CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

Poster and Themed Discussion Abstracts

448 RALTEGRAVIR/EMTRICITABINE/TENOFOVIR IN HIV-2 INFECTION (ANRS 159 VIH-2 PILOT TRIAL) Sophie Matheron 1 , Diane Descamps 1 , Sébastien Gallien 2 , Amel Besseghir 3 , Roland Tubiana 4 , Florence Damond 1 , Fideline Collin 3 , Francoise Brun-Vezinet 1 , Genevieve Chene 3 , for the ANRS 159VIH2 trial Study Group 1 Hopital Bichat-Claude Bernard, AP-HP, Paris, France, 2 Hopital Saint Louis, AP-HP, Paris, France, 3 INSERM, Bordeaux, France, 4 Hopital Pitié-Salpétrière, AP-HP, Paris, France Background: We hypothesized that cART involving an integrase inhibitor (raltegravir) and 2 NRTIs (emtricitabine, tenofovir) could improve the gain in CD4 lymphocytes count (CD4) in HIV-2. Methods: This multicenter non-comparative trial included ARV-naïve adults infected with HIV-2 only, with either previous CDC group B or C defining event, or a CD4 count <500/ μL or CD4 decrease >50 cells/μL/year over the last 3 years or confirmed plasma HIV-2 RNA (pVL) ≥100 copies/mL. The primary endpoint was a composite criterion: proportion of participants surviving at 48 weeks (W48) without any of the following events: CD4 gain <100/μL at W48 compared to baseline (W0) CD4 count, pVL ≥40 cp/mL fromW24 confirmed within the next 4 weeks, raltegravir permanent discontinuation, new B or C event. Missing data were considered as failure. Ultrasensible pVL (uspVL) and total DNA were determined using “in-house” PCR assays Results: From August 2012 to February 2015, 30 patients (67%women) were included. At baseline, they were aged 49 years, had HIV-2 infection diagnosed for 11 years (InterQuartile Range [IQR]=8 to 14) and median CD4 nadir of 351/µL; median CD4 count was 436/µL (IQR=314 to 507); pVL was ≥40 copies/mL in 20/30 (67%) participants (median=2.5 log10 copies/mL); uspVL was ≥5 copies/mL in 23/25 participants (92%); total DNA was >6 copies/PCR in 8/25 participants (32%) (median=225.5 copies/106 PBMC). At W48, the composite endpoint of success was reached in 12/30 patients (40%; 95% Confidence Interval 22.7 to 59.4). Eighteen patients failed due to CD4 gain <100/µL (n=15), pVL ≥40 copies/mL (n=1) or withdrawal before W48 (n=2). pVL was ≥5 copies/mL in 2/15 patients (13%). Total DNA was >6 copies/PCR in 3/26 (11.5%). Among the 22 patients with baseline CD4 <500/µL and the 8 with CD4 ≥500/µL, 36% and 50% experienced treatment success, respectively. Median CD4 change was +87/µL (IQR +38 to +213) in the 28 patients with complete follow-up; +115/µL and +70/µL in those with baseline pVL ≥40 and <40 copies/mL, respectively. No serious adverse reaction was reported. Conclusion: Overall, first line raltegravir-containing cART was well tolerated and yielded therapeutic success in 40% of HIV-2 patients at one year, comparable to that reported with a PI containing-regimen. Failure was mainly explained by a lower CD4 gain than expected. At W48, uspVL and total DNA were undetectable in about 90% of participants with available measurement. 449LB LONG-ACTING IBALIZUMAB IN PATIENTS WITH MULTI-DRUG RESISTANT HIV-1: A 24-WEEK STUDY Stanley Lewis 1 , Jeffry Fessel 2 , Brinda Emu 3 , Shannon Schrader 4 , Princy Kumar 5 , Gary J. Richmond 6 , Steven Weinheimer 1 , Christian Marsolais 7 1 TaiMed Biologics USA, Irvine, CA, USA, 2 Kaiser Permanent Med Cntr, San Fransisco, CA, USA, 3 Yale Univ, New Haven, CT, USA, 4 Schrader Clinic, Houston, TX, USA, 5 Georgetown Univ, Washington, DC, 6 Gary J Richmond MD PA, Ft Lauderdale, FL, USA, 7 Theratechnologies, Inc, Montreal, Canada Background: Multi-drug resistant (MDR) HIV-1 has been associated with a higher risk of disease progression and death. Antiretroviral agents (ARVs) with newmechanisms of action are necessary for patients with MDR HIV-1. The humanized monoclonal antibody, ibalizumab (IBA), is a long-acting ARV with a unique binding specificity allowing it to block viral entry into host cells. In the registrational Phase 3 study in MDR HIV-1 patients, TMB-301, IBA previously showed significant viral load (VL) reductions 7 days after initial dosing when added to a failing ARV regimen. Here, we describe the sustained efficacy, safety and tolerability of IBA through Week (wk) 24 of treatment. Methods: TMB-301 is an open-label study investigating the antiviral activity and safety of IBA plus an optimized background regimen (OBR) in treatment-experienced patients with MDR HIV-1. Following a 7-day monitoring period of patients on a failing ARV regimen, an intravenous (IV) loading dose of 2000 mg IBA was administered (functional monotherapy). On Day 14, an OBR was added with at least one additional sensitive agent and patients continued on an IV maintenance dose of 800 mg IBA every two wks for 24 wks. Efficacy and safety endpoints were evaluated. Results: Enrolled patients (n=40) had a median Baseline (BL) VL of 4.6 log10 (18% BL VL ≥100,000 copies/mL) and a median BL CD4+ T cell count of 73 cells/µL. Resistance testing at BL showed 53% and 35% of patients had exhausted ≥3 and 4 ARV classes, respectively, and 16% of patients had HIV-1 resistant to all approved ARVs. 43% of patients required an investigational agent in OBR. At Wk 24, using the ITT – Missing Equals Failure (ITT-MEF) analysis, the mean change from BL VL was -1.6 log10 with 55% and 48% of patients having a ≥1 log10 and ≥2 log10 reduction, respectively. Viral load <50 and <200 HIV RNA copies/mL was reached in 43% and 50% of patients, respectively. Other efficacy outcomes are presented on Table 1. Most treatment-emergent adverse events reported were mild to moderate in intensity. Nine patients had a serious adverse event, of which one (immune reconstitution inflammatory syndrome) was considered drug-related. Nine patients discontinued the study prior to completion. Conclusion: Bi-weekly IBA plus OBR maintained virologic efficacy and was well tolerated through Wk 24 in patients with very limited treatment options due to resistance to approved ARV agents.

CROI 2017 187