CROI 2016 Abstract eBook

Abstract Listing

Poster Abstracts

499 Genome-Wide Association of HIVWhole Genomes Provides Insights Into Drug Resistance Robert A. Power 1 ; Siva Davaniah 1 ; Anne Derache 2 ; EduanWilkinson 1 ; FrankTanser 2 ; Ravindra K. Gupta 3 ; Deenan Pillay 2 ;Tulio de Oliveira 4 1 Wellcome Trust Africa Cntr for Hlth and Pop Studies, Somkhele, South Africa; 2 Africa Cntr for Hlth and Pop Studies, Mtubatuba, South Africa; 3 Univ Coll London, London, UK; 4 Univ of KwaZulu- Natal, Durban, South Africa Background: Genome-wide association studies (GWAS) have considerably advanced our understanding of human traits and diseases. With the increasing availability of whole genome sequences (WGS) for pathogens, it is important to establish whether GWAS of viral genomes could reveal important biological insights. Here we perform the first proof of concept analysis examining the selection of antiretroviral therapy (ART) associated variants. Methods: We performed a GWAS of drug resistance (DR) in a sample of 343 HIV subtype C patients failing 1 st line treatment in rural KwaZulu-Natal, South Africa. The majority and minority variants within each sequence were called using GATK and PILON, and GWAS was performed within PLINK. HIV WGS from patients exposed to different antiretroviral drugs (zidovudine, stavudine, tenofovir, efavirenz, nevirapine and lopinavir) were compared to sequences derived from individuals naïve to the respective treatment. Results: GWAS methodology was validated by identifying five associations on a genetic level that led to amino acid changes known to cause DR. Further, we identified two variants within amino acid 68 of the reverse transcriptase protein associated with tenofovir exposure (p-value=5.38E-06 & 1.45E-05; Odds Ratio=11.9 & 2.89) previously described as potential fitness compensatory mutations. We replicated these associations in the Stanford University HIV Drug Resistance Database (488 exposed vs. 9,357 unexposed, p<0.001). We also identified a possible additional DR variant for tenofovir within amino acid 91 of the matrix region of the Gag protein. Replication in publicly available datasets was not possible here due to the lack of Gag sequences. Conclusions: These results validate the applicability of GWAS to HIV WGS data with respect to phenotypes with large genetic effects such as DR. The sample size required was also relatively small. The data also highlight how GWAS can provide novel and possibly clinically relevant insights into pathogen genomes in an era of high throughput sequencing. 500 Receipt and Timing of Genotypic HIV Drug Resistance Testing in the United States Sharoda Dasgupta1; H. Irene Ha ll 1 ; Angela L. Hernandez 1 ; M. Cheryl Banez Ocfemia 1 ; Neeraja Saduvala 2 ; Alexandra M. Oster 1 1 CDC, Atlanta, GA, USA; 2 ICF Intl, Atlanta, GA, USA Background: The U.S. Department of Health and Human Services recommends genotypic HIV drug resistance (DR) testing upon entry to care; however, receipt and timing of DR testing has not been well characterized. We examined DR testing at and after initiation of HIV care in the United States. Methods: We analyzed data from the U.S. National HIV Surveillance System (NHSS) for persons aged > 13 years with HIV infection diagnosed in 2013 who were linked to care (i.e., had a CD4 count or viral load test) within 3 months of diagnosis and resided in a jurisdiction with complete laboratory reporting and high reporting of nucleotide sequence data from DR testing (Los Angeles County, Michigan, New York, South Carolina, Texas, and Washington). We assessed the proportion of individuals who received DR testing at or after linkage and the distribution of time between linkage to care and DR testing. Among those who received DR testing, we conducted Mantel-Haenszel chi-square tests to identify factors associated with testing at the same time (i.e., in the same month) as linkage to care. Results: Of 11,351 persons in these jurisdictions who received a diagnosis of HIV infection during 2013, 9,435 (83%) were linked to care within 3 months of diagnosis. Among those linked to care, 6,106 (65%) ever received DR testing and 5,996 (64%) received DR testing within 12 months of linkage to care. Of those tested within 12 months of linkage, 4,195 (70%) received DR testing in the same month as linkage and an additional 1,153 (19%) within 1 month of linkage. The proportion of individuals who received testing at the time of linkage differed significantly across racial/ethnic groups (p = .01) and age groups (p = 0.03). The proportion receiving DR testing at linkage was lower among blacks/African Americans (66%) compared to whites (71%) and Hispanics/Latinos (70%), and among those aged < 35 years (67%) compared to older individuals (70-71%). Conclusions: NHSS data indicate that almost two-thirds of HIV-infected persons linked to HIV care received DR testing within 12 months of initiation of care, which may be an underestimate if not all DR tests were reported to surveillance. The timing of DR testing suggests that most providers order DR testing at entry to care as recommended. 501 HIV Integrase Genotypic Resistance Testing Among HIV-Infected Persons in New York ZhengyanWang 1 ; Daniel Gordon 1 ; EmilyWalits 2 ; Joanne Gerber 1 ; Deepa Rajulu 1 ; Lou Smith 1 ; Bridget Anderson 1 1 New York State Dept of Hlth, Albany, NY, USA; 2 Univ of Albany Sch of PH, Albany, NY, USA Background: Data on integrase (IN) inhibitor resistance come mainly from clinical trials and in vitro studies and there are few population-based IN resistance studies. Since IN inhibitors-based regimens are now commonly recommended as initial regimens but routine screening for IN resistance is not recommended, it is important to monitor population- based information on IN resistance among the newly diagnosed HIV patients. Methods: Laboratories conducting genotypic resistance testing for residents of New York State (NYS) are required to report the nucleic acids sequences to NYS Department of Health (DOH). HIV integrase genotypic resistance tests (IN-GRTs) received 12/09 through 7/15 were paired with cases’ PR-RT tests for the same date. Sequences were analyzed by NYSDOH’s in-house Resistance Analysis System. The first IN test result for each individual was linked to case in NYS’ HIV surveillance registry. IN tests within 3 months of HIV diagnosis were classified as “initial”. Time from diagnosis to IN test, case demographics, IN resistance, and the relation of IN and PR-RT resistance were examined.

Poster Abstracts


CROI 2016

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