CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

stored for up to 14 days at -20oC, room temperature (RT) and +37oC. To evaluate sensitivity, DBS from 500 HIV infected subjects were tested and compared to matched plasma. Reproducibility of the DBS results with low plasma signal to cutoff ratio (S/CO) levels was evaluated by testing 12 samples in replicates. Results: DBS results were reproducible in both 12mm (CV 1-8.3%) and 6-mm (CV 1.9-5.8%). S/CO from 12mm DBS were up to 2 fold higher compared to 6mm. DBS remained HIV reactive after 14 days storage. We observed <7% drop in S/CO at -20oC, <12% at RT and ≤20% at +37oC on day 14. Of 500 DBS samples with HIV Ag/Ab reactive matched plasma, 471 (94.2%) were reactive and 29 (5.8%) nonreactive. All samples with a plasma S/CO>23 (n=465) were reactive by DBS. Of the 35 samples with S/CO<23 only 6 (17%) DBS were reactive. DBS replicates for samples with 7-30 S/CO in plasma were concordant for 11 samples and discordant for only one sample. For 2 samples with 7-10 S/CO in plasma all replicates were nonreactive (n=40, CV 24.7%). Of 9 samples with 11-23 S/CO in plasma, 4 were reactive in all replicates (n=76, CV 2.52-19.97%) and 5 were nonreactive in 78 of 80 (97.5%) replicates (CV 4.99-172.6%); one sample with plasma S/CO>23 was reactive in all replicates (n=20, CV 4.44%).The detection rate for samples with plasma S/CO range of 7-10, 11-23 and >23 was estimated as 0%, 52% and 100% respectively. Conclusion: The results indicate that Whatman 903 DBS is a suitable specimen type for the ARCHITECT HIV Ag/Ab Combo assay. The assay reliably detects HIV-1 p24 antigen/ anti-HIV-1/-2 antibodies in DBS with corresponding plasma S/CO>23. According to the Abbott Global Surveillance Database where samples were collected all over the world and characterized over 15 years, 95.4% of HIV-infected specimens have HIV Ag/Ab results of S/CO>23 in plasma or serum. 511 RECENCY STAGING OF HIV INFECTIONS THROUGH ROUTINE DIAGNOSTIC TESTING Eduard Grebe 1 , Alex Welte 1 , Jake Hall 2 , Michael P. Busch 3 , Shelley Facente 4 , Sheila Keating 2 , Kara Marson 4 , Christopher D. Pilcher 4 , Gary Murphy 2 , for the CEPHIA 1 Stellenbosch Univ, Stellenbosch, South Africa, 2 Pub Hlth England, London, UK, 3 Blood Systems Rsr Inst, San Francisco, CA, USA, 4 Univ of California San Francisco, San Francisco, USA Background: Assay based staging of HIV for recency of infection has multiple purposes: at the population level, it enables cross-sectional incidence estimation. At the individual level, at diagnosis (as available in some national programmes and being contemplated in other large scale systems) recent/non-recent infection classification helps guide psychosocial support strategies, contact tracing, or inclusion in clinical trials. However, as recency testing is currently a specialist service using custom incidence assays, there is additional expense, and a delay between HIV diagnosis and the delivery of the recency result. Given the high dynamic range inherent in widely used (primarily chemiluminescent) diagnostic platforms, we explore whether this unutilized information (signal/cutoff ratio, S/CO) can immediately stage new diagnoses as recent/non-recent, or at least identify specimens that need not be referred for specialised recency testing, allowing prioritisation of specimens. Methods: 2500 specimens with good clinical characterisation were tested diagnostically on the Abbott Architect 4th generation assay and by Sedia Limiting Antigen Assay for recency determination. We compared the recency classifications based on the two platforms through a number of regressions and correlations, and estimated mean duration of recent infection (MDRI) for a number of thresholds on Architect S/CO values. Results: At Architect S/CO < 150, MDRI was 163 days, and ART naïve False Recent Rate (FRR) was 2.7%, comparable with previously published LAg values. Individual Architect/ LAg results were highly correlated (r=0.81). Figure 1 shows the probability of specimens classifying as LAg recent (ODn<1.5) as a function of ARCHITECT S/CO: more than 80% of specimens with S/CO<100, less than 5%with S/CO>400, and less than 1% of specimens with S/CO>500 scored recent by LAg (ODn<1.5). Conclusion: An unmodified chemiluminent HIV immunoassay assay can provide comparable information to a custom recency staging assay. In the context of population HIV incidence surveillance, this can lead to simple, readily transferable and cheaper testing protocols. At patient diagnosis, this could enirely eliminate the costs and delays associated with additional recency testing, or at least enable selection of a subset of specimens (high- or low- enough reactivity) for which final staging assignments do not require additional testing. 512 DEVELOPMENT OF A HIGH-THROUGHPUT MULTIPLEX ASSAY FOR MEASURING HIV INCIDENCE Martin Stengelin 1 , Daisy Roy 1 , Sudeep Kumar 1 , Kara Marson 2 , Steven G. Deeks 2 , Gary Murphy 3 , Michael P. Busch 4 , Christopher D. Pilcher 2 1 Meso Scale Diagnostics, LLC, Rockville, MD, USA, 2 Univ of California San Francisco, San Francisco, CA, USA, 3 Pub Hlth England, London, UK, 4 Blood Systems Rsr Inst, San Francisco, CA, USA Background: In order to assess the impact of HIV prevention strategies, it is critical to measure the rate at which new HIV infections are occurring in populations. To achieve needed performance requirements (e.g., long “mean duration of recent infection” [MDRI], low “false recent rate” [FRR]), most programs currently use multi-assay algorithms including avidity-modified antibody and viral load measurements. MULTI-ARRAY® is a high throughput technology with a wide dynamic range and low non-specific binding that has been used successfully in a variety of applications. We determined feasibility of an improved multiplex HIV incidence assay to discriminate recent from longstanding HIV infection using the MULTI-ARRAY platform. Methods: Using MULTI-ARRAY technology, we measured antibody quantity and avidity to ten HIV proteins. A total of 28 assays were run: standard serology assays with and without disrupting agent, and an assay format with anti-human IgG capture and detection with SULFO-TAG™ labeled HIV antigens. 96 samples were tested: 75 samples from the CEPHIA Developmental set (http://www.incidence-estimation.com/cephiaqueries/cephiaDB/overview), 15 samples from the SeraCare Incidence/Prevalence Performance Panel, and additional samples from apparently healthy individuals. Results: Several assays could discriminate recent from longstanding HIV infection even as stand-alone markers if samples from Elite Controllers were excluded: the standard serology format with and without pretreatment for gp120 and gp160, and the antibody capture format for gp120 showed 100% sensitivity and 100% specificity in this sample set. In a ROC analysis, 13 assays had ROC areas of 0.90 or better (elite controllers excluded). None of the tested antibody assays was able to discriminate elite controllers; thus including a (antigen or nucleic acid) viral load assay would be required. The time dependence of the gp120 and gp160 ECL signal as function of time from seroconversion indicates that the signal continues to increase even after two years, indicating that determining an MDRI of well over a year at a low FRR is feasible. Conclusion: Assays to discriminate recent from longstanding HIV infection have been developed in a 96-well high-throughput assay format for the MESO® SECTOR S 600 Imager and the MESO QuickPlex® SQ 120. 513 IDENTIFYING RECENT HIV INFECTIONS: AN INDIVIDUALIZED ASSESSMENT OF RISK Jaythoon Hassan 1 , Joanne Moran 1 , Kate O’Donnell 2 , Gary Murphy 3 , Derval Igoe 2 , Cillian De Gascun 1 , for the Monitoring Recently Acquired HIV Infection Group 1 Univ Coll Dublin, Dublin, Ireland, 2 Hlth Protection Surveillance Cntr, Dublin, Ireland, 3 Pub Hlth England, London, UK Background: The accurate identification of recent HIV infection remains an important area of research to inform population-based HIV prevention and treatment intervention policies. Methods that use cross-sectional testing and biomarker information might be an alternative to longitudinal testing, as combinations of serological and molecular methods can potentially provide a means to identify recent HIV infections. The aim of this study was to develop a predictive scoring systemwhich was based on combining the results of Schupbach’s Line assay algorithm 15.1 and the viral load (VL) to predict the risk of having recently acquired HIV infection. Methods: New HIV diagnoses in Ireland from January to April 2016 (n=151) were included in the study. All samples were tested on the Sedia limiting antigen avidity assay (LAg). The normalised cut-off in the LAg assay is 1.5. Schupbach’s (2015) Algorithm 15.1 was applied to the Line assay results. This algorithm is derived from antibody reaction scores to HIV antigen bands on the LIA strip. Patients on antiretroviral treatment or previously diagnosed (>12 months) were excluded from the analysis (n=43). The Speigelhalter-Knill- Jones method was used to develop a predictive scoring systemwhich is based on the LAg assay as a gold standard as this assay demonstrated 100% accuracy in identifying recency based on samples tested from the CEPHIA repository. Viral loads above the median of the cohort were used as an indicator of recency. Results: Patient demographics showed that the recent cohort was predominantly male (87.1%) and MSM/bisexual (78.9%). The LAg assay and LIA Algorithm 15.1 identified 32 cases (21.2%) and 19 cases (12.6%) respectively as recently acquired HIV. The median viral load of the cohort was 16,428 copies/ml (log4.2). The results of the regression model including both the LIA and the HIV VL to predict recency are shown in Table 1. Combining both Algorithm 15.1 and VL demonstrated that the observed risk in our cohort of being recent is 100%. Using standard laboratory assays, this predictive scoring system allows an individualised assessment of risk for prediction of recency.

Poster and Themed Discussion Abstracts

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