Phase III GEMINI 1 & 2 studies of a two-drug regimen of dolutegravir and lamivudine show non inferiority to three drug regimen in treatment-na�ve HIV-I patients- GSK.

ViiV Healthcare presented at the 22nd International AIDS conference in Amsterdam 48-week results from the phase III GEMINI 1 & GEMINI 2 studies, assessing the safety and efficacy of a two-drug regimen (2DR) of dolutegravir (DTG) and lamivudine (3TC) compared to a three-drug regimen of dolutegravir and two nucleoside reverse transcriptase inhibitors (NRTIs), tenofovir disoproxil fumarate/emtricitabine (TDF/FTC), in treatment-naïve, HIV-1 infected adults with baseline viral loads up to 500,000 copies per millilitre (c/mL).

The studies met their primary endpoint for non-inferiority based on plasma HIV-1 RNA <50c/mL, a standard measure of HIV control, at Week 48. In a pooled analysis, 91% (655/716) of patients taking DTG + 3TC had HIV-1 RNA<50 copies/mL compared with 93% (669/717) of patients taking DTG +TDF/FTC [adjusted difference -1.7% (95% CI: -4.4%, 1.1%)].

Pedro Cahn, principal investigator for the GEMINI study programme said: “For the last 15-20 years, the standard of care for HIV has revolved around three-drug regimens. Now that we have more potent drugs, the focus is shifting to tolerability and convenience. The GEMINI studies show that we can get the efficacy of three drugs in a two-drug regimen with the tolerability and drug interaction profile of DTG and 3TC. These are important findings for people living with HIV who will spend their lifetime taking drugs to suppress their virus. The studies have the potential to expand the treatment paradigm for first-line therapy of people living with HIV.”

Results show broadly consistent results for virus suppression across individuals with higher viral load (more than 100,000 copies of viral RNA per millilitre of blood plasma [>100,000 c/mL]) and lower viral load (<=100,000 c/mL) HIV-1 plasma RNA. Rates of virologic failure were less than 1% across all arms of the study. No patient who experienced virologic failure in either treatment arm developed treatment-emergent resistance. The percentage of patients that withdrew due to adverse events was 2% in each study arm (GEMINI 1 DTG + 3TC arm: n=7, GEMINI 1 DTG + TDF/FTC arm n=8, GEMINI 2 DTG + 3TC arm n= 8, GEMINI 2 DTG + TDF/FTC arm n = 8). Pooled results show that the most common ( greater than 5%) adverse events across the studies were headache, diarrhoea and nasopharyngitis in both arms (DTG + 3TC arm: 10%, 9%, and 8%, respectively, DTG + TDF/FTC: 10%, 11%, and 11%, respectively).Drug-related adverse events were less frequent in patients on the DTG/3TC regimen (126/716, 18%), compared with those on the DTG + TDF/FTC regimen (169/717, 24%).

ViiV Healthcare intends to seek regulatory approval for a fixed-dose combination of DTG and 3TC later this year. DTG and 3TC, as a 2DR, is not yet approved for use by the FDA.

Comment: Results from the studies, called GEMINI 1 and 2, showed GSK's combination to be as effective in controlling levels of the HIV virus as the three-drug regimen containing Gilead Sciences' competing therapy Truvada — data that GSK hopes will convince physicians to more widely consider two-drug combinations.