LAUSR

We address a data gap identified by Adams et al. [1], of virological efficacy outcomes and emergent drug resistance in HIV-1-infected, antiretroviral treatment (ART)naive participants with baseline (BL) viral loads (VL) >1,000,000 copies/ml. Initial ART regimens including an integrase strand transfer inhibitor (INSTI) cause a rapid decline in VL. In two cases described [1], the VL response on the single tablet regimen (STR) of co-formulated elvitegravir, cobicistat, emtricitabine and tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF) was <2 log10 copies/ml and associated with emergent drug resistance [1]. Double-blind, Phase III studies of EVG/COBI/FTC/TDF (Studies 102/103 and 128), and co-formulated elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide (EVG/COBI/FTC/TAF; Studies 104/111), have investigated the efficacy and safety of both EVG-containing STRs in ART-naive participants [2–10]. We present a post hoc analysis of efficacy of these STRs in participants with VL ≥1,000,000 copies/ml. Participants (n=64) analysed with VL ≥1,000,000 copies/ml were treated with either EVG/COBI/FTC/ TDF (n=32), EVG/COBI/FTC/TAF (n=9) or other ART regimens (efavirenz/emtricitabine/ tenofovir disoproxil fumarate [EFV/FTC/TDF, n=6], or atazanavir + ritonavir + fixed dosed TDF/FTC [ATV+RTV+FTC/TDF, n=17]). Virological success (VS) was achievement of HIV-1 RNA <50 copies/ml (Snapshot). Genotypic sensitivity to FTC and TDF was required, and to EFV or ATV (Studies 102, or 103 and 128, respectively). Integrase genotyping was performed at screening in Studies 104/111 [11]. Post-BL resistance testing was performed when VL [3] 400 copies/ml was confirmed at virological failure (VF). Adherence was monitored by pill count. BL VLs in the subgroup ranged from 1,030,000– 11,000,000 copies/ml, and 72% of participants had BL CD4+ T-cell count <200 cells/mm3 (Table 1). VL curves of participants through week (W) 48 are shown (Figure 1). By W4, participants randomized to either EVG-containing STR had median changes in VL from BL >-3.0 log10 copies/ml in all studies versus <-3.0 log10 copies/ml for participants on the other ART regimens (Table 1). In participants on either EVG-containing STR, the first achievement of HIV-1 RNA <50 copies/ml had occurred in 33% by W12, 67% by W24 and 97% by W48 (range W4–W60). Overall, 35/41 (85%) on EVG-containing STRs had HIV-1 RNA <50 copies/ml at W48. 38 of 41 (93%) participants on EVG-containing STRs achieved HIV-1 RNA <50 copies/ml by last available time point, although 2 participants discontinued the study (Table 1). Sixteen participants (39%) never had any subsequent blips in VL ≥50 copies/ml, 20 (49%) had at least one transient VL ≥50 to <400 copies/ ml and re-suppressed, and 2 (5%) had VL >400 copies/ ml and re-suppressed. 3 of 41 (7%) participants on the EVG-containing STRs (EVG/COBI/FTC/TDF [2] and EVG/COBI/FTC/TAF [1]) had VF, and met resistance Letter