CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

Methods: Whole blood from symptomatic people living with HIV (PLHIV) in South Africa were collected from February 2016 to August 2017 and biobanked in PAXgene tubes. The accuracy of the Xpert Prototype on these biobanked samples was compared against a comprehensive microbiological reference standard (culture and Xpert® MTB/RIF). The performance was also compared against Xpert® MTB/RIF alone, as Xpert will be the most likely confirmatory assay used in programmatic settings in high-burden countries. We depict results in ROC curves and for pre-set cut-points based on performance targets set for a triage test by the World Health Organization. Results: Of the 201 patients included, 67 were culture-positive. At a cut-point chosen to maximize the Youden index, sensitivity was 77.6% (95% Confidence Interval [CI] 66.3–85.9), specificity was 92.2% (CI 86.3–95.7) and the AUC was 0.89 (CI 0.83-0.94) against the comprehensive reference standard. Considering the Xpert-Prototype as a triage test (fixed sensitivity value closest to 90%), the corresponding specificity was 55.8% (CI 47.2-64.1). Comparing to Xpert® MTB/RIF alone as a confirmatory test at fixed value of sensitivity closest to 90% (90.6%), the Xpert Prototype specificity was 85.9% (CI 79.3-90.7). Considering the Xpert Prototype as a stand-alone diagnostic test, at a specificity of 95%, the test achieves a sensitivity of 65.7% (CI 53.7-75.9). Conclusion: In this first accuracy study of a novel blood-based host-marker assay on a commercial platform, we show the possible value of the assay for triage and potentially also for diagnosis, when a sputum sample is difficult to obtain, as often the case in PLHIV.

88.2%, 95%CI 77.6-96.7; sensitivity 87.5%, 95%CI 57.1-95.8; specificity 65.8%, 95%CI 62.4-69). Nine cases of incident TB were identified through median 15 months follow- up; incidence was 2.5% in RISK11+ vs 0.2% in RISK11- participants (RISK11 cumulative incidence ratio, CIR 16.6, 95%CI 2.1-133.9; AUC 80.1%, 95%CI 70.7- 87.1; sensitivity 88.9%, 95%CI 44.5-98.8; specificity 69.1%, 95%CI 65.3-72.5). TB incidence was 1.6% in QFT+ vs 0.7% in QFT- participants (QFT CIR 2.3, 95%CI 0.6-9.3; AUC 72.6%, 95%CI 57.8-83.7; sensitivity 65.8%, 95%CI 30.5-89.5; specificity 56.1%, 95%CI 52.3-59.9). Conclusion: RISK11 screening identified ambulant HIV+ adults with prevalent TB and predicted risk of progressing to active TB within 15 months. RISK11 performance approaches the WHO screening (sensitivity 90%; specificity 70%) and predictive (sensitivity and specificity 75%) test target product profiles (TPP) among HIV+ adults at the pre-specified score threshold. QFT performance falls short of the predictive TPP. RISK11 translation to a point-of-care assay may allow early identification of HIV+ adults that would benefit from further TB testing, therapy, or intensified follow-up. 763 A NOVEL PHARMACOLOGICAL ADHERENCE MEASURE IN PREGNANT AND POSTPARTUM KENYAN WOMEN Karen Hampanda 1 , Jose R. Castillo-Mancilla 1 , Janet M. Turan 2 , Maricianah Onono 3 , Tobias Odwar 4 , Peter L. Anderson 1 , Lisa L. Abuogi 1 1 University of Colorado Anschutz Medical Campus, Aurora, CO, USA, 2 University of Alabama at Birmingham, Birmingham, AL, USA, 3 Kenya Medical Research Institute, Nairobi, Kenya, 4 KEMRI-UCSF, Kisumu, Kenya Background: Antiretroviral therapy (ART) adherence among pregnant and postpartumwomen with HIV (PWHIV) is critical to promote maternal health and prevent HIV transmission. Tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) is an objective assessment of long-term drug exposure and adherence that is associated with viral suppression. Tenovofir disoproxil fumarate (TDF) is part of the first-line regimen for PWHIV in Kenya, providing the opportunity to quantify ART adherence with this novel biomarker. Methods: 150 PWHIV receiving TDF-based ART regimens for a minimum of 10 weeks recruited from 24 health facilities in southwestern Kenya provided DBS samples at three time points (pregnancy/early postpartum (PP), 6 months PP, and 9-12 months PP). DBS were analyzed using validated laboratory testing. Results: 419 DBS samples were collected. Median (IQR) TFV-DP at baseline (pregnancy/early PP), 6 months PP, and 9-12 months PP was: 885 (635, 1172), 851 (608, 1132), and 811 (519,1012) fmol/punch, respectively. TFV-DP ≥1250 fmol/ punch (threshold for daily adherence in healthy US volunteers) was detected in only 11% at baseline and decreased to <6% in both the PP time periods. Using a more conservative estimate of adherence, TFV-DP ≥700 fmol/punch (threshold for ≥4 doses/week in healthy US volunteers), adequate adherence was detected in 68%, 65% and 60% of PWHIV at baseline, 6 months PP and 9-12 months PP, respectively. We identified four discrete adherence trajectories in PWHIV (Figure): those whose TFV-DP level consistently decreased across the PP period (19%); those whose TFV-DP level consistently increased across PP (15%); those who improved initially but then worsened (35%); and those who worsened initially but then improved (30%). Those with consistently decreasing TFV-DP had the lowest median late PP adherence results (577 fmol/punch). Conclusion: Cumulative ART exposure in PWHIV, quantified by TFV-DP in DBS, demonstrated a trend towards decreased concentrations (i.e., adherence) over time from pregnancy into the PP period. Over half of PWHIV show decreasing adherence postpartum. This raises concern for higher likelihood of poor adherence and viremia in the critical PP period during breastfeeding. The use of TFV-DP in DBS as a measure of ART adherence in PWHIV in sub-Saharan Africa could be an important tool to optimize health outcomes.

Poster Abstracts

762LB PROSPECTIVE VALIDATION OF A BLOOD RNA TB BIOMARKER IN AMBULANT HIV-INFECTED ADULTS

Simon C. Mendelsohn 1 , Andrew Fiore-Gartland 2 , Adam Penn-Nicholson 1 , Humphrey Mulenga 1 , Chris Hikuam 1 , Katie Hadley 1 , Michele Tameris 1 , Craig Innes 3 , William L. Brumskine 3 , Gerhard Walzl 4 , Kogieleum Naidoo 5 , Gavin Churchyard 3 , Thomas J. Scriba 1 , Mark Hatherill 1 , for the CORTIS-HR Study Team 1 University of Cape Town, Cape Town, South Africa, 2 Fred Hutchinson Cancer Research Center, Seattle, WA, USA, 3 The Aurum Institute, Johannesburg, South Africa, 4 Stellenbosch University, Cape Town, South Africa, 5 CAPRISA, Durban, South Africa Background: New non-sputum tuberculosis (TB) biomarkers for predicting progression to active TB disease are needed to achieve the goals of the WHO End TB Strategy. We previously developed and validated a blood transcriptomic correlate of risk, RISK11, that identified individuals with active TB or high risk of progression to active TB in case-control studies. This study aimed to test diagnostic and predictive RISK11 performance for prospective community- based TB screening in HIV+ individuals, and to compare predictive performance with QuantiFERON-TB Gold Plus (QFT). Methods: Ambulant HIV+ adults were enrolled across 5 sites in South Africa. ART naïve participants were referred for ART and isoniazid preventive therapy per country guidelines. RISK11 status was assessed at baseline and was double-blinded; RISK11 positivity was pre-defined at 60% score threshold. Participants were assessed at enrollment and underwent active surveillance for microbiologically-confirmed TB for up to 15 months. Here we report preliminary results. Results: Among 861 participants (median age 35; 72% female; 11% symptom+; 78% ART experienced with median ART duration 3 years; median CD4 count 529 [IQR 350-725]), 33.1%were RISK11+ and 45.6% QFT+. Ten cases of TB were identified at baseline; prevalence was 2.5% in RISK11+ vs 0.2% in RISK11- participants (diagnostic risk ratio 13.1, 95%CI 2.1-81.6; AUC

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