CROI 2018 Abstract eBook

Abstract eBook

Oral Abstracts

based screening as a replacement for TST-based screening. There is little data on the effectiveness of this recommendation. Methods: A cluster-randomized trial was conducted to determine whether symptom-based screening improved the proportion of identified child contacts < 5 years who initiated IPT compared to TST-based screening clinics. From October 2015 through February 2017 in the Matlosana sub-district of North West Province, 16 clinics were randomized to conduct child contact evaluations with either symptom-based or TST- based screening. Training and customized child contact management files were provided to all clinics. Outcome data were abstracted from clinical records. Cluster adjusted results are shown. Results: Clinic-based tracing identified 547 and 464 children <5 from 1440 and 1597 TB index patients in the symptom-based and TST-based testing clinics, respectively (0.37 vs 0.28 per case; p=0.17). Of these identified contacts, 52% and 57% initiated IPT from the symptom and TST-based screening groups, (p=0.53) and 31% and 40% of children who started IPT more than 7 months previously completed therapy (p=0.36). Three (0.8%) children were not diagnosed with TB by symptom-based screening, requiring a change from IPT to TB treatment. There were no child deaths. Based on an historic average of 0.7 child contacts per index case in Matlosana, we estimate 30% and 25% IPT coverage among child contacts exposed to TB by symptom-based and TST-based screening respectively (p=0.54). Conclusion: TB nurses in decentralized clinics appropriately initiated IPT using symptom-based screening. However, symptom- based screening did not improve the proportion of identified child contacts initiated on IPT when compared to TST-based screening. Further research is needed to identify bottlenecks and evaluate interventions to ensure all TB-exposed children <5 receive TB preventive therapy.

daily during and for 2 weeks post-TB therapy, followed by 50mg once daily [OD]) or EFV (600mg OD), with 2 investigator-selected NRTIs for 52 weeks. For this Week 24 interim analysis, the proportion of subjects with plasma HIV-1-RNA <50 c/mL was derived using the FDA Snapshot algorithm in the intent to treat exposed (ITT-E) population. Safety was assessed in all subjects who received study drug. An independent committee adjudicated IRIS episodes. The study was not powered to show a difference between study arms; no formal statistical hypothesis was tested. Results: Of 113 subjects enrolled, 69 were randomised to DTG and 44 to EFV. Median baseline HIV-1 RNA and CD4+ cell counts were 5.10 log 10 c/mL and 208 cells/µL in the DTG arm and 5.24 log 10 c/mL and 202 cells/µL in the EFV arm; 40%were women. The proportions of subjects with HIV-1-RNA <50 c/mL at Week 24 were 56/69 (81%) (95% CI: 72%, 90%) in the DTG arm and 39/44 (89%) (95% CI: 79%, 98%) in the EFV arm. The lower DTG response rate was driven by non-treatment related snapshot failures: five participants (7%) in DTG arm and none in EFV arm discontinued due to non-treatment-related reasons (loss to follow-up/protocol deviations). Median CD4+ cell increases at Week 24 were 146 cells/µL (IQR: 71, 214) for DTG and 93 cells/µL (IQR: 47, 178) for EFV. Two subjects discontinued study treatment due to AEs (both on EFV). TB-Associated IRIS rates (adjudicated and investigator reported) were low (DTG, n=4 [6%]; EFV, n=4 [9%]). No subjects discontinued due to IRIS or liver events. Conclusion: InterimWeek 24 results from this ongoing study show that DTG 50 mg twice daily appears to be effective and well-tolerated in HIV/TB co-infected adults receiving RIF-based TB therapy. Rates of IRIS were low. There were no new toxicity signals for DTG and no discontinuations due to liver events. These data support the use of DTG based regimen in HIV/TB co-infection. 34 PHARMACOKINETICS OF BICTEGRAVIR ADMINISTERED TWICE DAILY IN COMBINATION WITH RIFAMPIN Joseph M. Custodio , Steve K. West, Sean Collins, Amanda Vu, Deqing Xiao, Hal Martin, Erin Quirk, Brian P. Kearney, Anita Mathias Gilead Sciences, Inc, Foster City, CA, USA Background: Bictegravir (BIC; B) is a potent, once-daily, unboosted HIV integrase strand transfer inhibitor (INSTI) with a high barrier to resistance. BIC is coformulated with the NRTI backbone of emtricitabine/tenofovir alafenamide (F/TAF) into the single-tablet regimen, B/F/TAF for treatment of HIV-1 infection. BIC is primarily hepatically eliminated, with similar contributions by the drug metabolizing enzymes CYP3A and UGT1A1. Rifampin (RIF), a component of tuberculosis (TB) treatment, is a potent inducer of metabolizing enzymes. A previous study evaluating the coadministration of RIF with once-daily BIC showed a marked reduction in BIC concentrations. The present study evaluated the pharmacokinetics (PK) of BIC administered twice daily (BID) in combination with RIF. Methods: Healthy subjects were enrolled into one of two cohorts (N=26/ cohort). Cohort 1 subjects received B/F/TAF (50/200/25 mg) QD, 2 hours postprandial, for 28 days. Cohort 2 subjects received B/F/TAF BID plus RIF 600 mg QD, 2 hours postprandial, for 28 days. Intensive plasma sampling was conducted on Day 28 for determination of BIC primary PK parameters (AUC 0-24h , C max , C trough ). Statistical comparisons for BIC were performed using geometric least squares mean (GLSM) ratios and associated 90% confidence intervals (CI) with B/F/TAF BID plus RIF in Cohort 2 as the test treatment and B/F/TAF QD in Cohort 1 as the reference treatment. Safety was assessed throughout the study and follow up. Results: Following coadministration of B/F/TAF BID plus RIF for 28 days, the BIC AUC 0-24h and C max were decreased approximately 61% and approximately 47%, respectively, as compared with B/F/TAF QD administration alone (Table 1). Although the observed BIC C trough in all subjects was above the protein adjusted 95% effective concentration (paEC 95 ) (162 ng/mL) following B/F/TAF BID plus RIF in Cohort 2, the resulting geometric least squares mean BIC C trough was approximately 80% lower, as compared with that observed following B/F/ TAF QD in Cohort 1 (Table 1). All treatments were well tolerated and all subjects completed the study. Conclusion: The present study results confirm the drug drug interaction between RIF and BIC. These findings show that twice daily administration of B/F/TAF with RIF does not mitigate the induction effect sufficiently to yield BIC C trough concentrations associated with the B/F/TAF registrational Phase 3 studies.

Oral Abstracts

33 SAFETY AND EFFICACY OF DOLUTEGRAVIR-BASED ART IN TB/HIV COINFECTED ADULTS AT WEEK 24 Kelly Dooley 1 , Richard Kaplan 2 , Noluthando Mwelase 3 , Beatriz Grinsztejn 4 , Eduardo Ticona 5 , Marcus Lacerda 6 , Pedro Cahn 7 , Elena Belonosova 8 , Mounir Ait-Khaled 9 , Kostas Angelis 10 , Dannae Brown 9 , Rajendra P. Singh 11 , Christine Talarico 12 , Allan-Raymond Tenorio 12 , Michael Aboud 9 1 Johns Hopkins University, Baltimore, MD, USA, 2 Desmond Tutu HIV Foundation, Cape Town, South Africa, 3 Clinical HIV Research Unit, Johannesburg, South Africa, 4 Oswaldo Cruz Foundation - Fiocruz, Rio de Janeiro, Brazil, 5 Hospital Nacional Dos de Mayo, Lima, Peru, 6 Fiocruz, Manaus, Brazil, 7 Fundación Huésped, Buenos Aires, Argentina, 8 Orel Regional Center for Prevention and Treatment of AIDS and Infectious Diseases, Orel, Russian Federation, 9 ViiV Healthcare, Brentford, UK, 10 GlaxoSmithKline, Uxbridge, UK, 11 GlaxoSmithKline, King of Prussia, PA, USA, 12 ViiV Healthcare, Research Triangle Park, NC, USA Background: Concurrent treatment of TB and HIV is compounded by drug interactions, overlapping toxicities, and immune reconstitution inflammatory syndrome (IRIS). The efficacy and safety of dolutegravir (DTG) in antiretroviral treatment (ART) naïve adults with HIV/TB co-infection was assessed. Methods: INSPIRING (NCT02178592) is a Phase 3b, non-comparative, active control, randomised, open-label study in HIV-1 infected ART-naïve adults (CD4+≥50 cells/µL) with drug-sensitive TB. Participants on rifampin-based TB treatment for up to 8 weeks were randomised (3:2) to receive DTG (50mg twice

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CROI 2018