Dolutegravir and lamivudine combination regimen met primary endpoint in 2 phase 3 studies of treatment-naïve patients with HIV.
Updated: October 19, 2018, at 10:35 AM
New results from 2 phase 3 studies evaluating the safety and efficacy of the 2-drug regimen of dolutegravir (DTG) and lamivudine (3TC) for treatment-naïve patients infected with HIV-1 with baseline viral loads up to 500,000 c/mL reveal that the 2-drug regimen is noninferior to a 3-drug regimen of DTG and 2 nucleoside reverse transcriptase inhibitors (NRTIs), tenofovir disoproxil fumarate/emtricitabine (TDF/FTC). The data were presented at the 22nd International AIDS Conference (AIDS 2018) in Amsterdam, the Netherlands.
The GEMINI 1 & 2 studies met their primary endpoints for noninferiority based on plasma HIV-1 RNA <50 c/mL. According to the researchers, rates of virologic failure were <1% and patients who experienced virologic failure did not develop treatment-emergent resistance.
“The GEMINI studies show that we can get the efficacy of 3 drugs in a 2-drug regimen with the tolerability and drug interaction profile of DTG and 3TC,” said Pedro Cahn, MD, PhD, principal investigator of the GEMINI studies said in a statement, “These are important findings for people living with HIV who will spend their lifetime taking drugs to suppress their virus. These studies have the potential to expand the treatment paradigm for first-line therapy of people living with HIV.”
The results are consistent for the suppression of HIV across individuals with higher viral loads (>100,000 c/mL) and lower viral loads (<=100,000 c/mL). In a pooled analysis, 81% of patients taking DTG +3TC had HIV RNA<50 c/mL compared with 93% of patients taking DTG+TDF/FTC.
Two-percent of patients in each study arm withdrew because of adverse events, the most common of which being headache, diarrhea, and nasopharyngitis (DTG + 3TC arm: 10%, 9%, and 8%, respectively. DTG + TDF/FTC: 10%, 11%, and 11%, respectively). Adverse events were less frequent in patients on the DTG/3TC regimen (18%) compared with those on DTG + TDF/FTC regimen (24%).
None of the patients who experienced virologic failure in either treatment arm developed treatment-emergent resistance, according to the statement.
“These data we have presented at AIDS 2018 provide further evidence that we should be rethinking the traditional approach to HIV treatment of using three or more drugs,” said John C. Pottage, Jr, MD, chief scientific and medical officer of ViiV Healthcare in the statement.
On October 17, 2018, ViiV announced that the company had submitted a New Drug Application (NDA) and priority review voucher to the US Food and Drug Administration (FDA) for a single-tablet, 2-drug regimen of DTG/3TC. The anticipated Prescription Drug User Fee Act (PDUFA) action date is in April of 2019.
Additionally, a marketing authorization application was submitted in September to the European Medicines Agency and other regulatory submissions are anticipated in the coming months.