3rd International AIDS Society Conference on HIV Pathogenesis and Treatment Rio de Janeiro - July 24 - 27, 2005

HOST GENETICS, VIRAL SEQUENCE DIVERSITY AND ANTIVIRAL CELLULAR AND HUMORAL IMMUNITY IN HIV-1 CLADE B INFECTED INDIVIDUALS IN PERU

IAS Conf HIV Pathog Treat 2005 Jul 24-27;3rd: Abstract No. TuOa0104

Zuniga R.¹, Lucchetti A.¹, Galvan P.¹, Sanchez S.¹, Peinado J.¹, Frahm N.², Linde C.², Hewitt H.², Hildebrand W.H.³, Montefiori D.⁴, Allen T.², Altfeld M.², Walker B.D.², Sanchez J.¹, Brander C.^2
1Asociación Civil IMPACTA Salud y Educación, Lima, Peru, ²Partners AIDS Research Center, Boston, MA, United States of America, ³University of Oklahoma, Oklahoma City, OK, United States of America, ⁴Laboratory for AIDS Vaccine Research & Development, Duke University Medical, Durham, NC, United States of America

HIV vaccine design will crucially depend on detailed knowledge of circulating viral HIV strains, host population genetics and immune correlates of controlled HIV infection. To better define these factors and to guide effective vaccine design, we studied neutralizing antibody activity, CD4 and CD8 T cell-mediated immune responses and viral diversity in a cohort of 63, high-resolution HLA typed and HIV 1 clade B-infected individuals enrolled in Lima, Peru. The cohort was composed of young adults (median age 31 years), mostly individuals at high risk for HIV infection (MSM and partners of infected individuals); with a median CD4 count of 379 (201-1035) cells/µL and viral load of 4.75 (1.69 — 6) log₁₀ RNA copies/mL, predominantly treatment naïve and chronically infected. Total HIV-specific T responses assessed by γ-IFN ELISPOT and Intracellular Cytokine Staining (ICS) were dominantly directed against Nef (71% of all individuals showing responses), RT (68%) and p24 (61%) viral proteins. Gag-specific CD8 T cell responses, measured by ELISPOT and ICS were directly correlated to higher CD4 counts. The CD4 response pattern differed from that seen in previously published studies in clade B infection, likely reflecting the unique genetic background of this population, with a high frequency (27%) of the A02/B035/Cw04 haplotype. This allele combination has found earlier to be associated with elevated viral burden and may explain the relatively high viral set points observed in this widely untreated cohort. In addition, a potent neutralizing activity against HIV-1 strain SF162 and variable neutralizing activity against heterologous primary isolates was observed in 40 individuals tested. Together, this is the first study to combine a detailed assessment of nAb, CTL and Th-cell responses, viral sequence analysis and host genetics to guide HVI vaccine design and highlight the importance of defining these factors for the design of potential vaccine candidates.

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Basic | TuOa0104 | Rosario Zuniga
13.7 543 13.7 Monitoring anti-HIV immune responses

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