11th Conference on Retroviruses and Opportunistic Infections San Francisco, California - February 8 - 11, 2004

Conf Retrovir Opportunistic Infect 2004 Feb 8-11; 11:(abstract no. 11)

M M Addo¹, A Rathod¹, R Draenert¹, D Kaufmann¹, M R Perkins¹, C Verrill¹, M N Johnston¹, A G Wurcel¹, C Corcoran¹, J Braun², M Altfeld¹, S K Kalams³, S Buchbinder⁴, E S Rosenberg¹, B D Walker¹, and The HIV-1 controller study group
¹Partners AIDS Res. Ctr., Massachusetts Gen. Hosp., Boston, USA; ²Physicians Res. Network, New York, NY, USA; ³Vanderbilt Univ. Med. Ctr., Nashville, TN, USA; and ⁴San Francisco Dept. of Publ. Hlth., CA, USA

BACKGROUND: While the majority of HIV-1-infected individuals ultimately progress to disease, a minority of individuals spontaneously controls viral replication to low or undetectable levels in the absence of treatment (viral controllers), often for prolonged periods (HIV-1 long-term non-progressors [LTNP]). Understanding the correlates of immune protection in these individuals will provide important insights regarding HIV-1 pathogenesis and vaccine design. >b>

METHODS: We investigated 80 HIV-1-infected persons who spontaneously control plasma viremia below 2000 RNA copies/mL in the absence of therapy, and 24 untreated HIV-1 progressors as controls. Fresh PBMC were screened for T-cell responses using overlapping peptides spanning the entire expressed HIV-1 genome in IFN-γ ELISpot and intracellular cytokine staining assays. Maturation status of the immunodominant responses was investigated in a subset of study subjects using CCR7 and CD45RA monoclonal antibodies. HLA typing, chemokine receptor and GBV-C RNA status analysis were performed on all study subjects.

RESULTS: In spite of very similar viral loads, HIV controllers displayed a wide range of HIV-1 specific T-cell responses both in breadth (20 epitopic regions, range 2 to 48) and magnitude (4000 to 34,000 SFC/million PBMC). No statistically significant differences in breadth and magnitude of HIV-1-specific responses were observed between controllers and progressors. However, the number of individuals with terminally differentiated HIV-1-specific T-cell responses was higher in controllers compared to progressors. Multiple novel CTL epitopes were characterized. Those with factors known to be associated with enhanced immune control included 60% who expressed HLA B27 or B57, 22% with chemokine receptor mutations, 48% with concomitant GBV-C infection. For 25%, no factors associated with enhanced control were identified.

CONCLUSIONS: Robust CD8 T-cell responses can be detected in both HIV-1 controllers and progressors. Our data suggest that HIV-1-specific CD8 T cells of mature phenotype may be more easily detectable HIV controllers. A high proportion of individuals expressed HLA class I alleles associated with slow disease progression, indicating that control of viral replication may be at least partially CD8+ T-cell mediated, but others had weak to undetectable responses. These data indicate that viral controllers are a heterogeneous group, and that multiple factors may influence long-term containment of viremia.

040208
11

Copyright © 2004 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed (AIDSLINE) from National Library of Medicine.