Dolutegravir-lamivudine shows durable efficacy for HIV across patient subgroups

Treatment-naïve individuals with HIV continued to benefit from the dolutegravir-lamivudine regimen for nearly 3 years regardless of baseline disease characteristics and demographics, as shown by its noninferiority to dolutegravir plus tenofovir and emtricitabine observed in the subgroup analyses of the GEMINI trials presented at CROI 2021.

“The subgroup efficacy results at week 144 were generally consistent with the overall study results,” said the researchers. “[Our current findings] further demonstrate that dolutegravir-lamivudine is an effective initial treatment for HIV-infected patients across a spectrum of disease characteristics and patient populations.”

GEMINI-1 and -2 are identical phase III studies evaluating individuals (n=714 and 719, respectively) with screening HIV-1 RNA ≤500,000 c/mL, and without major viral resistance mutations to nucleoside reverse transcriptase inhibitors (NRTIs), non-NRTIs or protease inhibitors. Participants were randomized 1:1 to receive QD dolutegravir 50 mg, in combination with either lamivudine 300 mg, or tenofovir 300 mg/emtricitabine 200 mg. Participants were stratified by plasma HIV-1 RNA and CD4+ cell count. [CROI 2021, abstract 414]

A pooled analysis of GEMINI-1 and -2 demonstrate the noninferiority of dolutegravir-lamivudine to dolutegravir-tenofovir/emtricitabine, as reflected by the similar fractions of participants achieving plasma HIV-1 RNA <50 c/mL at week 144 (82 percent vs 84 percent; adjusted difference, –1.8, 95 percent confidence interval, –5.8 to 2.1).

Response rates were also similar in both the dolutegravir-lamivudine and the dolutegravir-tenofovir/emtricitabine arms regardless of baseline HIV-1 RNA levels (81 percent vs 84 percent [≤100,000 c/mL] and 82 percent vs 84 percent [>100,000 c/mL]).

The noninferiority of dolutegravir-lamivudine to dolutegravir-tenofovir/emtricitabine was consistent regardless of age (80 percent vs 83 percent [<35 years], 84 percent for both [35 to <50 years], and 83 percent for both [≥50 years]), gender (83 percent vs 84 percent [male] and 74 percent vs 84 percent [female]), or race (85 percent vs 86 percent [Whites], 67 percent vs 73 percent [African heritage], and 79 percent vs 82 percent [Asians]).

More participants on dolutegravir-lamivudine achieved confirmed virologic withdrawal* criteria through week 144 compared with those on dolutegravir-tenofovir/emtricitabine (n=12 vs 9).

However, response rates were lower among dolutegravir-lamivudine vs dolutegravir-tenofovir/emtricitabine recipients with CD4+ ≤200 cells/mm³ (67 percent vs 76 percent). “[Nonetheless, this] difference was smaller than [those observed] at weeks 48 and 96,” noted the researchers. “[M]ost reasons for nonresponse were unrelated to virologic efficacy or treatment regimen.”

These findings reinforce the previous GEMINI-1 and -2 results observed at weeks 48 and 96. The consistent noninferiority of dolutegravir-lamivudine to dolutegravir-tenofovir/emtricitabine for HIV patients across 3 years support the durable efficacy of dolutegravir-lamivudine in this patient setting.