Dovato

Dolutegravir and lamivudine are both generally well tolerated. Side effects occurring in at least 2% of study participants receiving Dovato included headache, nausea, diarrhea, insomnia, fatigue, and dizziness. INSTIs are associated with weight gain. Dolutegravir can cause a small, reversible increase in kidney function test (serum creatinine) within the first few weeks of treatment that does not affect actual kidney function. There have been rare reports of depression and suicidal ideation with INSTIs, primarily in people with a history of psychiatric illnesses. DHHS guidelines recommend closely monitoring people with pre-existing psychiatric conditions. Prior to initiation, test for hepatitis B virus (HBV). Severe exacerbations of HBV have been reported in people with HBV co-infection who have discontinued Dovato (due to elimination of the lamivudine component, which also treats HBV). Monitor liver enzymes closely. Initiation of HBV therapy may be warranted upon Dovato discontinuation. Call your health care provider right away if you develop any of the following signs of hepatitis: yellowing of the skin or whites of the eyes; dark or tea-colored urine; pale-colored bowel movements; nausea or vomiting; loss of appetite; or pain, aching, or tenderness on the right side below the ribs.

Do not take Dovato with Epivir-HBV or the antiarrhythmic dofetilide (a heart meication). When taking carbamazepine or rifampin, take an additional dose of dolutegravir (in the form of one Tivicay tablet) 50 mg 12 hours after taking your Dovato dose. When starting or stopping dolutegravir by people on metformin, dose adjustment of metformin may be necessary to maintain optimal glycemic control or tolerability. Avoid use of sorbitol-containing medicines with lamivudine; there are many, such as acetaminophen liquid (Tylenol liquid and others). There are no known drug-drug interactions with Daklinza, Epclusa, Harvoni, Olysio, Sovaldi, Viekira Pak, or Zepatier. Not intended to be taken with other HIV medications, unless prescribed that way. Tell your provider or pharmacist about all medications, herbals, and supplements you are taking or thinking of taking, prescribed or not, as there are other drug interactions which are not listed here.

Basically, this medicine is Triumeq without the abacavir component (brand name Ziagen, also found in Epzicom). Dolutegravir is from the powerhouse drug class of integrase inhibitors, which are highly effective and generally tolerable. The benefits of using a two-drug regimen for HIV include less exposure to HIV medication while maintaining viral suppression and minimizing the potential for side effects. At one, two, and nearly three years into the GEMINI-1 and GEMINI-2 studies, DTG + 3TC was found to be non-inferior to the triple drug regimen of DTG + Truvada (emtricitabine and tenofovir DF combined in one pill). At the 144-week point, for the two studies, 82% (584 out of 716 individuals) had undetectable viral load, compared to 84% (599 out of 717) of those taking the three-drug therapy. Everyone in the study was taking HIV treatment for the first time, and 20% of them had a high viral load of more than 100,000 copies per mL when entering the clinical trials. Dovato has also been successful for treatment-experienced people switching to it after being undetectable (viral load less than 50 copies per mL). The TANGO study evaluated treatment switch from TAF-containing regimens with three or more drugs to the two-drug regimen of dolutegravir/lamivudine and, at both 48 and 96 weeks, found Dovato to be non-inferior to the three-drug regimen standard of care. Weight gain is being increasingly recognized as a side effect of INSTIs. Although dolutegravir is now a preferred medication during pregnancy as well as for people who are trying to conceive, U.S. HIV perinatal treatment guidelines suggest using three-drug regimens. Find the discussion on page C-53 of perinatal guidelines at hivinfo.nih.gov. Pregnant individuals can voluntarily enroll in the Antiretroviral Pregnancy Registry through their provider; go to apregistry.com.

Dr. Melanie Thompson:

The only two-drug regimen recommended for initial treatment, Dovato is great for many people, but shouldn’t be taken if you have hepatitis B, virus that is resistant to 3TC/FTC, or a viral load above 500,000 copies/mL. Dovato isn’t recommended for same-day treatment because a genotype, hepatitis B serology, and a viral load will not be available to guide choice of therapy. People with suppressed virus on a TAF-based regimen who have never experienced prior treatment failure and who don’t have hepatitis B may safely switch to Dovato. Weight gain with dolutegravir remains a concern, as well as the other possible INSTI side effects (insomnia and new or worsening depression). Drug interactions of note include an increase in the levels of dofetilide (which is contraindicated), metformin, and some other drugs when taken with dolutegravir. Talk with your clinician if you are taking metformin when you begin Dovato. Dolutegravir levels decrease with some seizure or tuberculosis medicines and St. John’s wort. Managing drug interactions is tricky, so be sure any clinician who is prescribing drugs for you knows all of the medicines you are taking, including over-the-counter drugs and supplements. Dolutegravir increases serum creatinine by 0.1-0.15 mg/dL within a few weeks of beginning therapy, but this is due to inhibition of creatinine secretion in the kidney rather than true kidney toxicity.

The price of Dovato (monthly wholesale acquisition cost of $2,652) is over $641 higher than the price of Tivicay alone, representing quite an inflated price for a month of generic 3TC whose wholesale acquisition cost is as low as $75/month. For more information on dolutegravir, see Tivicay.

Activist Joey Wynn:

Some folks are looking to take fewer medications; a 2-drug combo could be for you if that is your priority.

This combo is still a hard “no” for anyone on metformin for diabetes or on TB therapy, unless you take an extra dolutegravir pill to compensate for the interaction.

Overall, this is a good choice, and very underrated; talk to your provider to see if this is right for you, especially if you’re wanting to reduce the medications you’re taking.