CROI 2016 Abstract eBook

Abstract Listing

Oral Abstracts

154LB Ledipasvir/Sofosbuvir for 6Weeks in HIV-Infected Patients With Acute HCV Infection Jürgen K. Rockstroh 1 ; Sanjay Bhagani 2 ; Robert H. Hyland 3 ; ChoheeYun 3 ;Wei Zhang 3 ; Diana M. Brainard 3 ; John G. McHutchison 3 ; Patrick Ingiliz 4 ;Thomas Lutz 5 ; Mark Nelson 6 1 Medizinische Univsklinik, Bonn, Germany; 2 Royal Free Hosp, London, UK; 3 Gilead Scis, Inc, Foster City, CA, USA; 4 Cntr for Infectiology, Berlin, Germany; 5 Infektiologikum, Frankfurt/Main, Frankfurt, Germany; 6 Chelsea and Westminster Hosp NHS Fndn Trust, London, UK Background: There is no currently approved treatment for acute HCV infection. Guidelines recommend 24 weeks of therapy with interferon (IFN) and ribavirin in HIV coinfected individuals who are diagnosed with acute HCV. Shorter duration therapy with all-oral agents may offer a better-tolerated more efficacious alternative. Here we evaluated the safety, tolerability and efficacy of ledipasvir (LDV)/sofosbuvir (SOF) fixed dose combination for 6 weeks in genotype 1 or 4 HIV-infected patients with acute HCV infection. Methods: Patients with an acute HCV infection of <24 weeks duration as per NEAT AHC guidelines were included. Patients were required to either be receiving HIV antiretroviral (ARV) therapy with HIV RNA <200 copies/mL, or not be receiving any treatment for HIV with no plans to start therapy. Enrollment of patients with active illicit drug use was permitted. Patients with acute opportunistic infections or HBV co-infection were excluded. The primary endpoint was sustained viral response defined as HCV RNA. Results: Twenty-six patients were enrolled. All were male, the majority were Caucasian (92%), IL28B non-CC (54%), and receiving ARV therapy (96%). The median baseline HCV RNA was 5.4 log10 IU/mL. Nineteen (73%) patients had HCV genotype 1a infection and 7 (27%) had genotype 4 infection. All patients completed therapy. 22/26 (85%) achieved SVR4. Four (15%) patients relapsed. There was a strong relationship between baseline HCV RNA and treatment outcome (Figure). All patients (21/21) with baseline HCV RNA <9 million IU/mL achieved SVR4. Treatment was safe and well tolerated. Twenty two of 26 (85%) patients had an adverse event; the majority being mild or moderate. One patient had serious adverse events related to a motor vehicle accident and illicit drug use. No patients discontinued, died or experienced HIV rebound. Post treatment week 12 data will be presented. Conclusions: LDV/SOF for 6 weeks is effective and well tolerated in HIV-infected patients with acute HCV infection who have a baseline HCV RNA <9 million. Acutely HCV-infected patients with a higher viral load should be considered for longer duration of therapy.

Oral Abstracts

155 Empirical TB Treatment in Advanced HIV Disease: Results of the TB Fast Track Trial

Alison Grant 1 ; Salome Charalambous 2 ; MphoTlali 2 ; Suzanne Johnson 3 ; Susan Dorman 4 ; Christopher Hoffmann 4 ; Aaron Karat 1 ; AnnaVassall 1 ; Gavin Churchyard 2 ; Katherine L. Fielding 1 1 London Sch of Hygiene & Trop Med, London, UK; 2 The Aurum Inst, Johannesburg, South Africa; 3 Fndn for Professional Develop, Pretoria, South Africa; 4 Johns Hopkins Univ Sch of Med, Baltimore, MD, USA Background: Early mortality remains high among HIV-positive people starting ART; TB is the leading cause of death. We hypothesised that an algorithm designed for primary care nurses, using point-of-care tools to identify HIV+ people at high risk of TB, with rapid initiation of TB treatment, then ART, could reduce early mortality. We tested this management strategy in an open cluster-randomised trial, where clusters were South African primary care clinics. Methods: 24 primary care clinics were randomised 1:1 to intervention or control arms. We enrolled HIV+ adults with CD4≤150, not taking ART or TB treatment. In the intervention arm, study nurses categorised participants’ TB probability as high (any of Hb <10g/dl, body mass index ≤18.5 or a positive lateral flow assay for urinary lipoarabinomannan), medium (any TB symptom, no high probability criteria) or low (no TB symptoms or high probability criteria). If high probability, participants started TB treatment immediately, then ART two weeks later; if medium probability, further TB investigations were arranged, with re-assessment within a week; if low probability, ART was initiated. The primary outcome was all-cause mortality at 6 months; secondary outcomes included the 6-month risk of hospitalisation. Analyses used methods appropriate for cluster-randomised trials with a small number of clusters. The study is complete: the primary outcome results are final. Results: 3030 participants (55% female, median age 37 years, median CD4 72 cell/mm 3 ) were included in the analysis (intervention: 1508; control: 1522). In the intervention arm, 45.7%, 31.5% and 22.8%were categorised as high, medium and low priority respectively. At 6 months, 98.6% (intervention) vs 97.7% (control) had known vital status: mortality rate was 19.0 (intervention) vs. 21.5 (control) per 100 pyrs; adjusted rate ratio 0.87 (95% CI 0.61, 1.24). By 6 months, 13.9% (intervention) vs 10.8% (control) participants had been hospitalised at least once (adjusted risk ratio [aRR] 1.14, 95% CI 0.74, 1.74), and 16.6% (intervention) vs 15.1% (control) participants had been hospitalised and/or had died (aRR 1.01 (95%CI 0.80, 1.28). Conclusions: A management strategy prioritising TB treatment for ambulatory HIV+ individuals at high risk of TB did not reduce mortality or the risk of hospitalisation by 6 months. Further work is needed to identify strategies to reduce early mortality among HIV+ people presenting for ART with low CD4 counts.

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CROI 2016