacy and safety of switching to dolutegravir/lamivudine fixed-dose 2-drug regimen vs continuing a tenofovir alafenamide–based 3- or 4-drug regimen for maintenance of virologic suppression in adults living with Human Immunodeficiency Virus type 1: phase 3, randomized, noninferiority TANGO study. Clinical Infectious Diseases, 71: 1920-29, 2020.