CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

amplicons analyzed: gp41=128415, pol=74452; Figure) suggesting that the donor virus, if present, was not reactivated in spite of temporary withdrawal of ART. Conclusion: This study monitoring recipient HIV sequences for up to two years post-transplant reveals no evidence of sustained donor-derived HIV-SI, even in one recipient following temporary ART non-adherence. These findings suggest that HIV-SI may not be a significant clinical concern in well-monitored ART suppressed recipients. Nevertheless, further monitoring of viral populations in a larger cohort of HIV+ transplant recipients is needed to investigate and fully assess the clinical and virologic significance of donor-derived HIV-SI.

detected 369 days later (env subtype F2, pol subtype C); both strains were present at the follow-up visit. In the other two cases, the viral strain present at seroconversion shifted entirely to a new strain. In one case, the subtype C strain present at seroconversion was replaced with an inter-subtype recombinant strain 181 days later (env subtype A1, pol subtype C). In the other case, the subtype C strain present at seroconversion was replaced with a different subtype C strain 184 days later. Conclusion: This study revealed a high incidence of SI in a cohort of MSM and TGW from sub-Saharan Africa. The incidence of SI was higher than the incidence of primary infection, and involved new infection with inter-subtype recombinant HIV strains in two of three cases. Brad Sherman 1 , Xiaojun Hu 1 , Kanal Singh 2 , Lillian Haine 3 , James Neaton 3 , Jens D. Lundgren 4 , H. Clifford Lane 2 , for the INSIGHT Study Group 1 Frederick National Laboratory for Cancer Research, Frederick, MD, USA, 2 NIAID, Bethesda, MD, USA, 3 University of Minnesota, Minneapolis, MN, USA, 4 Rigshospitalet, Copenhagen, Denmark Background: Elevations in IL-6, D-dimer, and hsCRP, are associated with increased incidence of comorbid disease & mortality among HIV+ individuals (PLWH). Prior studies suggest a genetic basis for these biomarker elevations among certain ethnicities. We performed a genome-wide associated study (GWAS) using 3 HIV+ cohorts to identify single nucleotide polymorphisms (SNPs) associated with elevations in these 3 biomarkers in PLWH. Methods: 7,192 participants across 3 established multi-ethnic HIV+ cohorts (START, SMART, ESPRIT) were studied. Baseline levels of hsCRP, D-dimer and IL-6 were measured & SNPs identified using a custom Affymetrix Axiom SNP array with 770,558 probes. Five ancestral ethnic groups were assigned (African, American, European, South and East Asian). Principal component (PC) analysis was used to account for population stratification, and single variant analysis was performed for each biomarker using multiple linear regression models incorporating the first 10 PCs, gender, age, CD4 count, HIV viral load, BMI, smoking (missing in ESPRIT) and biomarker related traits (CVD, diabetes, Hepatitis B & C) at baseline as covariates for combined and ethnicity-specific cohort samples. To increase power, a fixed-effects meta-analysis was conducted with inverse variance weighting for all samples, and those from the 3 largest ethnic ancestry groups (African, n=1732, American, n=645, European, n=4675). Results: Allele frequencies varied by genotyped ethnicity, but associations between each biomarker and allele frequency did not, therefore results from the cross-cohort meta-analyses are cited. 22 SNPs within 3 gene loci (CRP, HNF1A and APOE) reached genome-wide significance (GWS, P < 5 x 10-8) for hsCRP; 3 SNPs within 2 gene loci (coagulation factors F3 and F5) reached GWS for D-dimer; and 27 SNPS within 1 locus (IL6R) reached GWS for IL-6. (Fig.a,b,c). These loci have been previously described in non-HIV populations, mostly from studies of individuals of European descent. Conclusion: Multiple SNPs were associated with elevations in hsCRP, D-dimer, and IL-6 in HIV+ individuals from 3 ethnically diverse cohorts. These findings support the hypothesis that host genetics partially contribute to chronic inflammation in this population and identify potential targets for intervention.

195 GENETIC DETERMINANTS OF hsCRP, D-DIMER, AND IL-6 IN 3 MULTIETHNIC HIV COHORTS

Poster Abstracts

194 HIV SUPERINFECTION AMONG MSM AND TGW IN SUB-SAHARAN AFRICA: HPTN 075 Philip J. Palumbo 1 , Yinfeng Zhang 1 , Mariya V. Sivay 1 , Xu Guo 2 , Vanessa Cummings 1 , Erica Hamilton 3 , Wairimu Chege 4 , Arthur Ogendo 5 , Noel Kayange 6 , Ravindre Panchia 7 , Karen Dominguez 8 , Ying Qing Chen 2 , Theodorus Sandfort 9 , Susan H. Eshleman 1 , for the HPTN 075 Study Team 1 Johns Hopkins University School of Medicine, Baltimore, MD, USA, 2 Fred Hutchinson Cancer Research Center, Seattle, WA, USA, 3 FHI 360, Durham, NC, USA, 4 DAIDS, NIAID, Bethesda, MD, USA, 5 KEMRI–Centre for Global Health Research, Kisumu, Kenya, 6 Malawi College of Medicine-Johns Hopkins University Research Project, Blantyre, Malawi, 7 University of the Witwatersrand, Soweto, South Africa, 8 University of Cape Town, Cape Town, South Africa, 9 Columbia University, New York, NY, USA Background: HIV superinfection (SI) occurs when an infected person is infected with a new, distinct HIV strain. High rates of HIV SI have been reported among men who have sex with men (MSM). The HIV Prevention Trials Network (HPTN) 075 study evaluated the feasibility of recruiting and retaining MSM in sub-Saharan Africa in HIV clinical trials. We used next-generation sequencing (NGS) to assess SI among MSM and transgender women (TGW) enrolled in the HPTN 075 study. Methods: HPTN 075 participants had quarterly visits with up to 12 months follow-up. The HPTN 075 study included 72 participants who were HIV-infected at enrollment (ENR+); 28 had a 12-month sample with a viral load >400 copies/ mL. Twenty-one of 329 acquired HIV during the study (seroconverters); 17 (52.4%) had a sample from>30 days after the first HIV-positive visit (range: 38-316 days). HIV RNA was extracted using the ViroSeq HIV-1 Genotyping System. NGS was performed using the MiSeq System (env and pol regions). Phylogenetic analysis was used to identify and characterize SI events. Results: Sequencing results were obtained for 27/28 ENR+ participants (one failed analysis) and for 11/17 seroconverters (6 failed analysis). Three cases of SI were identified; these included one (3.7%) of 27 ENR+ participants and two (18.2%) of 11 seroconverters. The incidence of SI among seroconverters (30.3/100 person-years [py]) was higher than among ENR+ participants (3.6/100 py; p=0.08) and was significantly higher than the rate of primary HIV infection in the HPTN 075 cohort (6.96/100 py; p=0.046). In one case, subtype C was present at enrollment and an inter-subtype recombinant strain was

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CROI 2020