CROI 2015 Program and Abstracts

Abstract Listing

Oral Abstracts

34 Evaluation of the Alere q for Point-of-Care Early Infant HIV Diagnosis in South Africa Nei-Yuan Hsiao 1 ; Max Kroon 2 ; Lorna Dunning 2 ; Landon Myer 2 1 University of Cape Town, Cape Town, South Africa; 2 University of Cape Town, Cape Town, South Africa

Background: New point-of-care (POC) HIV molecular diagnostic tools could fundamentally alter early infant HIV diagnosis (EID) and management in resource-limited settings by reducing the time to initiation of antiretroviral therapy and promoting retention in care. However few technologies have been independently evaluated and data on new technologies are urgently required. Methods: We investigated the analytic performance of the Alere q HIV1/2 POC assay in the laboratory setting by comparing the result with the local standard-of-care (SOC), Roche CAP/CTM HIV-1 qualitative PCR. Testing was conducted on routinely collected EID samples received at the public sector reference lab in Cape Town, South Africa between November 2013 and September 2014. Cycle threshold (CT) values from the Roche systmwere used as measures of relative quantification. Results: A total of 1065 HIV-exposed infants (median age, 47 days) undergoing SOC testing with final infant status available were included in the study. The first Alere q test resulted in an error for 60 samples (6%) but 70% of all errors were resolved with a second Alere q test. The performance of Alere q is shown in Table 1. Excluding errors, overall specificity was 100% (lower bound of 95% confidence interval [CI], 99.5%) and sensitivity was 96.8% (95% CI, 93.2%-98.8%). False negative samples had a median CT value of 32.8 on the SOC assay, higher than both the true positives (median CT, 24.2; p<0.001) and errors (median CT, 21.0; p<0.001). When analysis was restricted to specimens from newborns tested at <3 days of age, specificity remained high (100%) but sensitivity decreased to 91.6%.

Table 1. Performance of Alere q point-of-care test compared to Roche CAP/CTM HIV-1 qualitative PCR for early infant diagnosis, based on 1065 children with final infant HIV status available. Conclusions: These results demonstrate good performance characteristics of this POC assay used for EID in the laboratory setting. While POC testing for EID may have particular utility in the context of birth testing within delivery facilities, the lower sensitivity of tests conducted within 3 days of birth require attention. Higher CT values were observed for false negative results, possibly due to lower levels of circulating virus during early infection. Further research is required to determine whether similar results can be achieved when this technology is implemented in clinical care settings, including for in birth testing. 35 Early ART and Sustained Virological Suppression Limits HIV Proviral DNA Reservoir: CHER Evidence Helen A. Payne 1 ; SarahWatters 1 ; Marvin Hsaio 2 ; Robin Callard 1 ; Abdel Babiker 3 ; Mark F. Cotton 4 ; Kennedy Otwombe 5 ; AvyViolari 5 ; Diana M. Gibb 3 ; Nigel J. Klein 1 1 University College London, London, United Kingdom; 2 University of Cape Town, Cape Town, South Africa; 3 MRC Clinical Trials Unit at University College London, London, United Kingdom; 4 Stellenbosch University, Cape Town, South Africa; 5 University of Witswatersrand, Johannesburg, South Africa Background: Improved understanding of HIV-1 proviral DNA latent reservoir formation and impact of ART-strategies on reservoir size can inform treatment strategies in paediatric HIV. Methods: HIV-1 proviral DNA was measured from a substudy of 118 children from the Children with HIV Early Antiretroviral Therapy (CHER) trial where HIV-infected infants <12 weeks with CD4% ≥ 25%were randomised to early limited ART for 40 or 96 weeks or deferred ART. For Infants on deferred ART or following ART interruption after 40/96 weeks ART was started/re-started for clinical progression (CDC severe stage B/C disease) or CD4%<20%. HIV-1 proviral DNA was measured by quantitative PCR using DNA extracted from 384 cryopreserved PBMC samples taken 12-weekly from 40 to 252 weeks after a minimum of 24 weeks of ART. The effects on proviral DNA decline of early versus deferred ART and ART- interruption were investigated. Predictive factors for reservoir decline were explored including ART duration, enrolment CD4 and CD4 at 96 weeks, HIV serostatus and quantitative HIV-antibody at 84 weeks, baseline CMV viraemia, immunological phenotypes, enrolment viral load, viral load 9-12 months prior to proviral DNA measurement and total weeks continuous suppression below 400 copies/ml. The profiles of 5 children with undetectable proviral DNA measurements were also described. Results: After a minimum 24 weeks of ART, 73 children starting early ART showed a trend towards less HIV-1 proviral DNA compared with 45 children on deferred ART: median 27 [IQR 8 – 51] versus 100 [48 – 202] copies of provirus per 10 5 PBMCs, p=0.08). Overall, reduced reservoir size and probability of developing an undetectable reservoir were strongly associated with earlier ART-initiation and longer continuous virological suppression (p-values all <0.0001). However patterns of decline varied despite continuous ART and apparent virological suppression. ART-interruption only modestly increased levels of proviral DNA (p=0.03). HIV serostatus did not correlate with reservoir size (p=0.92) but higher CMV DNA levels at enrolment were associated with an increased HIV reservoir (p=0.02). Four children with undetectable proviral DNA underwent ART-interruption as per CHER randomisation and exhibited HIV-1 viral resurgence. Conclusions: These findings inform the interplay between clinical, immunological or virological factors involved in reservoir dynamics, and support the view that early-initiation of ART and sustained virological suppression are key to reservoir reduction. 36 Long-Term Outcomes of HIV-Infected Children Initiating NVP vs LPV/r-Based Treatment Linda Barlow-Mosha 1 ; Konstantia Angelidou 2 ; Moherndran Archary 8 ; AvyViolari 7 ; Jane Lindsey 2 ; Lynne Mofenson 3 ; Patrick Jean-Philipe 5 ; Paul E Palumbo 4 ; Benjamin Chi 6 On behalf of the IMPAACT P1060 ProtocolTeam 1 Makerere University–Johns Hopkins University Research Collaboration, Kampala, Uganda; 2 Harvard School of Public Health, Center for Biostatistics in AIDS Research, Boston, MA, US; 3 National Institutes of Health, Bethesda, MD, US; 4 Geisel School of Medicine at Dartmouth, Lebanon, NH, US; 5 Henry M. Jackson Foundation for the Advancement of Military Medicine, Rockville, MD, US; 6 University of North Carolina at Chapel Hill, Chapel Hill, NC, US; 7 University of Witswatersrand, Johannesburg, South Africa; 8 University of KwaZulu-Natal, Durban, South Africa; 9 IMPAACT, SilverSpring, MD, US Background: IMPAACT P1060 demonstrated short-term superiority of lopinavir/ritonavir (LPV/r)-based ART over nevirapine (NVP) for the primary endpoint (stopping randomized treatment, virologic failure [VF] or death by 24 weeks) in HIV-infected children regardless of NVP exposure at birth. In contrast, those on NVP had marginally superior improvements in CD4% and growth (weight and height z-scores). Longer-term outcomes are presented. Methods: HIV-infected ART-eligible infants and children (2m - 3y) from 6 African countries and India enrolled into 2 cohorts based on prior NVP exposure (PrNVP) and were randomized to initiate NVP or LPV/r (with zidovudine and lamivudine). The study DSMB recommended closing enrollment and unblinding cohorts with PrNVP (2009) and no PrNVP (2010) due to superiority of the LPV/r arm for the primary endpoint. Participants could switch regimens and continue in observational follow-up. Randomized and observational data were combined in intent-to-treat (ITT) analyses to investigate long-term trends in VF and death (Cox proportional hazards models) and CD4% and growth (generalized

Oral Abstracts

95

CROI 2015