The US Food and Drug Administration (FDA) this week approved Dovato, a new single-tablet antiretroviral
regimen containing the HIV integrase inhibitor dolutegravir
(sold separately as Tivicay) and the
nucleoside reverse transcriptase inhibitor lamivudine.

Dovato, from ViiV Healthcare, is the first two-drug
combination pill that provides a complete once-daily regimen for people
starting HIV treatment for the first time. ViiV’s Juluca, containing dolutegravir plus rilpivirine, is approved as a
switch option for those currently on treatment with an undetectable viral load,
but not for first-line therapy.

Other approved
integrase inhibitor-based single-tablet regimens include ViiV’s Triumeq (dolutegravir/abacavir/lamivudine),
Gilead Science’s Biktarvy
(bictegravir/tenofovir alafenamide/emtricitabine) and Gilead’s Genvoya
(elvitegravir/cobicistat/tenofovir alafenamide/emtricitabine).

Approval of Dovato was based on findings from
the phase 3 GEMINI 1 and 2 trials, which together enrolled more than 1400
participants. They were randomly assigned to receive Dovato or
dolutegravir plus tenofovir disoproxil fumarate (TDF) and emtricitabine (the
drugs in Truvada).

As
reported
at last summer’s International AIDS
Conference, 91% of Dovato recipients and 93% of
dolutegravir/TDF/emtricitabine recipients had undetectable HIV RNA at 48 weeks in
a pooled analysis of both trials. Response rates
were comparable for people who started with either low or high viral load at
baseline. Confirmed virological failure was uncommon in both treatment groups
(less than 1%) and no new drug resistance mutations were detected.

Both regimens were generally safe and
well tolerated. Dovato was associated
with fewer side-effects than the triple regimen (18% vs 24%, respectively), but
rates of withdrawal due to adverse events were the same in both groups (2%). The most common side-effects associated
with Dovato were headache, diarrhoea, nausea, insomnia and
fatigue.

Dovato avoids the potential kidney and bone problems
associated with tenofovir, especially the older TDF formulation. In
the GEMINI studies Dovato had a less
detrimental effect on serum and urine biomarkers of kidney function and markers
of bone loss. Changes in blood lipid levels were similar in both groups.

The Dovato label includes a ‘black box’
warning for people with HIV and hepatitis B virus (HBV) co-infection. Lamivudine
is active against both viruses and could lead to the development of
drug-resistant HBV and worsening liver inflammation when stopping Dovato. People with HIV/HBV co-infection
should therefore consider adding treatment for hepatitis B or choosing an
alternative HIV regimen, the label says.

Dolutegravir, one of Dovato‘s components,
has been associated with a small risk of neural tube
defects
in infants born to women who used it during early pregnancy.
Dovato should not be used at the time
of conception through the first trimester of pregnancy, according to the FDA.

Despite these
restrictions, Dovato offers a safe,
easy-to-use option for people with newly diagnosed HIV.

“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.”