The GEMINI-1&2 studies in treatment-naïve adults with screening HIV-1 RNA ≤500,000c/mL showed dolutegravir+lamivudine (DTG+3TC, 2DR) was non-inferior to dolutegravir+tenofovir disoproxil/emtricitabine (DTG+TDF/FTC, 3DR) at Week 48 by FDA snapshot algorithm; 91% (655/716) in the 2DR group versus 93% (669/717) in the 3DR group achieved HIV-1 RNA <50c/mL. Abbott RealTime HIV-1 assay used in the studies measures viral load (VL) from 40c/mL to 10,000,000c/mL, and provides qualitative target detected (TD) or target not detected (TND) for VL<40c/mL. Clinical and subject management implications of more stringent low level VL data needs clarification. We assessed the proportion of participants with TND over time and by baseline (BL) VL for 2DR versus 3DR.
Subjects were randomised 1:1 to treatment with 2DR or 3DR. The proportion of subjects with HIV-1 RNA <40 c/mL and TND status at Week 48 was analysed using a Cochran-Mantel-Haenszel test stratified by plasma HIV-1 RNA (≤100,000 vs >100,000 copies/mL) and CD4+ cell count (≤200 vs >200 cells/mm3) at BL. Proportion of subjects with TND Status were summarised by Visit and at Week 48 by BL HIV-1 RNA Subgroup. Time to Plasma HIV-1 RNA <40 c/mL and TND Status Overall and by BL HIV-1 RNA Subgroup were estimated using non-parametric Kaplan-Meier method.
At Week 48 similar proportion of subjects had snapshot TND in the 2DR and 3DR arms (77% [553/716] vs 73% [525/717], adjusted difference 3.8%, 95% CI -0.6%, 8.2%) and proportions were also similar at earlier visits: Weeks 4 (34% vs 32%), 8 (52% vs 49%), 12 (60% vs 57%), 16 (59% vs 56%), 24 (65% vs 63%), and 36 (65% vs 68%). While similar response rates were seen in subjects with BL VL ≤100,000c/mL, response rates were higher in 2DR vs 3DR subjects with BL VL >100,000 c/mL. (Table). Median time for 2DR vs 3DR to TND was 57 days for both overall, 57 days for both in ≤100,000c/mL at BL strata, and 113 days vs 169 days for BL >100,000c/mL subgroup.
DTG/3TC and DTG+TDF/FTC had similar proportions of TND by snapshot at all Weeks. Snapshot response rates based on TND status at Week 48 were similar between arms at ≤100,000c/mL BL subgroup and higher for DTG/3TC in >100,000c/mL BL category. Median time to TND was similar overall and in BL VL≤100,000c/mL subgroup, and less for DTG/3TC vs DTG+TDF/FTC if >100,000c/mL at BL. These data, utilizing a more stringent snapshot criteria, continue to demonstrate the effectiveness and potency of DTG+3TC in treatment-naïve subjects.