CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

genotype showed major RT/PR resistance mutations. CVWwas 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. Results: 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/mm 3 ; 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. Conclusion: 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. 484 HIV-1 REPLICATION AT <50 C/ML TO 148 WEEKS FOR SWORD-1/SWORD-2 STUDIES WITH DTG+RPV Mark Underwood 1 , Kostas Angelis 2 , Ruolan Wang 1 , Joe Horton 3 , Veerle Van Eygen 4 , Jessica Matthews 1 , Lesley Kahl 5 , Jean van Wyk 5 , Brian Wynne 1 1 ViiV Healthcare, Research Triangle Park, NC, USA, 2 GlaxoSmithKline, Uxbridge, UK, 3 PAREXEL International, Durham, NC, USA, 4 Janssen, Beerse, Belgium, ViiV Healthcare, Brentford, UK Background: The SWORD studies demonstrated non-inferiority on switch to dolutegravir (DTG) + rilpivirine (RPV) vs continuing a 3- to 4-drug Current Antiretroviral Regimen (CAR) for 48 weeks, and also showed long term suppression to HIV-1 RNA <50 c/mL. The clinical significance of low-level viral load (VL) <50c/mL remains unclear. We present here low level qualitative VL data from the Phase 3 SWORD studies up to Week 148. Methods: Adults with VL<50 c/mL for ≥6 months were randomized to switch to DTG+RPV (Early Switch (ES) group) for 148 weeks or continue CAR. CAR participants <50c/mL at Week 48 switched at Week 52 (Late Switch (LS) group) to receive DTG+RPV for 96 weeks. The Abbott Realtime assay measures VL quantitatively from 40c/mL to 10,000,000c/mL; when VL<40c/mL it returns qualitative Target Detected (TD) or Target Not Detected (TND) results. We explored participants’ TND and TD status over time, overall and by Baseline TD or TND status. Results: 1024 participants were randomized and exposed (ES DTG+RPV 513; CAR 511) across both studies; 477 CAR participants switched to DTG+RPV at Week 52. The proportions of participants with TND at all visit weeks were similar and did not decline over time (Figure); TND ranges across visits were 75%-88% in the ES group, 79%-90% in the LS group and 79%-88% in the CAR group. Participant proportions with BL TND and TND at all visits through 48 Weeks exposure in comparator ES DTG+RPV, LS DTG+RPV, and CAR groups were respectively 47% (180/383), 52% (189/367), and 53% (215/408), and for

participants with BL TD the proportions with TND at all visits were respectively 19% (18/94), 33% (25/76), and 19% (13/70). Among participants in the ES DTG+RPV group with pre-switch TND vs TD, the proportions with TND at all visits through Week 148 were respectively 23% (79/341) vs 10% (8/84), and among LS DTG+RPV group the proportions with TND through Week 148 (96 weeks of DTG+RPV) were 40% (142/352) vs 20% (15/76). In the ES DTG+RPV group, 20% of the 433 participants who reached Week 148 had TND at all visits, and in the LS DTG+RPV group, 36% of the 434 participants who reached Week 148 (with 96 weeks of DTG+RPV exposure) had TND at all visits. Conclusion: The frequency of participants with TND status under DTG+RPV remained high across all visits with no decline observed through 148 weeks. This is supportive evidence that long term treatment with DTG+RPV is efficacious in virologic suppression to <50c/mL.

Poster Abstracts

485 LONG-TERM DTG-3TC SWITCH EFFICACY IN PATIENTS WITH ARCHIVED 3TC RESISTANCE Rosa de Miguel 1 , David Rial 2 , Lourdes Domínguez-Domínguez 2 , Rocio Montejano 1 , Andrés Esteban-Cantos 1 , Otilia Bisbal 2 , Natalia Stella-Ascariz 1 , Paula Aranguren 2 , Mónica García-Álvarez 2 , Belen Alejos 3 , Maria Lagarde 2 , Jose I. Bernardino 1 , Federico Pulido 2 , Jose R. Arribas 1 , for the ART-PRO, PI16/00837- PI16/00678 Study Group 1 Hospital La Paz Institute for Health Research, Madrid, Spain, 2 Hospital Universitario 12 de Octubre, Madrid, Spain, 3 Institute of Health Carlos III, Madrid, Spain Background: ART-PRO pilot trial showed that at 48 weeks DTG+3TC was effective in maintaining virologic control despite history of lamivudine resistance and persistence of archived 3TC mutations detected by NGS. Here we present resistance analysis and virologic outcomes after 80 weeks of DTG+3TC treatment. Methods: Open, single-arm, pilot trial including HIV-1 infected adults, INSTI-naïve, CD4 count >350 cell/μL, VL< 50 copies/mL for 1 year prior to study entry. Participants were excluded if baseline proviral DNA population genotyping detected M184V/I or K65R/E/N. Baseline proviral DNA NGS genotype was retrospectively performed to detect resistance minority variants. All participants were switched to DTG+3TC. Results: 41 participants (78%male) switched to DTG+3TC: 21 participants had M184V/I or K65R/E/N in historical plasma genotyping and 20 had not. At baseline: median CD4 661, ART duration 18 years, duration of suppressed plasma HIV RNA 7.7 years, number of prior ART regimens 6. Participants with historical 3TC resistance were significantly less likely to receive a regimen including 3TC before the switch (p<0.001). NGS of baseline proviral DNA detected M184V/I at >5%/>20% thresholds in 67%/29% of participants with and 15%/5% of participants without history of 3TC resistance. K65R was detected in proviral DNA by NGS only in participants with historical resistance to 3TC (9.5%/5% at the >5%/>20% cut-off respectively). At week 80, 87.8% of participants (37/41) remained with VL< 50 copies/mL (Table 1). There were no virologic failures through week 80. Of the 21 participants with historical 3TC resistance, 3 prematurely discontinued with suppressed viremia (2 protocol violations, one AE [insomnia, W8]). One participant without historical 3TC resistance declined to participate in the 144w study extension. There were 12 blips, 6 in the group with historical resistance. There were 30 related AE, 4/30 were severe and only 1 led to discontinuation. Conclusion: In this pilot trial, DTG+3TC was effective maintaining long-term virologic control after 80 weeks of follow up despite history of 3TC resistance

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