CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

Kaplan-Meier analysis revealed a significant, early and durable impact of point of care CD4 testing compared to referral lab CD4 testing, on proportion linked to care after home- based HIV testing. Conclusions: Final results of the first RCT on the impact of POC CD4 testing in a resource-limited HBCT setting revealed significant improvements in rate of LTC and ART initiation. Further analyses on time to ART initiation, and predictors of LTC and ART initiation, are ongoing. 633 Reliable Genotypic Tropism Tests for the Major HIV-1 Subtypes Kieran Cashin 1 ; Lachlan R. Gray 1 ; Katherine L. Harvey 1 ; Danielle Perez-Bercoff 2 ; Guinevere Q. Lee 3 ; Jasminka Sterjovski 1 ; James F. Demarest 4 ; Fraser Drummond 4 ; Melissa J. Churchill 1 ; Paul R. Gorry 1 1 Burnet Institute, Melbourne, Australia; 2 Centre Recherche Public de la Santé, Strassen, Luxembourg; 3 BC Centre for Excellence in HIV/AIDS, Vancouver, Canada; 4 ViiV Healthcare, Durham, NC, US Background: The major obstacles to the CCR5-antagonist maraviroc being more widely used in anti-HIV-1 therapy regimens are (i) traditional pre-treatment phenotypic tropism tests to determine virus susceptibility to maraviroc are expensive and time consuming, and (ii) cheaper and more rapid genotypic tropism tests have been developed primarily for HIV-1 subtype B strains, which account for only 10% of infections worldwide. We therefore developed PhenoSeq, a suite of reliable genotypic tropism tests specific for HIV-1 subtypes A, B, C, D and circulating recombinant forms of subtypes AE (CRF01_AE) and AG (CRF02_AG), which together account for 95% of infections worldwide. Methods: Development of subtype-specific genotypic tropism tests was informed by analysis of all HIV-1 env third variable region (V3) amino acid sequences from the Los Alamos HIV Database that had corresponding phenotypic tropism and HIV-1 subtype data (n=2257; 630 CXCR4-using and 1637 CCR5-using), to elucidate statistically significant sequence alterations that distinguish CXCR4- from CCR5-using viruses. With the aid of a new bioinformatic tool that we developed (bulk2clonal), PhenoSeq algorithms were validated against independent clinical HIV-1 sequence panels from patients previously enrolled in the Pfizer trials A4001064 and MERIT, relative to results of the original Trofile assay (OTA) and the enhanced sensitivity Trofile assay (ESTA). Results: Our analyses show that the PhenoSeq genotypic algorithms exhibit more favourable sensitivity and specificity profiles for establishing the tropism of HIV-1 subtypes A, B, C, D, CRF01_AE and CRF02_AG than current alternative algorithms, including the clinically validated in-use algorithms geno2pheno (g2p; false positive rate 5.75% and 10%) and WebPSSM (Table 1). Furthermore, PhenoSeq area under the receiver operator characteristic curves (AUROC) were significantly greater than g2p FPR 5.75% for establishing the tropism of HIV-1 subtype C (p=0.01), g2p FPR 10% for CRF01_AE (p=0.03), and WebPSSM for subtypes B (p=0.01) and D (p=0.05) (two-tailed t-test, p ≤ 0.05 considered significant). Performance of genotypic tropism tests against independent V3 sequences

Poster Abstracts

Sens, % sensitivity was calculated by dividing the number of correctly predicted CXCR4-using sequences by the total number CXCR4-using sequences and multiplying by 100. Spec, % specificity was calculated by dividing the number of correctly predicted R5 sequences by the total number of R5 sequences and multiplying by 100. P-values (two-tailed) for comparisons of area under the receiver operator characteristic curve (AUROC) <0.05 were considered significant and are highlighted in bold text. g2p, geno2pheno. OTA, original Trofile assay. ESTA, enhanced sensitivity Trofile assay. LANL, Los Alamos HIV Database. FPR, false positive rate. *The subtype C specific WebPSSMSI/NSI algorithm was used for subtype C HIV-1 predictions.

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CROI 2015