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ELSULFAVIRINE AS COMPARED TO EFAVIRENZ IN COMBINATION WITH TDF/FTC: 48-WEEK STUDY
Robert Murphy1, Alexey V. Kravchenko2, Elena Orlova-Morozova3, Firaya Nagimova4, Oleg Kozirev5, Tatyana Shimonava6, Marina Deulina2, Natalia Vostokova7, Olga Zozulya7, Vadim Bichko8
1Northwestern Univ, Chicago, IL, USA,2Russia AIDS Federal Cntr, Moscow, Russian Federation,3Moscow Region AIDS Cntr, Moscow, Russian Federation,4Republic Tartarstan AIDS Cntr, Kazan, Russian Federation,5Volgograd Region AIDS Cntr, Volgograd, Russian Federation,6Moscow City AIDS Cntr, Moscow, Russian Federation,7IPHARMA Moscow, Moscow, Russian Federation,8Viriom, Inc, San Diego, CA
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.
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.
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.
Elpida was significantly better tolerated than EFV-based therapy offering a safer alternative to EFV-based ART.