Dolutegravir
(Tivicay) belongs to the class of antiretroviral drugs known as
integrase inhibitors. The drug works against HIV's integrase protein,
blocking its ability to integrate its genetic code into human cells.
It was
given marketing approval by the Food and Drug Administration (FDA) in the US in
2013 and in Europe in January 2014 for use by adults and adolescents over 12
years of age.
Dolutegravir
is formulated as a yellow 50mg tablet. The dose of dolutegravir is 50mg (one tablet)
once a day, or twice a day if taken with efavirenz, nevirapine, tipranavir, or
for HIV known to be resistant to integrase inhibitors. It can be taken with our
without food.
Dolutegravir
is also available as part of a fixed-dose combination pill called Triumeq. See Triumeq
for further details.
Clinical
trials leading to the approval of dolutegravir show that three-drug regimens
containing the drug are highly effective and well tolerated. Several studies
have shown that dolutegravir-based treatment is superior to treatment
containing either darunavir/ritonavir or efavirenz in previously untreated
people. The FLAMINGO study showed that dolutegravir plus two nucleoside
reverse transcriptase inhibitors (NRTIs) was superior to darunavir/ritonavir (90% vs 83% virally
suppressed after 48 weeks), especially in people with high viral loads.1 The
SINGLE study compared dolutegravir/abacavir/lamivudine
to Atripla. Here again,
dolutegravir-based treatment was superior (88% vs 81% virally suppressed at 48
weeks) due to fewer side-effects leading to treatment discontinuation.2
The SPRING-2 study found that dolutegravir was equivalent to raltegravir in a
96-week study in previously untreated people.3
Due
to its high potency and good tolerability dolutegravir is recommended as a
preferred element of first-line treatment in British HIV Association, US and
European AIDS Clinical Society treatment guidelines.
Due
to its lack of cross-resistance to raltegravir, dolutegravir is highly
effective in suppressing viral load in people with raltegravir treatment
failure, especially when dosed twice daily and combined with at least one other
active drug.4
Dolutegravir
is also being tested in clinical trials as part of a two-drug therapy in
combination with either lamivudine or rilpivirine. Trials show that
dolutegravir is just as effective when combined with one of these drugs as when
used in a three-drug combination, at least for people who already have fully
suppressed viral load. The advantage of using dolutegravir in a two-drug
combination is that it may reduce the risk of long-term side-effects.
Important
warning: An
allergic (hypersensitivity) reaction has been reported in some people taking
dolutegravir. This is not common, but you should see a doctor immediately if
you think you are experiencing an allergic reaction. The symptoms are skin
rash; fever; fatigue; swelling, sometimes of the face or mouth, causing
breathing problems; muscle or joint aches.
Common
side-effects experienced by people taking dolutegravir include: nausea,
diarrhoea, headache, rash, itching, vomiting, stomach pain or discomfort,
abnormal dreams, fatigue, flatulence, increase in liver enzymes, increase in
creatine phosphokinase (enzymes produced in the muscles). People taking
dolutegravir may also be at higher risk of some central nervous system side-effects,
most commonly insomnia, dizziness and headache. These side-effects may be more
common in women, in people who take the drug combined with abacavir and in
people over 60 years of age.
Rare
side-effects include allergic reaction, and liver inflammation.
It is
very important to tell your prescribing doctor about any drugs you are taking,
whether they are prescribed by another doctor, bought from a pharmacy, or
herbal, recreational, or other drugs. There are some key drug interactions for
dolutegravir, but your doctor or pharmacist should check for other interactions
too. Do not take dolutegravir with dofetilide, a drug used to treat certain
heart conditions. You should not take antacids (used to treat indigestion and
heartburn), calcium supplements, iron supplements or multivitamins for six
hours before you take dolutegravir, or for at least two hours after taking
dolutegravir. Dolutegravir also interacts with other drugs, which may mean you
need to adjust the dose you take, or need closer monitoring from your doctor.
This includes metformin, rifampicin, some epilepsy drugs, and St John’s wort.