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The HLA-B*5701 Allele Is Highly Enriched in Brazilian Elite Controllers
Maria Teresa Maidana Giret*1, E Bermudez-Aza1, H Tomiyama1, M Melillo Sauer1, D Watkins2, and E Kallas1,3
1Federal Univ of Sao Paulo, Brazil; 2Univ of Wisconsin, US; and 3Univ of Sao Paulo, Brazil
Background: Some rare HIV-1-infected individuals,
referred to as elite controllers, have persistently undetectable plasma viral
load in the absence of therapy. These individuals likely mount successful
immune responses to the virus, but the mechanisms of this control remain
unclear. Several studies examining HLA associations with disease progression
have suggested that certain HLA class I alleles, such as HLA-B*57,
are associated with low set-point viremia and delayed onset of AIDS. The aims
of this study were to determine the HLA allele distribution in elite
controllers who were recently infected in Sao Paulo, Brazil. Brazilian patients
express a mixture of HLA alleles reflecting the diverse groups of individuals
that populated this country. Additionally, there are several different strains
of viruses circulating in South America.
Methods: We performed HLA class I molecular
typing on a cohort of recently HIV-1-infected subjects identified by STARHS
(Serologic Testing Algorithm for Recent HIV Seroconverters). We also analyzed T
cell counts and HIV-1 viral load.
Results: Of the 197 participants, 92.1% were men and
their median age was 31.5 years (25 to 75%, IQR 25.2 to 37.0). The median CD4+
T cell count was 535 cells/mm3 (IQR 420 to 699) and the viral load was
18,600 HIV RNA copies/mL (IQR 4115 to 63,350). The most common HLA
alleles were HLA-A*0201 (46%), -B*1510 (18%) and -B*3520
(18%), and -Cw*0701 (34%). We identified 7 (3.5%) elite controllers (viral load
<400 copies/mL and CD4+ T cell counts >400 cells/μL) based
on viral load assessments throughout their follow-up (median 429.7 days). Of
the elite controllers, 5 (71.4%) were HLA-B*5701 positive, whereas only 3
of the normal progressors were positive for this allele (n = 43). Overall,
the HLA-B*5701 allele was strongly correlated with elite controller
status (p <0.001).
Conclusions: We have identified 5 HLA-B*5701-positive
elite controllers in a cohort of patients who were recently infected with HIV-1.
This allele was highly enriched in our elite controllers, suggesting that HLA-B*5701
plays an important role in control of viral replication, even in heterogeneous
populations infected with diverse strains of HIV-1.
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