CROI 2019 Abstract eBook

Abstract eBook

Poster Abstracts

resistance to at least 1 NRTI and 26 (9%) had minor resistance to at least one PI. 44% of participants achieved VL suppression at week 48. In both unadjusted and adjusted analysis (table), older age, lower baseline HIV-1 RNA, higher CD4 count, and lack of resistance to any NRTI (multivariable only) were significantly associated with higher virologic suppression rate at week 48. Associations with sex and with CPI+SOC were not statistically significant. 145 (51%) experienced confirmed virologic failure ≥ 1000 c/mL and 141 had GT available at failure; 48 (34%) had development of new resistance mutations, predominantly NRTI- related. Conclusion: In this 3rd-line ART trial in RLS, fewer than 50% of participants with no lopinavir resistance at entry who continued their 2nd-line ART had VL suppression at 48 weeks. Participants with more advanced disease or any resistance mutations had worse rates of suppression. This group likely represents individuals with continued poor ARV adheren

wk 96. Grade 3-4 and serious AEs were similar across subgroups, with a low percentage of AEs leading to D/C (Table). eGFR improved or was stable in the D/C/F/TAF arms across subgroups (Table). Wk 96 results for the late switch arm were consistent with wk 48 results for D/C/F/TAF (data not shown). Conclusion: Through 96 wks, D/C/F/TAF had a high genetic barrier to resistance and maintained high response rates, with few discontinuations due to AEs and favorable renal outcomes across patient subgroups in ART-naïve and experienced virologically suppressed adults.

Poster Abstracts

501 INTEGRATED EFFICACY ANALYSIS OF DORAVIRINE IN HIV-1-INFECTED TREATMENT-NAIVE ADULTS Chloe Orkin 1 , Jean-Michel Molina 2 , Johan Lombaard 3 , Wing-Wai Wong 4 , Edwin DeJesus 5 , Anthony Rodgers 6 , Xia Xu 6 , Sushma Kumar 6 , Elizabeth Martin 6 , George G. Hanna 6 , Carey Hwang 6 1 Queen Mary University of London, London, UK, 2 Hôpital Saint-Louis, Paris, France, 3 Josha Research, Bloemfontein, South Africa, 4 Taipei Veterans General Hospital, Taipei, Taiwan, 5 Orlando Immunology Center, Orlando, FL, USA, 6 Merck & Co, Inc, Kenilworth, NJ, USA Background: DOR is a non-nucleoside reverse transcriptase inhibitor (NNRTI) with once-daily dosing and potent in vitro activity against wild-type virus and the most common NNRTI-resistant variants (K103N, Y181C, G190A). DOR has demonstrated non-inferior efficacy to darunavir plus ritonavir (DRV+r) and efavirenz (EFV) in two ongoing, double-blinded, phase 3 trials: DRIVE-FORWARD (NCT02275780) and DRIVE-AHEAD (NCT02403674). Methods: This prespecified analysis pooled Week 48 data from DRIVE- FORWARD and DRIVE-AHEAD. Data from the DOR groups were pooled, in which 747 participants received DOR/3TC/TDF or DOR (100 mg QD) with FTC/TDF or ABC/3TC. The control groups were analyzed separately, in which 383 received DRV+r (800/100 mg QD) with FTC/TDF or ABC/3TC, and 364 received EFV/FTC/ TDF (600/200/300 mg QD). Efficacy was assessed by proportion of participants with HIV-1 RNA <50 copies/mL (primary) and change in CD4+ T-cells (secondary) after 48 weeks of treatment. Results: At Week 48, HIV-1 RNA <50 copies/mL was achieved by 84.1% of DOR- treated participants versus 79.9% of the DRV+r, and 80.8% of the EFV/FTC/TDF groups (Table). No clinically meaningful differences in proportions of patients with HIV-1 RNA <50 copies/mL was seen across demographic/prognostic subpopulations, including baseline plasma HIV-1 RNA (≤ vs >100,000 copies/ mL), gender (male/female), race (white vs black/African American), ethnicity (yes vs no Hispanic/Latino), and subtype (B vs non-B). Mean increases from baseline in CD4+ T-cell count at week 48 were 195.5 cells/mm 3 for DOR, 185.6 cells/mm 3 for DRV+r, and 188.4 cells/mm 3 for EFV/FTC/TDF. Conclusion: DOR, as a single entity (administered in combination therapy with other antiretroviral agents) and as a fixed-dose combination consisting of DOR/3TC/TDF, was efficacious compared with DRV+r and EFV as assessed by the proportion of HIV-1-infected, treatment-naïve adults with HIV-1 RNA <50 copies/mL. Consistent efficacy was seen regardless of demographic/prognostic baseline characteristics.

500 WEEK 96 SUBGROUP ANALYSES OF D/C/F/TAF IN HIV-1 TREATMENT- NAIVE & SUPPRESSED ADULTS Gregory D. Huhn 1 , Edwin DeJesus 2 , Pierre-Marie Girard 3 , Cheryl McDonald 4 , Cristina Mussini 5 , Christoph D. Spinner 6 , John Jezorwski 7 , Romana Petrovic 8 , Erika Van Landuyt 8 , Erkki Lathouwers 8 , Kimberley Brown 8 , Bryan Baugh 7 , for the AMBER/EMERALD Study Groups 1 Cook County Health & Hospitals System, Chicago, IL, USA, 2 Orlando Immunology Center, Orlando, FL, USA, 3 Pierre and Marie Curie University, Paris, France, 4 Tarrant County Infectious Disease Associates, Fort Worth, TX, USA, 5 University of Modena and Reggio Emilia, Modena, Italy, 6 Technical University of Munich, Munich, Germany, 7 Janssen Research & Development, Pennington, NJ, USA, 8 Janssen, Beerse, Belgium Background: Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10mg, currently approved in the EU, US and other countries, is being investigated in two Phase 3 randomized non-inferiority trials, EMERALD (virologically suppressed adults; NCT02269917) and AMBER (ART- naïve adults; NCT02431247). We present a wk 96 preplanned subgroup analysis of the D/C/F/TAF arms by baseline viral load (VL) and CD4+ count (screening stratification factors), WHO clinical stage in AMBER, and prior virologic failure (VF), ART experience, screening bPI (stratification factor) and boosting agent in EMERALD. Methods: Patients in the D/C/F/TAF and control arms of both trials (study designs described previously) continued on or switched to D/C/F/TAF in a single-arm, open-label extension phase until wk 96 provided they consented and continued to derive benefit. Wk 96 efficacy endpoints were % patients with cumulative confirmed VL≥50c/mL (virologic rebound) (EMERALD) and VL<50 c/mL (virologic response) and VL≥50c/mL (VF) (FDA snapshot) (both trials). No wk 96 comparisons were made between arms during the open-label phase. This analysis focuses on long-term efficacy and safety of D/C/F/TAF over 96 wks in the D/C/F/TAF arms. Results: In AMBER, high response and low VF rates were seen at wk 96 across the baseline VL, CD4+ count and WHO clinical stage subgroups (Table). In EMERALD, 58% had received ≥5 ARVs (including screening ARVs and boosters) and 15% had prior non-DRV VF. High response rates, low VF and low virologic rebound rates were maintained through wk 96 across ART experience and prior VF, and screening bPI and boosting agent subgroups (Table). In both trials, low denominators in some subgroups resulted in wider 95% CIs and data should be interpreted with caution. No DRV, primary PI or TFV RAMs were seen through

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