HLA CLASS II ALLELE SHARING IN ZAMBIAN COUPLES: FROM MATE SELECTION TO HIV INFECTION

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TITLE: HLA CLASS II ALLELE SHARING IN ZAMBIAN COUPLES: FROM MATE SELECTION TO HIV INFECTION

Jianming (James) Tang,¹ Ana Penman–Aguilar,¹ Elena Lobashevsky,¹ M. Tevfik Dorak,¹ Isaac Zulu,² Grace Aldrovandi,¹ Susan Allen,¹ Richard A Kaslow.¹

¹Departments of Epidemiology, Medicine, and Pediatrics, University of Alabama at Birmingham, Birmingham, AL; ²School of Medicine, University of Zambia, Lusaka, Zambia

PCR–SSP– and sequencing–based genotyping of HLA–DRB1 and –DQB1 was performed in 251 Zambian couples participating in the Zambia–UAB HIV Research Project. At the 4–digit specificity level, the six most common DRB1 (*1101, *1503, *0302, *0301, *0701, and *1301) and DQB1 alleles (*0602, *0501, *0201, *0301, *0402, and *0604) accounted for 59.1% and 93.4% of the totals, respectively. Neither DRB1 nor DQB1 profiles differed by sex (p > 0.50 in global exact tests) or HIV seropositivity (p > 0.50). The frequencies of allele sharing between couples were 29.9% for DRB1 and 41.8% for DQB1, being consistent with those expected from random marriage. In contrast to earlier analyses of HLA class I data, the degree of class II allele and haplotype sharing was similar between HIV transmission pairs (both partners HIV+) and discordant pairs (p > 0.80). Heterogeneity in DRB1 allelic distribution was detected in 344 HIV seropositive Zambians categorized by low (<10,000 copies per mL of plasma), medium (10,000 to 100,000), and high (> 100,000) levels of viremia. Much of the DRB1 effect could be attributed to DRB1*1201 (p = 0.03, with adjustment for differences in age, gender, and duration of infection) as a favorable and DRB1*0102 (p = 0.09) as an unfavorable marker in this cohort. On the other hand, individual association of DQB1*0501 (n = 126) with reduced virus load (p = 0.01) did not lead to overall heterogeneity at the DQB1 locus. These findings indicate that HLA–DRB1 and –DQB1 alleles and haplotypes did not mediate mate selection or HIV–1 transmission in heterosexual Zambian couples. Nevertheless, several common class II alleles appeared to influence virus–host equilibration, albeit with reduced magnitudes of effects compared with HLA class I variants.