CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

Methods: Phase 2b, multicentre, partially-blinded dose-ranging study in ART-naïve HIV infected adults, randomized 1:1:1:1 to the induction regimen of once daily oral CAB 10, 30, or 60 mg or efavirenz (EFV) 600 mg with TDF/FTC or ABC/3TC through W24. CAB patients (Pts) with VL <50 c/mL immediately prior to W24 discontinued NRTIs and began RPV 25 mg as a two drug oral maintenance regimen through W96. No change was made to the EFV arm. After W96, at the start of the open-label (OL) phase, all Pts randomized to CAB were given the option to continue on the sponsor selected dose (30 mg) of CAB. EFV arm Pts completed the study at W96. The OL phase is ongoing and CAB Pts have completed W144, 120 weeks on a two-drug ART regimen as of this analysis. Results: 243 Pts were randomized and initiated treatment (ITT-E). Of those randomized to CAB (n=181), 160 Pts began the maintenance regimen (W24) and138 continued into OL phase (W96). Amongst Pts who began CAB + RPV at W24, 76%maintained <50 c/mL, and 8%were virologic non-responders by Snapshot at W144 (ITT-ME). There were 9 protocol defined virologic failures (PDVF) on CAB, 3 occurred after W96. One Pt developed treatment emergent (TE) NNRTI resistance mutations at W132. No Pts developed TE major INI resistance mutations since W96. In total, 5 Pts developed TE resistance to one or both agents during the study. During the maintenance and OL phases, 7 (4%) reported drug- related AEs ≥ Grade 2. SAEs occurred in 15 (9%) CAB Pts (none drug related) and 4 (3%) withdrew due to AEs. Maintenance TE maximum lab abnormalities ≥ Grade 3 occurred in 25% of CAB Pts, with lipase and creatine kinase only having ≥5% of Pts (5% and 9% respectively). 17% of CAB Pts had a maintenance TE graded ALT, <1%were ≥ Grade 3. Conclusion: As maintenance therapy in virologically suppressed Pts, the two drug regimen CAB + RPV provided durable viral suppression through W144. CAB + RPV continues to be generally safe and well tolerated; these data support progression to phase 3 studies. 443 EFFICACY & SAFETY OF SWITCHING TO EVG/COBI/FTC/TAF IN VIROLOGICALLY SUPPRESSED WOMEN Sally Hodder 1 , Kathleen Squires 2 , Cissy Kityo 3 , Debbie Hagins 4 , Anchalee Avihingsanon 5 , Yulia Plotnikova 6 , Shuping Jiang 7 , Rima Kulkarni 7 , Andrew Cheng 7 , Huyen Cao 7 1 West Virginia Clinical and Translational Sci Inst, Morgantown, WV, USA, 2 Thomas Jefferson Univ, Philadelphia, PA, USA, 3 Joint Clinical Rsr Cntr, Kampala, Uganda, 4 Chatham CARE Cntr, Savannah, GA, USA, 5 HIV-NAT, Thai Red Cross AIDS Rsr Cntr, Bangkok, Thailand, 6 Irkutsk Regional Cntr for Prevention and Control of AIDS and Infectious Diseases, Irkutsk, Russian Federation, 7 Gilead Scis, Inc, Foster City, CA, USA Background: The integrase inhibitor regimen (elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate [E/C/F/TDF]) demonstrated superior efficacy when compared to a protease inhibitor regimen (atazanavir boosted by ritonavir [ATV/r] plus F/TDF) in 575 treatment naïve women at Week (W) 48. We now report the safety and efficacy of subsequent switching to E/C/F/tenofovir alafenamide (TAF) versus remaining on ATV/r+F/TDF. Methods: After completing the initial randomized, blinded 48-week trial, women on ATV/r+F/TDF were randomized 3:1 to receive open label E/C/F/TAF versus remaining on their current regimen. Viral suppression (HIV-1 RNA <50 and <20 copies [c]/mL) by FDA snapshot analysis, pre-defined bone and renal safety, and tolerability endpoints 48 weeks after switch are reported. Women who become pregnant while on study are given the option to continue study drug. Results: 212 HIV-infected, virologically suppressed women were randomized (E/C/F/TAF n=159, ATV/r+F/TDF n=53). Virologic suppression (<50 c/mL) was maintained in 94.3% on E/C/F/TAF vs 86.8% on ATV/r+F/TDF (weighted difference: 7.5%; 95% CI: -1.2% to 19.4%), with virologic failure in 1.9%, 3.8%, respectively. More women on E/C/F/ TAF achieved <20 c/mL at W48 compared to ATV/r+F/TDF (84.9% versus 71.7%, weighted difference: 13.2% [-0.0% to 27.5%], p=0.041). No treatment emergent resistance was detected in either study groups. Mean % increase in BMD was higher in the TAF group for both lumbar spine and total hip (Table). Multiple markers of renal safety were improved for participants randomized to TAF (Table). No cases of proximal renal tubulopathy were reported. Participants on TAF had greater increases in lipids (Table), with no difference in TC:HDL ratio (Table). 19 women became pregnant during the switch study, 13 E/C/F/TAF and 6 ATV/r+F/TDF) and 3 normal infants have been delivered in each group to date. Conclusion: These data demonstrate that women who switch to an integrase inhibitor + TAF-based regimen maintain high levels of virologic suppression with improvement in BMD and renal function biomarkers, as compared with those remaining on their ritonavir boosted atazanavir+TDF-based regimen.

Poster and Themed Discussion Abstracts

444 THE FDA SNAPSHOT ALGORITHM MAY OVERESTIMATE THE EFFICACY OF INITIAL ART Stephen J. Kerr 1 , Andrew Carr 2 1 The Thai Red Cross AIDS Rsr Cntr, Bangkok, Thailand, 2 St. Vincent’s Hosp, Sydney, Australia Background: The FDA Snapshot algorithm defines success of antiretroviral therapy (ART) by viral load < 50 cp/mL without ART change (mostly for adverse events [AEs]). Notably, a viral load <50 cp/mL but with a drug-related AE is regarded as treatment success. However, drug-related AEs might increase the risk of ART failure. Methods: We hypothesised that an efficacy algorithm incorporating ART-related AEs would be clinically meaningful, as they would predict ART failure. We analysed individual- patient data from SINGLE, a placebo-controlled trial of abacavir-lamivudine-dolutegravir (ABC-3TC-DTG) vs. tenofovir-emtricitabine-efavirenz (TDF-FTC-EFV). Data were obtained via clinicalstudydatarequest.com/ after independent protocol review by the Wellcome Trust (but not the study sponsor). We investigated if drug-related AEs through Week 12 predicted subsequent ART failure, and failure rates using the Snapshot algorithm vs. a ‘Snapshot-Plus’ algorithm that additionally regards Grade-2+ drug-related AEs as ART failure. Groups were compared through Week 144, as were strata ≥ or <100,000 cp/mL at baseline. Data were analysed by calculating the proportion of responders (95%CI) with both algorithms. Chi-square and McNemar tests compared responders within and between algorithms, respectively. Logistic regression determined the odds of failure by the Snapshot algorithm for subjects experiencing drug-related AEs to week 12.

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