Bautista, CT

Currier, JR

Hoelscher, M

Kijak, GH

Kim, JH

Koehler, RN

Maboko, L

McCutchan, FE

Michael, NL

Moqueet, N

Ratto-Kim, S

Robb, ML

Saathoff, E

Walsh, AM

English

PubMed

RN Koehler

AM Walsh

E Saathoff

JR Currier

CT Bautista

N Moqueet

S Ratto-Kim

L Maboko

M Hoelscher

ML Robb

NL Michael

FE McCutchan

JH Kim

GH Kijak

Crossref

S011-05 OA. HLA-A*7401 is associated with protection from HIV-1 acquisition and disease progression in Mbeya, Tanzania

McCutchan FE

Michael NL

Robb ML

Hoelscher M

Maboko L

Ratto-Kim S

Moqueet N

Bautista CT

Currier JR

Saathoff E

Walsh AM

Koehler RN

Kim JH

Kijak GH

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Retrovirology

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Retrovirology
Open AccessOral presentation
S011-05 OA. HLA-A*7401 is associated with protection from HIV-1 
acquisition and disease progression in Mbeya, Tanzania
RN Koehler*1, AM Walsh1, E Saathoff2, JR Currier1, CT Bautista1, 
N Moqueet1, S Ratto-Kim1, L Maboko3, M Hoelscher2, ML Robb1, 
NL Michael4, FE McCutchan1, JH Kim4 and GH Kijak1
Address: 1US Military HIV Research Program/Henry M Jackson Foundation, Rockville, MD, USA, 2Dept. of Infectious Diseases & Tropical Medicine, 
Univ. of Munich, Munich, Germany, 3Mbeya Medical Research Program, Mbeya, Tanzania and 4US Military HIV Research Program, WRAIR, 
Rockville, MD, USA
* Corresponding author    
Background
Genetic variation in class I HLA impacts the strength,
breadth, and depth of anti-HIV adaptive cellular immune
responses, while also influencing innate immunity via
interaction with killer immunoglobulin receptors (KIR)
on natural killer (NK) cells. Allele HLA-A*7401 is found
almost exclusively in sub-Saharan African populations
with little known about the immune responses it restricts.
The objective of this exploratory study was to investigate
the effects of HLA-A*7401 on disease progression and risk
of HIV-1 acquisition in an East African cohort population.
Methods
3,096 consented adults were enrolled in a prospective
cohort in Mbeya, Tanzania with semiannual follow-up for
42 months. Studied individuals included: HIV sero-preva-
lent at enrollment (n = 508), HIV sero-converters (n = 99)
and individuals remaining sero-negative (n = 174). Class
I HLA was genotyped using a high-throughput high-reso-
lution real-time PCR-based platform. CD4-cell counts
were determined cross-sectionally for sero-prevalent indi-
viduals at enrollment. Genetic and statistical analyses
were performed using PyPop and JMP.
Results
HLA-A*7401 carriers (13.8%) had a decreased risk of
HIV-1 acquisition compared to non-carriers (O.R. = 0.39;
95% C.I. = 0.17–0.88; p = 0.02). HLA-A*7401 showed no
significant effect on viral load set-point (p = 0.57). Among
HIV sero-prevalent cases, HLA-A*7401 was associated
with protection from disease progression (CD4-
counts<200 cells/ul) (O.R. = 3.91; 95% C.I. = 1.39–11.03;
p = 0.002; age-adjusted O.R. = 4.11; 95%C.I. = 1.62–
13.87; p = 0.002). This association remained significant
after controlling for linkage disequilibrium with HLA-B
and HLA-C alleles.
Conclusion
The protection from HIV acquisition and disease progres-
sion conferred by HLA-A*7401 in this exploratory study
could be due to direct and/or indirect effects. HLA-
A*7401 could be directly involved in NK-mediated innate
immune responses through interaction with KIR. Addi-
tionally, HLA-A*7401 may restrict adaptive immune
responses to an unknown pathogen, thus diminishing the
level of immune activation, and indirectly protecting from
HIV acquisition and disease progression. The implications
of these results on the design and evaluation of preventive
vaccines warrant further study to elucidate the involved
protective mechanisms.
from AIDS Vaccine 2009
Paris, France. 19–22 October 2009
Published: 22 October 2009
Retrovirology 2009, 6(Suppl 3):O2 doi:10.1186/1742-4690-6-S3-O2
<supplement> <title> <p>AIDS Vaccine 2009</p> </title> <editor>Anna Laura Ross</editor> <note>Meeting abstracts – A single PDF containing all abstracts in this Supplement is available <a href="http://www.biomedcentral.com/content/files/pdf/1742-4690-6-S3-full.pdf">here</a>.</note> <url>http://www.biomedcentral.com/content/pdf/1471-2105-10-S12-info.pdf</url> </supplement>
This abstract is available from: http://www.retrovirology.com/content/6/S3/O2
© 2009 Koehler et al; licensee BioMed Central Ltd. 


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S011-05 OA. HLA-A*7401 is associated with protection from HIV-1 acquisition and disease progression in Mbeya, Tanzania

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