New studies of a two-drug, integrase inhibitor–based regimen, presented at the International AIDS Society Conference on HIV Science, provide additional data to challenge the three-drug HIV treatment paradigm.
In the results of one study, known as TANGO (NCT03446573), switching to the fixed-dose combination of dolutegravir (DTG) plus lamivudine (3TC) from a tenofovir alafenamide (TAF)–based three- or four-drug regimen maintained virologic suppression at 48 weeks in HIV-1 infected adults, an investigator said, and was noninferior to continuing TAF-based therapy.
In another presentation, updating results of the GEMINI-1 (NCT02831673) and GEMINI-2 studies (NCT02831764), a researcher said the DTG+3TC combination remained noninferior to DTG plus tenofovir/emtricitabine (TDF/FTC) at week 96 in antiretroviral (ART) treatment-naive adults with HIV-1 infection, with no treatment-emergent resistance and no increase in risk of virologic failure.
,” according to IAS Past President Pedro Cahn, MD, PhD, of Fundación Huésped, Buenos Aires, who presented the updated GEMINI study results.
“We don’t mean to say now everything should be dual therapy, and we are going to wipe out all other options, but I think we have another strong option for initiating therapy, and probably also for switch therapy,” Dr. Cahn said in a press conference.
Dr. Cahn presented an updated analysis of GEMINI-1 and GEMINI-2, two identically designed phase 3 randomized clinical trials including a total of 1,400 patients.
The 48-week results from those trials, presented in 2018, showed for the first time that a dual-therapy combination of an integrase inhibitor with 3TC was noninferior to the triple-drug regimen of DTG+TDF/FTC, Dr. Cahn said.
In the updated analysis, including 96 weeks of data, the two-drug regimen remained noninferior to the three-drug regimen, according to the investigator.
A total of 11 patients on DTG+3TC and 7 on DTG+TDF/FTC met virologic withdrawal criteria through week 96, with no treatment-emergent resistance mutations seen in either arm, according to results reported in the study abstract.
The proportion of subjects with plasma HIV-1 RNA below 50 c/mL at week 96 was 86% for the two-drug regimen and 90% for the three-drug regimen (adjusted difference, –3.4; 95% confidence interval, –6.7 to 0.0), the reported data showed.
Drug-related adverse events were numerically more common in the three-drug arm, though rates of adverse event–related withdrawal were low in both arms, according to investigators.
The strategy of switching to DTG+3TC was evaluated in the randomized, phase 3 TANGO trial, which included 741 subjects who were already virally suppressed on a TAF-based three- or four-drug regimen. After 48 weeks of therapy, the two-drug regimen was noninferior to remaining on TAF-based therapy in terms of achieving and maintaining viral suppression, according to investigator Jean van Wyk, MB, ChB, Global Medical Lead for dolutegravir at ViiV Healthcare.
Safety outcomes were similar between the arms, though the absolute number of treatment-related adverse events was higher in the DTG+3TC arm “as expected in a switch study,” Dr. van Wyk said.