Week 96 GEMINI Results Reinforce Efficacy of DTG/3TC

GEMINI 1 & 2 are phase 3, randomized, double-blind, multicenter studies evaluating the 2-drug regimen of DTG/3TC in comparison with the 3-drug regimen of DTG + TDF/FTC.

New results from the GEMINI studies demonstrate the continued non-inferior efficacy of dolutegravir + lamivudine (DTG/3TC) compared with a regimen DTG plus tenofovir disoproxil fumarate/emtricitabine (TDF/FTC).

GEMINI 1 & 2 are phase 3, randomized, double-blind, multicenter studies evaluating the 2-drug regimen of DTG/3TC in comparison with the 3-drug regimen of DTG + TDF/FTC among individuals with HIV-1 who are antiretroviral treatment naïve and have baseline HIV-1 viral loads up to 500,000 c/mL.

The week 96 results of the parallel studies were presented at the 10th IAS Conference on HIV Science (IAS 2019) and reinforce the non-inferiority between the regimens that was established in the week 48 results.

At week 96, a pooled analysis of the 2 studies showed that 616 of the 716 (86%) participants in the DTG/3TC arm had HIV-1 RNA <50 copies per milliliter compared with 642 of the 717 (90%) participants in the DTG + TDF/FTC arm [adjusted difference -3.4 (-6.7, 0.0)].

Across both studies, 11 participants (1.5%) on DTG/3TC and 7 (1.0%) on DTG + TDF/FTC met protocol-defined virologic withdrawal criteria. However, no patient who experienced confirmed virologic withdrawal in either treatment arm developed treatment-emergent resistance.

Pooled results indicate that response rates from viral suppression in participants with a baseline viral load of more than 100,000 copies of viral RNA per m/L of blood plasma (>100,000 c/mL) were similar between the DTG/3TC group and the DTG + TDF/FTC arm (GEMINI 1: 81% (60/74) compared with 88% (67/76) in the respective arms [unadjusted difference -7.1 (-18.6,4.4)]; GEMINI 2: 86% (57/66) compared with 84% (65/77) in the respective arms [unadjusted difference 1.9 (-9.6,13.5)]).

Additionally, the studies found that the response rate remained lower in DTG/3TC participants with CD4+ < 200 cells/mm3 (GEMINI 1: 65% (20/31) compared with 90% (26/29) in the respective arms [unadjusted difference -25.1 (-45.3,-5.0)] GEMINI 2: 72% (23/32 compared with 85% (22/26) [unadjusted difference -12.7 (-33.6,8.1)] in the respective arms), which was consistent with the findings in the week 48 results.

The most common drug-related adverse events from the pooled results were nasopharyngitis, diarrhea, and headache in both arms, (DTG/3TC 10%, 12%, and 11% respectively, DTG + TDF/FTC 16%, 13%, and 12%, respectively).

It was also observed that drug-related adverse events occurred less frequently in participants on the DTG/3TC arms compared with those in the DTG + TDF/FTC arms (140 of 716 participants, [20%] vs 179 of 717 participants [25%] respectively).

The rates of serious adverse events were comparable (64 of 716 participants [9%] vs 67 of 717 participants [9%] in the DTG/3TC arms versus the DTG + TDF/FTC arms) and 3% of participants withdrew due to adverse events in each study arm.

“The week 96 data from the GEMINI studies demonstrate that the clinical benefits of dolutegravir plus lamivudine we saw at week 48 are sustainable, allowing us to use these 2 drugs while still getting efficacy non-inferior to that of a dolutegravir-based 3-drug regimen,” Pedro Cahn, MD, principal investigator for the GEMINI study program, said in a press release issued by ViiV Healthcare. “This provides further evidence for the benefits of this dolutegravir-based 2-drug regimen in a treatment-naïve population, and enables physicians and people living with HIV to be confident in the durability of this treatment option.”

According to the abstract, GEMINI 1 & 2 will continue through week 148.

The study, “Durable efficacy of dolutegravir (DTG) plus lamivudine (3TC) in antiretroviral treatment-naïve adults with HIV-1 infection - 96-week results from the GEMINI studies,” was presented on Wednesday, July 24, 2019, at IAS 2019 in Mexico City, Mexico.