AEGiS-15IAC: Long-term survivors in Nairobi: Complete HIV-1 RNA sequences and immunogenetic associations.

15th International AIDS Conference

Bangkok, Thailand - July 11-16, 2004

Long-term survivors in Nairobi: Complete HIV-1 RNA sequences and immunogenetic associations.

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. TuOrA1106)

Weiser B, Burger H, Fang G, Kuiken C, Rowland-Jones S, Plummer F, Chen CH, Kaul R, Sinsheimer JS, Anzala AO, Bwayo J, Kimani J, Philpott S, Kitchen C, Gaschen B, Lang D, Shi B, Kemal KS, Rostran T, Brunner C
Wadsworth Center, NY State Department of Health

BACKGROUND: The pace of HIV-1 disease progression is variable, and long-term survival may be influenced by viral sequences, host genetics, and immune responses.

METHODS: To investigate the determinants of slow disease progression in an untreated African cohort infected with non-clade B HIV-1, we obtained complete plasma HIV-1 genomic sequences and immunogenetic profiles from six long-term survivors (LTS) in the Nairobi female sex worker cohort.

RESULTS: Three women were infected with HIV-1 subtype A strains, one with subtype D, and two with intersubtype recombinant genomes (A-C and D-C). Computational analyses did not reveal any discernible sequence changes likely to cause attenuation, although the Vpr R77Q mutation was found in three of the subjects. The CCR2-V64I polymorphism, previously linked to slow disease progression, was detected in four of six women. All four women bearing the V64I mutation also carried the HLA B58 allele, an association that has not previously been noted. To investigate the relationship between these two immunogenetic alleles, we expanded our analysis to include a group of 99 HIV-1-infected women from the same Nairobi cohort; this analysis demonstrated a highly significant association between V64I and HLA B58 (P=0.0012). Conclusion These data suggest that the CCR2-V64I allele may affect the pace of HIV-1 infection in part or entirely through the HLA B58 haplotype. They also may help to elucidate the mechanism by which the CCR2-V64I mutation slows disease progression; although multiple studies have reported the CCR2-V64I allele is associated with LTS, the mechanism by which it acts is still unclear. Future studies need to focus on the interaction of host immunogenetic factors with viral genomes from all HIV-1 subtypes in slowing disease progression.

Keywords: AEGIS, HIV-1, HIV Infections, Base Sequence, Disease Progression, Acquired Immunodeficiency Syndrome, HIV Long-Term Survivors, Immunogenetics, Prostitution, Survivors, HIV-1 Reverse Transcriptase, Alleles, Humans, Female, genetics, immunology

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TuOrA1106