CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

452LB ELSULFAVIRINE AS COMPARED TO EFAVIRENZ IN COMBINATION WITH TDF/FTC: 48-WEEK STUDY Robert Murphy 1 , Alexey V. Kravchenko 2 , Elena Orlova-Morozova 3 , Firaya Nagimova 4 , Oleg Kozirev 5 , Tatyana Shimonava 6 , Marina Deulina 2 , Natalia Vostokova 7 , Olga Zozulya 7 , Vadim Bichko 8 1 Northwestern Univ, Chicago, IL, USA, 2 Russia AIDS Federal Cntr, Moscow, Russian Federation, 3 Moscow Region AIDS Cntr, Moscow, Russian Federation, 4 Republic Tartarstan AIDS Cntr, Kazan, Russian Federation, 5 Volgograd Region AIDS Cntr, Volgograd, Russian Federation, 6 Moscow City AIDS Cntr, Moscow, Russian Federation, 7 IPHARMA Moscow, Moscow, Russian Federation, 8 Viriom, Inc, San Diego, CA, USA Background: Elpida® (VM1500) is the prodrug of Elsulfavirine (VM1500A), a new potent non-nucleoside reverse transcriptase inhibitor with unique pharmacokinetic properties (T1/2 is ~8 days). A 20 mg once daily dosing was chosen for further study based on 12-week efficacy, pharmacology and safety data. Methods: Compare the efficacy and safety of an ART regimen including Elpida or Efavirenz (EFV) plus tenofovir/emtracitabine (TDF/FTC). Phase IIb randomized, placebo- controlled, double-blind, multicenter study in ART-naïve HIV-1-infected patients treated for 48 weeks. Patients were randomized 1:1 to receive; 1) Elpida 20 mg QD, or 2) EFV 600 mg QD. All patients were treated with TDF/FTC. Results: 120 patients enrolled, 60 Elpida/60 EFV. Baseline plasma HIV RNA median was 4.7-4.8 log10 copies/ml; median CD4+ T lymphocyte count was 349 and 379 cells/mm3 for Elpida and EFV respectively. A total of 55/60 (91.7%) Elpida and 47/60 (78.3%) EFV (p=0.041) completed treatment. At Week 48 of therapy 45/55 (81%) of Elpida and 35/47 (73.7%) of EFV patients had HIV-1 RNA values <50 copies/ml (MITTI-analysis) and all patients in both groups who completed treatment had HIV-1 RNA value < 400 copies/ml. Patients with baseline HIV-I RNA > 100 000 copies/ml, with HIV RNA <50 copies/mL at week 48 were 14/18 (77.7%) and N15/22 (68.2%) of patients respectively after 48 weeks of therapy. No patient demonstrated virologic failure defined as two consecutive HIV RNA plasma levels of >400copies/ml. CD4+ T lymphocyte counts increased at Week 48 by 179 and 182 cells/mm3 respectively. Median CD4/CD8 ratio increased in both groups from 0.41 to 0.78 and from 0.34 to 0.63 respectively. Study drug-associated adverse events were observed in N22/60 (36.7%) of Elpida patients and 45/58 (77.6%) of EFV patients (p <0.0001). AEs of special interest (CNS disorders, skin disorders) with a frequency > 5% occurred in 31.7% and 62.1% of patients respectively (p = 0.008). The most frequent were headache (15% and 24.1%), dizziness (6.7% and 27.6%), sleep disorders (5% and 20.7%). Only EFV patients had abnormal dreams (17.2%), skin rash (17.2%), and pruritus (5.2%). Only 5 patient discontinued Elpida (2 AE [1 pregnancy], 1 lack of compliance, 1 LTFU, 1 withdrew consent), and 13 patients discontinued EFV (7 AE, 5 LTFU, 1 withdrew consent) because of drug-related AEs. Conclusion: Elpida was significantly better tolerated than EFV-based therapy offering a safer alternative to EFV-based ART. 453 SIGNIFICANT EFFICACY & LONG-TERM SAFETY DIFFERENCE WITH TAF-BASED STR IN NAÏVE ADULTS Jose R. Arribas 1 , Melanie Thompson 2 , Paul E. Sax 3 , Bernhard Haas 4 , Cheryl McDonald 5 , David Wohl 6 , Edwin DeJesus 7 , Amanda Clarke 8 , Moupali Das 9 , Scott McCallister 9 1 Hosp Univ La Paz, Madrid, Spain, 2 AIDS Rsr Consortium of Atlanta, Atlanta, GA, USA, 3 Brigham and Women’s Hosp, Boston, MA, USA, 4 Hosp Graz West, Graz, Austria, 5 Tarrant County Infectious Disease Associates, Fort Worth, TX, USA, 6 Univ of North Carolina at Chapel Hill, Chapel Hill, NC, USA, 7 Orlando Immunol Cntr, Orlando, FL, USA, 8 Brighton & Sussex Univ Hosps NHS Trust, Brighton, UK, 9 Gilead Scis, Inc, Foster City, CA, USA Background: Two randomized, controlled, double-blinded multinational Phase 3 trials compared tenofovir alafenamide (TAF) vs tenofovir disoproxil fumarate (TDF), each in single-tablet regimens coformulated with elvitegravir/cobicistat/emtricitabine (E/C/F). At Week (W) 48, E/C/F/TAF was statistically noninferior to E/C/F/TDF for the proportion of subjects with HIV-1 RNA <50 copies(c)/mL and had significant improvements in renal and bone safety endpoints. We now describe follow up of blinded data through W144, including longer-term safety data and prespecified <20 c/mL secondary endpoint. Methods: ARV naïve participants randomized 1:1 to receive E/C/F/TAF (TAF) or E/C/F/TDF (TDF). W144 viral suppression (HIV-1 RNA <50 and <20 c/mL) by FDA snapshot analysis, predefined bone and renal safety, and tolerability endpoints are reported. Results: 1,733 HIV-infected adults were randomized and treated: 15%women, 43% non-white, 23% viral load >100,000 c/mL. Median baseline characteristics: age 34 yrs, CD4 count 405 cells/µL, and VL 4.58 log10 c/mL. At W144, TAF met prespecified criteria for both noninferiority and superiority to TDF by FDA snapshot algorithm (HIV-1 RNA <50 and <20 c/mL) (Table 1). Mean % decrease in BMD was significantly less in the TAF group for both lumbar spine and total hip (Table 1). As shown in Table 1, multiple measures of renal safety were significantly better for participants randomized to TAF. There were no cases of renal tubulopathy in the TAF arm vs 2 on TDF. No participants on TAF had renal-related discontinuations vs 12 on TDF (p<0.001). Participants on TAF had greater increases in TC, LDL, and HDL (Table 1), with no difference in the rate of initiation of lipid-modifying agents (TAF: 5.5% vs TDF: 5.8%). Conclusion: Through W144, participants on E/C/F/TAF had a significantly higher rate of virologic suppression (<50 c/mL) than those on E/C/F/TDF, driven by fewer participants on E/C/F/TAF with no W144 data. Participants on E/C/F/TAF also had a significantly higher rate of virologic suppression (<20 c/mL), driven by fewer participants on E/C/F/TAF with viral load ≥20 c/mL. E/C/F/TAF continued to have a statistically superior bone and renal safety profile compared to E/C/F/TDF, demonstrating significant safety advantages over E/C/F/TDF through 3 years of treatment. Individuals on TAF had greater plasma lipid changes, but proportions starting lipid-lowering therapy were comparable.

Poster and Themed Discussion Abstracts

CROI 2017 189