Oral Abstract Session 01 - Global HIV Vaccine Enterprise

Topic 6: Immunogenetic Factors
P06.05
Human Leukocyte Antigen Class I Supertypes and
Viral Control in HIV-1 Infected Former Plasma Donors
from China
J. Hao 1 , K. Hong 1 , J. Chen 1 , M. Jia 1 , Y. Ruan 1 , Y. Shao 1
1National Center for AIDS/STD Control and Prevention, Beijing,
China
Background: The role of human leukocyte antigen (HLA) class I
supertypes in controlling human immunodeficiency virus type 1
(HIV-1) infection in Chinese has not been established. The aim
of this study is to examine the frequency of HLA-A and HLA-B
alleles and supertypes of 222 HIV-1 infected former plasma
donors in central China and to investigate their impact on HIV-1
viral control.
Methods: HLA-A and HLA-B alleles were genotyped with PCR-SSP
and sequence-based typing assay to four-digit resolution. The
HLA alleles were classified functionally to 4 HLA-A supertypes
and 6 HLA-B supertypes according to their shared peptide
binding properties. Plasma viral load was determined using the
Roche Amplicor ultrasensitive assay which has a lower detection
limit of 50 copies HIV-1 RNA per ml.
Results: HLA-A03 supertypes(A03s) and HLA-B62 supertypes(B62s)
were associated with lower viral load (P=0.0206, P=0.0483),
whereas HLA- A24 supertypes(A24s) appeared to have an
association with higher viral load (P=0.0483). There was a highly
significant correlation between the genotypic supertypes(GS)
and viral load (Kendall’s tau b = 0.180, P=0.000). The median viral
load was lower among A*3001(P=0.0139)、A*1101(P=0.0096)
、B*5101(P=0.0025)、B*3501(P=0.0091) or B*4601(P=0.001)
carriers and higher in A*2301(P=0.0106) carriers.
Conclusion: HLA-A03s and -B62s may be associated with
favorable HIV-1 viral control, A24s associated with unfavorable
viral control; HLA-B*4601 within B62s and HLA-A*2301 within
A24s might contribute to the outcomes of HIV-1 viral control.
P06.06
AIDS Vaccine 2012
Posters
Association of Interleukin-10 Promoter Genetic
Variants with T-Cell and B-Cell Activation in HIV-1
Infection
D. Naicker 1 , B. Julg 2 , C. McClurg 2 , M. Ghebremichael 2 ,
F. Porichis 2 , J. Zupkosky 2 , M. Jaggernath 1 , M. Mokgoro 1 ,
P. Goulder 3 , B. Walker 2 , D. Kaufmann 2 , T. Ndung’u 1
1 HIV Pathogenesis Programme, Durban, South Africa; 2 Ragon
Institute of MGH, MIT and Harvard, Boston, MA, USA;
3 University of Oxford, Department of Paediatrics, United
Kingdom, United Kingdom (Great Britain)
Background: Interleukin-10 (IL-10) is a potent immunoregulatory
cytokine, with promoter polymorphisms that have previously
been associated with HIV-1 susceptibility and pathogenesis.
Association of IL-10 SNPs with markers of CD4, CD8 and B cell
activation has not previously been investigated.
Methods: Two IL-10 polymorphisms were genotyped by TaqMan
allelic discrimination and markers of activation of CD4, CD8 and
B cells were measured in 63 individuals using flow cytometry.
The following monoclonal antibody combinations were used:
anti-CD3 Pac-blue, anti-CD38 PE-Cy7, anti-HLA-DR ACP-Cy7, anti-
CD95 PE, anti-CD19 Alexa-700, anti-IgG PE-Cy5, anti-PD-1 APC,
anti-Ki67 FITC, anti-CD4 Qdot605 and anti-CD8 Qdot655.
Results: Previous studies on this cohort showed a significant
association between -1082GG and higher median IL-10 expression,
compared to the -1082AA/AG (p= 0.0006). The -592AA and
-1082AA (both previously shown to be associated with low-IL-10
production) had significantly higher median expression of HLA-
DR on CD4 and CD8 cells respectively, compared to the other
genotypes (-592AA vs. -592CA p= 0.005, -592AA vs. -592CC p=
0.03 and -1082AA vs. -1082AG p= 0.02). The -592AA genotype also
had a higher median expression of CD95 and PD-1 on CD4 cells
(-592AA vs. -592CA p= 0.0227, -592AA vs. -592CC p= 0.0270 and
-592AA vs. -592CA p= 0.01 respectively). The -592CC and -1082GG
genotypes associated with higher median expression of IgG on the
surface of B cells (-592CC vs. -592AA p= 0.0207 and -1082GG vs.
-1082AG p= 0.0392, -1082GG vs. -1082AA p= 0.0051).
Conclusion: These data suggest that IL-10 polymorphisms that
affect cytokine production and HIV pathogenesis may affect
markers of immune activation and exhaustion in response to
antigen, and suggest a beneficial role for IL-10 in chronic HIV
infection. Further studies on association between IL-10 and the
quality and magnitude of immune responses in HIV infection
are needed.
179
POSTERS