472 Co-receptor/HLA Class I Genetics and Cellular Immune Response in Patients with a Low Viral Set-point Ingrid Stahmer1, Jan van Lunzen 1, Jürgen Rockstroh2, Gerd Fätkenheuer3, Schlomo Staszewski4, Claus Schneider1, Thomas Eiermann1, Klara Tenner-Racz5, Paul Racz5, Hans-Jürgen Stellbrink*1 1Univ Hosp Eppendorf, Hamburg, Germany; 2Univ Hosp Bonn, Germany; 3Univ Hosp Cologne, Germany; 4Univ Hosp Frankfurt/Main, Germany; and 5Bernhard Nocht Inst for Tropical Med, Hamburg, Germany
Background: To assess the impact of genetic vs immunological factors on control of virus replication in subjects with low viral loads.
Methods: Within a prospective cohort (FITS) of 710 untreated HIV+ patients (pts), 34 subjects with viral load set points < 2,000 HIV RNA copies/ml were identified. HIV coreceptor (CCR5d32, CCR5 promoter A59029G, CCR2b) or ligand (SDF-1) mutations (CLM) were analyzed by PCR (n = 32). HLA class I haplotype was determined (n = 28), and CD4+/CD8+ gamma-IFN ELISpot was performed cross-sectionally and longitudinally during follow-up (n = 10 to date). Lymph node histology and in situ hybridization for HIV RNA were performed in 4 subjects. CTL responses were compared between lymph node (LNMC) and peripheral blood mononuclear cells (PBMC) in 1 subject.
Results: Twenty-three (23) out of 32 (72%) subjects had CLM associated with delayed progression; 15/32 [47%]) were either CCR5d32/wt or A59029G homozygous. HLA-B52 and B58 were slightly (9%), and HLA-B27 and B57 were markedly more frequent (18% and 24%, resp) than in an average Caucasian population or in a control group with > 2000 HIV RNA copies/ml (n = 68). These alleles were not more frequent in pts lacking CLM than in those with CLM. None of the subjects with CLM and a higher viral load in the control group was HLA-B27 or B57-positive. CTL ELISpot revealed limited but dominant responses to various peptides, which remained relatively stable during follow-up. CD4+ T-cell ELISpot showed broad responses to viral proteins and recall antigens, also in subjects with CLM. Lymph node histology and virus distribution were varied considerably between the subjects. Immunodominant CTL epitopes were identical between lymph node and peripheral blood.
Conclusions: These mutations known to restrict virus entry are important, but not sole determinants of a low viral set-point. Certain HLA class I alleles (namely HLA-B27 and B57) appear to contribute markedly to virus control. The cellular immune response appears comparably strong and broad in subjects with or without CLM and is detectable in both blood and lymph node.
