Combination therapy of lamivudine plus dolutegravir has demonstrated satisfactory efficacy, safety, and tolerability in providing antiviral treatment to individuals with HIV-1 infection, according to a study recently published in The Lancet.
This research was composed of 2 multicenter, randomized, double-blind studies (GEMINI-1 [NCT02831673 on ClinicalTrials.gov] and GEMINI-2 [NCT02831764]) and included 1441 individuals with HIV-1. These participants were randomly assigned to either a daily 2-drug regimen (dolutegravir 50 mg and lamivudine 300 mg; n=719) or a daily 3-drug regimen (dolutegravir 50 mg, tenofovir disoproxil fumarate 300 mg, and emtricitabine 200 mg; n=722). In the GEMINI-1 study, 90% of those in the 2-drug group and 93% of those in the 3-drug group (adjusted treatment difference, -2.6%; 95% CI, -6.7% to 1.5%) achieved less than 50 copies per mL of HIV-1 RNA. In the GEMINI-2 study, 93% of those in the 2-drug group and 94% of those in the 3-drug group (adjusted treatment difference, -0.7%; 95% CI, -4.3% to 2.9%) achieved these levels, respectively. This indicated a -10% margin of non-inferiority across the 2 studies.
Headache, nasopharyngitis, nausea, insomnia, infection of the upper respiratory tract, and diarrhea comprised the most common set of reported adverse events. Treatment-related adverse events were more common among those on the 3-drug regimen (24%) than the 2-drug regimen (18%), and only 2% discontinued treatment due to adverse events in either group. There were 2 cases of mortality in the GEMINI-2 study, but both were determined to be unrelated to treatment.
The 2 phase-3 studies comprising this research were identical in design and took place from July 2016 through March 2017 in 21 countries. Participants were at least age 18 years, were antiretroviral therapy-naive, and had HIV-1 RNA levels of ≤500,000 copies per mL. Participants were masked as to which treatment they received, and both the 2- and 3-drug regimens were taken orally. Week 48 HIV-1 RNA levels of fewer than 50 copies per mL were the primary outcome.
The study researchers concluded that “the two-drug regimen of dolutegravir plus lamivudine provides high antiviral potency with a high barrier to resistance and favorable safety and tolerability profiles. The GEMINI studies provide strong data supporting dolutegravir plus lamivudine as an effective, well-tolerated option for treatment of patients with HIV-1 infection.”
This study received funding from the pharmaceutical company ViiV Healthcare, which played a role in writing and designing the study as well as in collecting and interpreting data.
Cahn P, Madero JS, Arribas JR, et al. Dolutegravir plus lamivudine versus dolutegravir plus tenofovir disoproxil fumarate and emtricitabine in antiretroviral-naive adults with HIV-1 infection (GEMINI-1 and GEMINI-2): week 48 results from two multicentre, double-blind, randomised, non-inferiority, phase 3 trials [published online November 9, 2018]. Lancet. doi: 10.1016/S0140-6736(18)32462-0