CROI 2018 Abstract eBook

Abstract eBook

Oral Abstracts

30LB RESULTS OF ACTG A5288: A STRATEGY STUDY IN RLS FOR 3 RD -LINE ART CANDIDATES Beatriz Grinsztejn 1 , Michael D. Hughes 2 , Justin Ritz 2 , Robert Salata 3 , Peter Mugyenyi 4 , Evelyn Hogg 5 , Linda Wieclaw 6 , Robert Gross 7 , Catherine Godfrey 8 , Nagalingeswaran Kumarasamy 9 , Cecilia Kanyama 10 , John W. Mellors 11 , Carole Wallis 12 , Ann Collier 13 1 Instituto Nacional de Infectologia Evandro Chagas, Rio de Janeiro. Brazil, 2 Harvard University, Boston, MA, USA, 3 Case Western Reserve University, Cleveland, OH, USA, 4 Joint Clinical Research Centre, Kampala, Uganda, 5 Social & Scientific Systems, Silver Spring, MD, USA, 6 Frontier Science & Technology Research Foundation, Inc, Amherst, NY, USA, 7 University of Pennsylvania, Philadelphia, PA, USA, 8 NIAID, Bethesda, MD, USA, 9 YR Gaitonde Center for AIDS Research and Education, Chennai, India, 10 University of North Carolina Project–Malawi, Lilongwe, Malawi, 11 University of Pittsburgh, Pittsburgh, PA, USA, 12 Lancet Labs and BARC SA, Johannesburg, South Africa, 13 University of Washington, Seattle, WA, USA Background: Individuals presenting for 3rd line ART are a challenge in resource limited settings (RLS) because of uncertain ARV susceptibility and limited data on virologic responses to remaining available ARV regimens. Methods: A5288 is an open-label strategy study in RLS in HIV-1 infected individuals presenting with confirmed plasma HIV RNA (VL) ≥ 1000 copies after > 24 weeks of protease-based (PI) 2nd line ART. Primary objective was to use novel antiretrovirals and contemporary management tools, including standard genotyping to select an appropriate 3rd-line regimen, interventions to improve adherence, and VL monitoring, to achieve virologic suppression in ≥65% at 48 weeks of follow-up. Review of prior ART, combined with real-time standard genotype, determined Cohort A-D assignment (Table). An exploratory randomized comparison in Cohort B of NRTIs+DRV/r+RAL (B1) versus ETR+DRV/ r+RAL (B2) among HBV Ab- participants was performed; HBV Ab+ participants in B received DRV/r + RAL + TDF/FTC or TDF+3TC (B3). Suppression of VL ≤200 copies/mL at 48 weeks and virologic failure (VF, two consecutive ≥1000 copies/ mL ≥ 24 weeks) were 1o and 2o endpoints. Results: From 2013-2015, 545 participants in 10 countries in Africa, Asia, South America and the Caribbean enrolled: 47% females; median age 41 years, median CD4 count 175 cells/mm 3 . At enrollment, drug resistance (moderate or high- level) to 0, 1, 2, and 3 ARV classes was identified in 22%, 20%, 30% and 27% of participants, respectively. Overall, 64% (95% CI 60, 68%) had VL ≤ 200 copies/ mL at week 48. Viral suppression and VF differed across cohorts (Table). By week 48, Cohort A had the most Grade ≥ 3 adverse events (39%) and regimen discontinuations (13%). No differences in VL ≤ 200 copies/mL at week 48 or VF ≥ 24 weeks were observed in the randomized comparison of B1 & B2 cohorts. Conclusion: Regimens containing DRV/r and RAL with or without ETR were highly effective for participants with LPV/r resistance who presented for 3rd line ART. More than half of participants without LPV/r resistance and who remained on 2nd line ART did not achieve viral suppression at week 48. This subgroup requires additional interventions to achieve viral suppression. Targeted real- time genotyping to select regimens for 3rd line ART can appropriately allocate more costly ARVs to those with greater resistance.

31 EFFECT OF TB SCREENING AND RETENTION INTERVENTIONS ON EARLY ART MORTALITY IN BOTSWANA Andrew F. Auld 1 , Tefera Agizew 2 , Anikie Mathoma 2 , Rosanna Boyd 2 , Anand Date 1 , Sherri Pals 1 , Christopher Serumola 2 , Unami Mathebula 2 , Heather Alexander 1 , Tedd V. Ellerbrock 1 , Goabaone Rankgoane-Pono 3 , Pontsho Pono 3 , Katherine Fielding 4 , Alison Grant 4 , Alyssa Finlay 2 1 CDC, Atlanta, GA, USA, 2 CDC Botswana, Gaborone, Botswana, 3 Ministry of Health, Gaborone, Botswana, 4 London School of Hygiene & Tropical Medicine, London, UK Background: In 2012, at 22 antiretroviral therapy (ART) clinics, Botswana implemented a phased rollout of the Xpert package of interventions, with 3 components: (1) additional nurses and mentoring to support intensified tuberculosis (TB) case finding (ICF) activities, (2) intensified tracing for patients missing clinic appointments, and (3) Xpert MTB/RIF (Xpert) replacing smear microscopy. We evaluated effect of the Xpert package on early (6- and 12- month) ART mortality in the XPRES trial (ClinicalTrials.gov: NCT02538952). Methods: At 22 ART clinics, all adult patients (>12 years old) starting ART were enrolled in three phases: (1) a retrospective standard of care (SOC) phase, (2) a prospective enhanced care (EC) phase, and (3) a prospective EC plus Xpert (EC+X) phase. EC and EC+X phases were enrolled as a stepped-wedge trial. Adults enrolled in the EC phase received SOC plus components 1 (TB ICF) and 2 (intensified tracing) of the Xpert package. Adults enrolled in the EC+X phase received SOC plus all 3 components of the Xpert package. All-cause 6-month ART mortality was the primary outcome. An adjusted analysis, appropriate for study design, controlled for baseline differences in individual-level factors and intra-facility correlation. Trial outcome results are final. Results: 14,963 eligible patients were enrolled; 8,980 in the SOC, 1,768 in the EC, and 4,215 in the EC+X phases. Median age of ART enrollees was 35 years, 64%were female, median weight was 58.4 kg, and median hemoglobin 11.7 g/dL. These characteristics were similar across phases. Pregnancy among females was less common in the SOC than subsequent phases (16% in SOC, 23% in EC, and 32% in EC+X). Median CD4 count at ART initiation was lower in SOC than subsequent phases (184/µL in SOC, 241/µL in EC, and 246/µL in EC+X). In adjusted analysis, compared with the SOC phase, 6-month ART mortality was significantly lower in the EC+X phase, while 12-month ART mortality was significantly lower in both the EC and EC+X phases (Table). When compared with the EC phase, 6- and 12-month mortality rates were not significantly different in the EC+X phase.

Oral Abstracts

Conclusion: In Botswana, interventions to strengthen TB ICF and active tracing were associated with lower early ART mortality and should be considered for scale-up. No additional mortality benefit of replacing smear microscopy with Xpert was observed.

32 A CLUSTER-RANDOMIZED TRIAL OF SYMPTOM VS TST SCREENING TO IMPROVE CHILD IPT UPTAKE Nicole Salazar-Austin 1 , Silvia Cohn 1 , Grace Barnes 1 , Molefi Tladi 2 , Katlego Matlhaoleng 2 , Catharina Swanepoel 3 , Zarina Motala 3 , Ebrahim Variava 4 , Neil A. Martinson 2 , Richard E. Chaisson 1 1 Johns Hopkins Hospital, Baltimore, MD, USA, 2 Perinatal HIV Research Unit, Soweto, South Africa, 3 Matlosana Department of Health, Klerksdorp, South Africa, 4 Klerksdorp Tshepong Hospital Complex, Jouberton, South Africa Background: HIV and tuberculosis (TB) disproportionately affect women of reproductive age in sub-Saharan Africa, resulting in increased household TB exposure of HIV-infected and HIV-exposed children. Isoniazid preventive therapy (IPT) is highly-effective at preventing tuberculosis (TB) disease in children < 5 years. IPT implementation has been hampered by health system, provider and patient challenges. In 2006, the WHO recommended symptom-

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CROI 2018