[MOAA102] Characterization of human immunodeficiency virus type I in the acute/early phase of infection in the individuals who subsequently become viremia controllers

5th International AIDS Society Conference on HIV Pathogenesis and Treatment

Cape Town - July 19 - 22, 2009

CHARACTERIZATION OF HUMAN IMMUNODEFICIENCY VIRUS TYPE I IN THE ACUTE/EARLY PHASE OF INFECTION IN THE INDIVIDUALS WHO SUBSEQUENTLY BECOME VIREMIA CONTROLLERS

IAS Conf HIV Pathog Treat 2009 Jul 19-22;5th: Abstract No. MOAA102

T. Miura^1,2,3, Z. Brumme², C. Brumme², B. Block², M. Brockman², A. Trocha², F. Pereyra², D. Kaufmann², A. Iwamoto¹, H. Jessen⁴, E. Rosenberg², A. Kelleher⁵, M. Markowitz⁶, S. Little⁷, B. Walker^2,3, AIEDRP Network
¹Institute of Medical Science, University of Tokyo, Tokyo, Japan, ²Ragon Institute of MGH, MIT and Harvard, Charlestown, United States, ³Howard Hughs Medical Institute, Chevy Chase, United States, ⁴Jessen Praxis, Berlin, Germany, ⁵University of New South Wales, Sydney, Australia, ⁶Aaron Diamond AIDS Research Center, New York, United States, ⁷University of California at San Diego, San Diego, United States

BACKGROUND: The individuals who can control viremia to < 2,000 RNA copies/ml without antiretrovirals are called HIV- 1 controllers. Little is known about the viruses in the acute/early phase of infection in these subjects. Here we characterize these viruses in terms of viral sequences and replication capacity.

METHODS: We analyzed (1) HLA allele types, (2) autologous viral sequences, and (3) replication capacity of the chimeric viruses encoding gag-protease derived from the acute/early phase of HIV controllers after acute infection (< 2,000 RNA copies/ml, CAAI), and compared to those of progressors after acute infection (PAAI). All of the participants were followed-up for at least a year.

RESULTS: The frequency of the persons expressing “protective” HLA class I alleles (B13/B27/B51/B57) amongst the CAAI was 31.6% (6/19), which significantly lower than those in the chronic HIV-1 controllers (66.7%, p=0.0014), thereby indicating that the CAAI unlikely represent the majority of the chronic controllers. The chimeric viruses derived from the 16 clade B-infected CAAI displayed significantly lower replication capacity than those from the 20 PAAI (0.455 vs 0.659, p=0.0006). Viral sequencing from the 17 CAAI revealed that drug resistant mutations were more frequently seen compared to PAAI [6/17(35.3%) vs 10/81(12.3%), p=0.033]; notably, 3 of the 6 were multiple-class resistants that likely affect viral fitness; both of two B57+CAAI had T242N viral escape that also affect viral fitness; furthermore, excluding the individuals expressing protective alleles or infected with drug resistant strains, 50% of the CAAI(3/6) viruses had B57 footprint mutations(T242N/A146P), indicating that they acquired attenuated viruses from B57 + donors.

CONCLUSIONS: Persons who control HIV viremia after acute infection have reduced viral fitness, linked to Gag-Protease, which is attributable to the complex factors including fitness cost by de novo CTL escape mutations in the recipients, transmission of multiple-class drug resistant strains and transmission of the attenuated escape variants from B57+donors.

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2009-07-22
MOAA102
Oral Abstract Session: MOAA1 - Control of HIV by Cellular Immunity

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