320-W. Homozygosity for HLA-Bw4 Is Not Associated with Protection of HIV-1-Infected Persons of African Ancestry

Abstract

E-mail Abstract Author

Add To Itinerary

Session

Search Abstracts

Program

Session 51 Poster Session
Impact of Host Genetics on Viral Transmission and Disease Progression
Session Time: 4:30-6:30 pm
Room 4E-F

320-W.

Homozygosity for HLA-Bw4 Is Not Associated with Protection of HIV-1-Infected Persons of African Ancestry
R. A. Kaslow*¹, J. Tang¹, M.T. Dorak¹, S. Tang¹, R. Musonda², E. Karita³, C. Wilson^1,4, S. Allen^{1, and 3}
¹Univ. of Alabama, Birmingham; ²Zambia-UAB Project; ³Rwanda Project; and ⁴REACH Project

Background: In HIV-1+ Caucasians, homozygosity at the serogroup level for the Bw4 epitope has been associated with better control of HIV/AIDS. The association appeared independent of a number of reported markers of progression. Interaction between Bw4 and its natural killer (NK) cell receptor was suggested as a possible mechanism. We searched for a protective Bw4 effect in HIV-1+ persons of African ethnicity.
Methods: Class I HLA molecular typing has been performed on 228 Zambians, 202 Rwandans, and 203 African American adolescents. Associations of genetic determinants established elsewhere were observed here in cohort-specific analysis of HIV disease "control"—measured as earlier viral load (VL) in Zambians (clade C), as interval to appearance of clinical and hematologic abnormalities in Rwandans (clade A), and as categories of combined VL and CD4+ cell count in African Americans (clade B). Proportions of participants who carried 0, 1 (heterozygous), or 2 (homozygous) Bw4+ alleles were compared across disease control categories.
Results: Bw4+ alleles did not occur in successively higher proportions of participants with better disease control. In the presence or absence of B*57 (strongly protective in all 3 cohorts), homozygous Bw4+ Zambians did not have lower mean VL, homozygous Bw4+ Rwandans experienced no more benign course, and homozygous Bw4+ African Americans showed no more favorable VL/CD4+ cell combinations. In B*57-negatives, homozygous Bw4+ was found, respectively, in 9, 5, and 12% of Zambians with high, intermediate and low VL; in 20, 18, 20, and 12% of Rwandans with increasing intervals to recognition of abnormalities; and in 8, 12, and 0% of African Americans with progressively better virologic/immunologic control.
Conclusions: Homozygosity for Bw4 alleles did not protect against disease progression in 3 African groups infected with different viral subtypes. Confirmation that homozygosity for Bw4 protects Caucasians could imply important differences from ethnic Africans in control of HIV-1 infection through Bw4 modulation of CTL response or ligation with its specific NK cell receptor 3DL1.