CROI 2015 Program and Abstracts

Abstract Listing

Oral Abstracts

114LB Antiviral Activity/Safety of a Second-Generation HIV-1 Maturation Inhibitor Carey Hwang 1 ; Dirk Schürmann 2 ; Christian Sobotha 2 ; Heather Sevinsky 1 ; Palanikumar Ravindran 1 ; Hong Xiao 1 ; Neelanjana Ray 1 ; Mark Krystal 3 ; Ira B. Dicker 3 ; Max Lataillade 3 1 Bristol-Myers Squibb, Princeton, NJ, US; 2 Charité Research Organisation GmbH, Berlin, Germany; 3 Bristol-Myers Squibb, Wallingford, CT, US Background: BMS-955176 is a 2 nd -generation HIV-1 maturation inhibitor (MI). A 1 st generation MI (bevirimat) showed clinical efficacy in early-phase studies, but ~50% of subjects had reduced viral susceptibility associated with naturally occurring polymorphisms in Gag. We assessed BMS-955176 antiviral activity, safety, and exposure–response during 10 days of monotherapy in HIV-1, subtype B-infected subjects. Methods: AI468002 (NCT01803074) is a Phase 2a, randomized, multi-part trial. Forty HIV-1, subtype B-infected subjects with HIV-1 RNA ≥ 5000 c/mL and CD4+ T-cell counts ≥ 200 cells/ m L were randomized 1:1:1:1 to BMS-955176 dose groups of 5, 10, 20 or 40 mg, then 4:1 to receive an oral suspension of BMS-955176 or placebo once daily (QD) for 10 days. Twenty additional subjects were later randomized to 80 and 120 mg QD dose groups. The primary endpoint was change in HIV-1 RNA from baseline to Day 11; safety and exposure– response were secondary endpoints. Results: Overall, 60 subjects were randomized to receive either BMS-955176 (n=48) or placebo (n=12). Median change in HIV-1 RNA from baseline to Day 11 ranged from − 0.15 to − 1.36 log 10 c/mL and maximummedian change between baseline and Day 24 (study discharge) ranged from − 0.50 to − 1.70 log 10 c/mLacross the BMS-955176 groups. An exposure–response relationship was observed; there was an increase in maximummedian response over the range of 5–40 mg QD, which plateaued at ~–1.64 log 10 c/mL at doses of 40–120 mg QD. Maximummedian declines in HIV-1 RNA were similar for the 40–120 mg QD dose groups regardless of baseline Gag polymorphisms (positions evaluated: V362, Q369, V370, and T371). BMS-955176 was generally well tolerated at all doses. There were no deaths, serious adverse events (SAEs), AEs leading to discontinuation, grade 3–4 c/mL in the 40 mg group. Unlike 1 st - generation MIs, in this proof-of-concept study BMS-955176 showed similar antiviral activity in subjects with wild-type HIV-1 or HIV-1 with Gag polymorphisms. BMS-955176 was generally well tolerated at all doses. Phase 2b studies for BMS-955176 will begin Q2, 2015. 115LB Early ART and IPT in HIV-Infected African Adults With High CD4 Count (Temprano Trial) Christine Danel 1 ; Raoul Moh 2 ; Delphine Gabillard 1 ; Anani Badje 4 ; Jerome Le Carrou 1 ; Gerard M. Kouame 4 ; Jean Baptiste Ntakpe 4 ; Hervé Ménan 3 ; Serge Eholie 2 ; Xavier Anglaret 1 On behalf of theTemprano Study Group 1 Inserm, Bordeaux, France; 2 Université Felix Houphouet Boigny, Abidjan, Côte d’Ivoire; 3 CHU de Treichville, Abidjan, Côte d’Ivoire; 4 Programme PACCI, Abidjan, Côte d’Ivoire Background: We present the final results of the Temprano ANRS 12136 trial that assessed the benefits of early ART and/or early 6-month isoniazid prophylaxis (IPT, 300 mg/day) among HIV-infected adults with high CD4 counts and no WHO criteria for starting ART. Methods: Temprano was a randomized 2x2 factorial superiority trial conducted in 9 HIV care centers in Côte d’Ivoire fromMarch 2008 through January 2015. Inclusion criteria were: HIV-1 infection, age >18 years, CD4 nadir <800/ul, and no criteria for starting ART according to the most recent WHO guidelines. Participants were randomized to one of four arms: ART initiation according to WHO criteria (WHOART); immediate 6-month IPT plus ART initiation according to WHO criteria (WHOART-IPT); immediate ART initiation (EarlyART); immediate 6-month IPT plus immediate ART initiation (EarlyART-IPT). First-line ART consisted of tenofovir plus emtricitabine plus either efavirenz, zidovudine or lopinavir/ritonavir. The primary endpoint was severe HIV morbidity (AIDS-defining diseases, non-AIDS-defining malignancy, or non-AIDS-defining invasive bacterial diseases),or any-cause mortality at 30 months. The secondary endpoint was any other grade 3-4 defining morbidity. We used multivariate Cox proportional models to compare outcomes between the WHOART and EarlyART arms, and between the IPT and no IPT arms. We tested for interaction between earlyART and IPT. Results: Of 2,076 patients randomized, 2,056 were included in the analysis (78%were women; 91% classified at WHO stage 1-2; median age 35 years; median CD4 nadir 465/ul; median HIV-1 viral load 4.7 log 10 copies/ml). They were followed for 4,755 patient-years, during which 47 died, 175 experienced 204 episodes of severe morbidity (TB 85, invasive bacterial diseases 56, other AIDS-defining diseases 11, non-AIDS malignancy 5), 287 experienced 364 episodes of severe grade 3-4 morbidity (hematologic 256, hepatic 31 renal, 22, cardiovascular 9, others 46), and 44 (2.2%) were lost-to-follow up. There was no interaction between EarlyART and IPT. The risk of severe morbidity was 44% lower with EarlyART vs. WHOART (Table) and 35% lower with IPT vs. no IPT. EarlyART significantly decreased morbidity overall and when restricted to patients with baseline CD4 >500/ul. The risk of Grade 3-4 morbidity did not differ between strategies. related AEs or clinically relevant grade 2–4 laboratory abnormalities. Conclusions: BMS-955176 achieved maximummedian declines of >1 log 10 c/mL in HIV-1 RNA at doses of 20–120 mg QD. Response increased with doses up to 40 mg QD, with a plateau of ~–1.64 log 10 c/mL observed at 40–120 mg QD. The greatest response achieved was a maximummedian change of –1.70 log 10

Oral Abstracts

Conclusions: In Côte d’Ivoire, both immediate ART and IPT dramatically and independently decreased the risk of severe morbidity, and should be recommended as the standard of care for HIV. 116 Antiretroviral Drug Screening Provides Key Insights Into HIV Drug Resistance Iris Chen 1 ; Matthew B. Connor 2 ;William Clarke 1 ; Mark A. Marzinke 1 ;Vanessa Cummings 1 ; Sheldon D. Fields 3 ; Darrell P.Wheeler 4 ; Kenneth H. Mayer 5 ; Beryl A. Koblin 6 ; Susan H. Eshleman 1 1 Johns Hopkins University School of Medicine, Baltimore, MD, US; 2 Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA, US; 3 Florida International University, Miami, FL, US; 4 Loyola University Chicago, Chicago, IL, US; 5 Fenway Health, Boston, MA, US; 6 New York Blood Center, New York, NY, US Background: The HIV Prevention Trials Network (HPTN) 061 study enrolled HIV-infected and HIV-uninfected Black men who have sex with men in six cities in the United States who were at a high risk of HIV infection. Most of the HIV-infected men in the study reported that they were unaware of their HIV status or that they were aware of their status but were not in care. HIV drug resistance was detected in 48 (28.4%) of 169 HIV-infected men who were not virally suppressed at study enrollment. We used a high-throughput assay to screen for the presence of antiretroviral (ARV) drugs in samples from these study participants.

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CROI 2015