In GEMINI-1&2, the dolutegravir (DTG) + lamivudine (3TC) 2-drug regimen (2DR) is non-inferior to the DTG + tenofovir/emtricitabine (TDF/FTC) 3-drug regimen (3DR) in HIV-1 ART-naïve participants at Weeks 48/96. Eleven participants on 2DR and seven on 3DR met protocol-defined Confirmed Virologic Withdrawal (CVW) criteria through Week 96. We present a detailed description of these CVWs.
Patients were stratified by viral load (VL) ≤/>100,000c/mL and CD4+ ≤/>200cells/mm3. Patients were not eligible if screening HIV-1 genotype showed major RT/PR resistance mutations. CVW was defined as two consecutive VLs meeting virologic non-response (VL ≥200c/mL after Week 24 or <1.0 log decline in VL by Week 12 unless HIV-1 RNA is <200c/mL) or virologic rebound criteria (≥200c/mL after prior suppression to <200c/mL). Monogram Bioscience performed integrase and RT/PR genotypic and phenotypic resistance testing on Day 1 and Virologic Withdrawal timepoint samples. We evaluated CVW patient baseline (BL) VL and CD4 characteristics, adherence, study drug interruption, resistance, and VL progression through the study course.
In GEMINI-1&2, 3 participants screen failed due to M184I/V resistance. Overall, 11 participants on DTG+3TC and 7 on DTG+TDF/FTC met CVW criteria through Week 96. Of these, 5 vs 2 CVWs occurred after Week 48. All CVWs experienced virologic rebound; none had VL blips (VLs between 50-<200c/mL with adjacent values <50c/mL) that preceded CVW. One DTG+3TC participant never suppressed to <50c/ml. Table 1 summarizes key information for CVWs in the DTG+3TC arm. Among the 11 and 7 participants on DTG+3TC vs DTG+TDF/FTC respectively: 9 vs 7 were infected with HIV-1 subtype B; 3 vs 2 had Baseline CD4 <200cells/mm3; 5 vs 3 had Baseline HIV-1 VLs >100,000c/mL; and HIV-1 VL decreased from CVW time point to the withdrawal (WD) visit ≥2 fold for 7 of 9 vs 4 of 5 cases with WD visit VLs. Resistance data were available for all samples except 2 cases on DTG+TDF/FTC where testing failed with HIV-1 VL below the assay cut-off; no treatment-emergent genotypic or phenotypic resistance in IN or RT was observed in any CVWs.
In GEMINI1&2, there were low and comparable numbers of participants meeting CVW through 96 weeks in the DTG+3TC and DTG+TDF/FTC arms without apparent predisposition by BL VL or CD4; no emergent genotypic/phenotypic resistance to INSTI/NRTIs was observed. These data further support the potency and durability of DTG+3TC.