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. (Feinberg) 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. (Walmsley) The SPRING-2 study found that dolutegravir was equivalent to raltegravir in a 96-week study in previously untreated people. (Raffi)
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. (Eron)
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.
Feinberg J et al. Once-daily dolutegravir (DTG) is superior to darunavir/ ritonavir (DRV/r) in antiretroviral naive adults: 48 week results from FLAMINGO (ING114915). 53rd Interscience Conference on Antimicrobial Agents and Chemotherapy, Denver, abstract H-1464a, 2013.
Walmsley S et al. Dolutegravir (DTG; S/GSK1349572) + abacavir/lamivudine once daily statistically superior to tenofovir/emtricitabine/efavirenz: 48-week results - SINGLE (ING114467). 52nd Interscience Conference on Antimicrobial Agents and Chemotherapy, San Francisco, abstract H-556b, 2012.
Raffi F et al. Once-daily dolutegravir versus twice-daily raltegravir in antiretroviral-naive adults with HIV-1 infection (SPRING-2 study): 96 week results from a randomised, double-blind, non-inferiority trial. The Lancet Infectious Diseases, 13: 927-935, November 2013.
Eron J et al. Safety and efficacy of dolutegravir in treatment-experienced subjects with raltegravir-resistant HIV type 1 infection: 24 week results in the VIKING study. Journal of Infectious Diseases, 207: 740-748 , 2013.