CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

homozygous and HLA-C1 allele homozygous) was identified as a significant viral load predictor ( β =0.13, p=0.039 by linear regression model). 4) In longitudinal analysis, higher mortality rate was identified among the subjects with higher number of HLA-C1-KIR2DL3 associations (p=0.002 by log rank test; aHR=2.0, 95% CI 1.3-3.2, p=0.004 by Cox hazard model) (Figure). 5) However, no advantage of HLA-Bw4-KIR3DL1/S1 on clinical outcome was found in this cohort.

Figure. The number of KIR2DL3-ligand HLA associations and survival rate analysis, log rank test. Conclusions: In this study, the effects of HLA-C and KIR2D interaction with a focus on the effect of the detrimental HLA-C1-KIR2DL3 association, on clinical outcome among HIV-1 CRF01_AE-infected Thais were investigated. These findings will impact the existence of the unique anti-HIV innate immune pressure and viral adaptation to such pressure in each endemic area. 276 HLA-KIR-Associated Sites in Gag and Their Effects on Clinical Outcome in Thailand Masahiko Mori 1 ; NuanjunWichukchinda 2 ; Reiko Miyahara 1 ; Archawin Rojanawiwat 2 ; Panita Pathipvanich 3 ;Toshiyuki Miura 1 ; MichioYasunami 1 ; Koya Ariyoshi 1 ; Pathom Sawanpanyalert 2 1 Institute of Tropical Medicine, Nagasaki University, Nagasaki City, Japan; 2 Ministry of Public Health, Nonthaburi, Thailand; 3 Day Care Centre, Lampang Hospital, Lampang, Thailand Background: Viral peptides (epitope) are presented by class I HLA molecules to both cytotoxic T lymphocyte (CTL) through T cell receptor (TCR), and natural killer (NK) cell through killer immunoglobulin-like receptor (KIR). Compared to the studies about anti-HIV immune pressure by CTL and its related viral adaptation, studies about NK cell remain sparse. Methods: 208 HIV-1 CRF01_AE-infected treatment naïve Thais were recruited. Their clade I HLA allele, KIR, viral load, and Gag sequence data were collected, and 1) HLA-KIR- associated Gag mutation or preservation sites by Fisher’s exact test with 95% confidential interval, 2) effects of HLA-KIR-associated sites on viral load by Mann-Whitney U-test, 3) correlation between the number of associated sites and viral load by Spearman’s correlation test, and 4) the number of associated sites and survival rate by log rank test and Cox hazard model, were analyzed. Results: 1) 52 HLA-KIR-associated sites (20 sites at p17, 15 sites at p24, and 17 sites at p15) were identified, 2) 6 out of 52 sites also scored viral load difference between association positives and negatives with significance; 4 out of 6 sites scored lower viral load among associated mutation positives, suggesting viral escape mutations with lower viral set point by HLA-KIR-derived immune pressure. 3) Negative correlation between the number of mutation at above 4 protective sites and viral load was identified (r=-0.18, p=0.0023). Among 4 sites, 3 sites were HLA-Bw4-KIR3DL1-associated mutations (I104X, N252X, and T454X). Finally in longitudinal analysis, 4) Among HLA-Bw4-KIR3DL1 positives, higher number of HLA-Bw4-KIR3DL1-associated mutations also scored higher survival rate (p=0.0088 by log rank test (Figure), and 0.63 (0.47-0.84) of hazard ratio (95% CI), p=0.002 by Cox hazard model).

Poster Abstracts

Figure. The number of HLA-Bw4-KIR3DL1-associated sites and survival rate analysis, by log rank test. Survival rate difference among the groups of HLA-Bw4-KIR3DL1- associated sites number (from 0 to 3) are shown. All n=136 subjects are HLA-Bw4+KIR3DL1+. Conclusions: KIR-HLA-associated sites in Gag were identified, and several sites were strongly associated with clinical outcomes by cross sectional and longitudinal analysis. These findings imply the existence of immune pressure by NK cell and consequent viral adaptation. These findings will contribute to further development of epitope-based vaccine study. 277 In KIR3DL1/S1 Heterozygotes Are KIR3DL1 and KIR3DS1 Co-Dominantly Expressed? Zahra Kiani 1 ; Nicole F. Bernard 1 ; Julie Bruneau 2 1 McGill University, Montreal, Canada; 2 Centre de Recherche du Centre Hospitalier de l’Universite de Montreal, Montreal, Canada Background: Epidemiological studies show that co-carriage of KIR3DS1 ( 3DS1 ) and a subset of HLA-Bw4 alleles with an isoleucine at position 80 of the HLA heavy chain ( 3DS1+*80I ) is associated with slow time to AIDS. NK cells from 3DS1+*80I carriers have high anti-HIV activity. There is conflicting information regarding whether NK cells from KIR3DL1/S1 heterozygotes (htz) exhibit allelic exclusion or co-dominance in terms of expression of the NK cell receptors 3DS1 and KIR3DL1 (3DL1). Monoclonal antibody (mAb) Z27

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CROI 2015