15th International AIDS Conference Bangkok, Thailand - July 11-16, 2004

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. TuOrA1139)

McCutchan F, Piyasirisilp S, Hoffmann O, Sanders-Buell E, Wilson G, Tovanabutra S, Birx DL, Hoelscher M, Maboko L
Henry M. Jackson Foundation, Rockville, MD, United States

BACKGROUND: Dual infection with more than one HIV-1 subtype is a potential source of new recombinant strains and may result from limited cross-protective immunity. A high-risk cohort in Tanzania, where subtypes A, C, and D co-circulate, has been evaluated for dual infection.

METHODS: A subset of the cohort was evaluated using serial samples from 98 individuals obtained over the first 6 to 9 months of follow-up. HIV-1 genotyping was initiated with the Multiregion Hybridization Assay (MHAacd). In-depth analysis of the viral quasispecies was conducted by sequencing and analysis of a 1.4KB amplicon encompassing gag.

RESULTS: By MHAacd genotyping, subtypes C and AC recombinants predominated in this cohort and one out of four individuals showed evidence of dual infection, either by a shift in subtype over time or by simultaneous hybridization with two probes in a given region. Two putative dual infections and two cases without evidence for dual infection were further evaluated by sequencing 20 or more gag clones from each of two time points. Dual infection was confirmed in case 442, with subtype C three months after infection but subtype C and two different AC recombinants at 6 months. Case 529, a prevalent infection, had a single AC recombinant at 3 months but also other, related AC recombinants at 6 and 9 months. Two matched "control" cases harbored only a single subtype. Conclusion The MHAacd provided power to discriminate single and dual infections. Dual infections showed rapid temporal fluctuations in the viral quasispecies and shifting proportions of strains. The true proportion of dual infections may be difficult to establish with precision because of technical limitations, but it appears to be substantial in this high-risk cohort exposed to multiple subtypes. Natural infection may not always protect against a second subtype.

040711
TuOrA1139

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