LB6. HIV-1-Specific CD8+ T-Cell Responses Contribute to the Differential HIV Disease Progression in HIV-1-Infected Individuals with Variable HLA-B35 Genotype

Abstract

E-mail Abstract Author

Add To Itinerary

Session

Search Abstracts

Program

Session 10 Oral Abstract Session
Late Breakers I
Session Time: Monday, 2 pm - 4 pm
Room 6E

3:15 LB6.

HIV-1-Specific CD8+ T-Cell Responses Contribute to the Differential HIV Disease Progression in HIV-1-Infected Individuals with Variable HLA-B35 Genotype
X. Jin*¹, X. Gao², M. Ramanathan, Jr.³, G. R. Deschenes³, G. Nelson², S. J. O’Brien⁴, D. D. Ho³, T. R. O’Brien⁵, and M. Carrington²
¹Univ. of Rochester Med. Ctr., NY; ²SAIC, NCI, Frederick, MD; ³Aaron Diamond AIDS Res. Ctr., Rockefeller Univ., New York, NY; ⁴NCI, NIH, Frederick, MD; and ⁵NCI, NIH Rockville, MD

Background: Our previous data indicate that HIV-1-infected individuals with certain HLA-B*35 allelic variants (B*3502/3503/3504/5301) (B*35-Px) have more rapid disease progression than those with the B*3501/3508 (B*35-PY). The mechanisms responsible for this phenomenon are not clear.
Methods: To examine whether cellular immune responses may differ according to the HLA-B*35 genotype, we quantified HIV-1-specific CD8+ T-cell (CTL) responses using an intracellular cytokine-staining assay in the 32 HIV-1-positive individuals who have the B*35 alleles.
Results: 75% had CTL responses to Pol, 69% to Gag, 50% to Nef, and 41% to Env. Although the magnitude of CTL responses did not differ between patients bearing the B*35-PY genotype and those bearing the B*35-Px genotypes, there was a highly significant inverse correlation (p = 0.009) between plasma HIV-1 RNA levels and the Gag-specific CTL numbers in individuals with B*35-PY, but not with B*35-Px. Furthermore, a negative correlation between CTL activity for each of the 4 HIV antigens and viral load was observed among individuals with B*35-PY, whereas the relationship was always positive for the B*35-Px group. While these correlations were not significant in most cases, a significant difference between the B*35-PY and B*35-Px groups in their correlation values for total CTL activity and viral load was observed (p <0.05).
Conclusions: Our data suggest that the viral-specific CTL may be protective against HIV disease progression in infected-individuals with the B*35-PY, but not the B*35-Px genotype.