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254 Class II HLA-DRB3 Discordance and Protection from HIV-1 Transmission
S. L. Hader*1, T. Hodge1, K. Buchacz2, R. Bray3, N. Padian4, A. Rausa5, S. Slaviniski1,5, and S. D. Holmberg1
1CDC, Atlanta, GA, USA; 2Univ. of California, Berkeley, USA; 3Emory Univ., Atlanta, GA, USA; 4Univ. of California, San Francisco, USA; and 5Mississippi State Dept. of Hlth., Jackson, USA
Background: Identification of immunologic factors that protect against HIV transmission may contribute to the design of effective HIV vaccines. Human leukocyte antigens (HLAs) are integrated into the viral envelope as HIV buds from host cells; these integrated HLAs could theoretically determine whether HIV is “rejected” by an exposed susceptible person (preventing transmission), much like tissue transplants are accepted or rejected based on HLA matching between donor and recipient.
Objective: To determine if HLA discordance (mismatching) is more frequent within partner-pairs in which HIV transmission has not occurred compared with those in which HIV transmission has occurred.
Methods: Partner-pairs in which at least 1 partner was HIV-infected and heterosexual exposure or transmission between partners had occurred were identified from 2 epidemiologic studies–a Mississippi HIV cluster investigation and the California Partners II Study. Class I (A, B, and C) and Class II (DRB1, DRB3, DRB4, DRB5, and DQB1) HLA-typing was performed on stored blood samples.
Results: Eight (35%) of 23 partner-pairs in which HIV transmission did not occur were immunologically discordant at HLA-DRB3, with DRB3 present in the HIV-infected donor partner and absent in the recipient partner, compared with 0 (0%) of 11 partner-pairs in which HIV transmission did occur (Fisher’s exact, p = 0.027). No differences in concordance at other HLA loci were observed.
Conclusions: Heterosexual partner-pairs in which HIV transmission did not occur were more frequently HLA-discordant at Class II DRB3, indicating a possible partial protective effect of HLA mismatching at DRB3. Further investigation of the roles of Class II HLAs in HIV transmission and as possible components of HIV vaccines should be pursued.
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