Weighing the Benefits of 2-ART Vs 3-ART Combinations

One area of focus within HIV care in recent years has been polypharmacy. The concept of getting people with HIV (PWH) to decrease the number of antiretroviral therapies (ART) is appealing in helping to ease the burden associated with it.

In thinking about this, ViiV Healthcare has developed its 2-medication combination, Dovato (dolutegravir/lamivudine), a once daily, oral ART which was approved by the US Food and Drug Administration (FDA) in April of 2019, and is indicated as a complete regimen to treat HIV infection in adults with no ART treatment history or to replace the current ART regimen in those who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable ART regimen with no history of treatment failure and no known resistance to any component to the therapy. Dolutegravir is an integrase inhibitor and lamivudine is a reverse transcriptase inhibitor.

In recent months, the company released data from its GEMINI study program around this ART.

GEMINI 1 and GEMINI 2 were duplicate, phase 3, randomized, double-blind, multicenter, parallel group, non-inferiority studies. These studies evaluate a 2-drug regimen of dolutegravir plus lamivudine compared with a 3-drug regimen of dolutegravir plus TDF/FTC in HIV infected, antiretroviral treatment-naïve adult participants with baseline HIV viral loads between 1000 and 500000 c/mL. The studies were performed at 192 centers in 21 countries.

Results from GEMINI confirmed dolutegravir plus lamivudine’s long-term viral suppression was non-inferior to the 3-drug regimen.

“These long-term data confirm that dolutegravir-based 2-drug regimens have a rightful place in the HIV treatment compendium,” Pedro Cahn, MD, scientific director, Fundación Huésped, professor of Infectious Diseases, Buenos Aires University Medical School, was a principal investigator for the GEMINI study program, said. “Dolutegravir plus lamivudine continues to demonstrate long-term non-inferior efficacy compared to dolutegravir plus TDF/FTC with benefits beyond viral suppression.”

He pointed out that as young PWH will have lifetime ART treatment, the idea of one less therapy is appealing. “A young person in his 20s has to be on treatment [potentially] for the next 50 to 60 years, so exposing a patient unnecessarily to a third drug is the wrong choice,” Cahn stated. 

And for those patients who fit the criteria, and might consider a switch in their regimen from a 3-drug to a 2-drug regimen, Cahn would not have any reservations. 

One area of concern associated with ART has been weight gain and the potential for insulin resistance. Cahn noted that after 144 weeks they saw an average of 3.4 kilograms.

Cahn also offered some guidance about patients with hepatitis B (HBV) with regards to the therapy in the trials.

“If a patient is coinfected with hepatitis B, they should not be included,” Cahan stated.

Specifically one of the medications, lamivudine, has been problematic to people in this patient population.

“Emergence of lamivudine-resistant HBV variants associated with lamivudine-containing antiretroviral regimens has been reported. If Dovato is used in patients co-infected with HIV-1 and HBV, additional treatment should be considered for appropriate treatment of chronic HBV; otherwise, consider an alternative regimen,” is the warning the company has published on its website.

Cahn spoke to Contagion® about the trial results, its side effects profile, and its potential place in HIV care.