8th Annual Conference Of The British HIV Association [BHIVA]


19 – 21 April 2002, University of York, York


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[TITLE:] SEQUENTIAL TRANSMISSION OF HIV-1 CONTAINING DRUG RESISTANCE-ASSOCIATED MUTATIONS

[AUTHOR(S):] S Taylor1,2, P Cane1, S. Hue1, L Xu1, T Win3, Y Lie3, N Hellman3, C Petropoulos3, J Workman1, D Ratcliffe1 and D Pillay1
1 PHLS Antiviral Susceptibility Reference Unit, University of Birmingham, UK, 2 Department of Sexual Medicine, Birmingham Heartlands Hospital, UK, and 3 Virologic, South San Francisco, CA, USA

BHIVA Conf 2002 Apr 19-21;8:O9


OBJECTIVE: We have investigated a potential transmission chain of drug-resistant HIV-1 between three individuals over a 5-year period.

METHODS: Sequencing of the pol, env and gag genes from these three individuals and 25 other geographically and temporally related samples was performed. Phylogenetic analysis was undertaken to provide molecular support for the transmission events. Genotypic and recombinant phenotypic analysis was performed to identify resistance-associated mutations, drug susceptibility and replicative capacity. Clonal analysis of env genes from blood and seminal plasma virus was undertaken to assess the impact of compartmentalization of virus at the time of sexual transmission.

RESULTS: Viruses containing the reverse transcriptase drug resistance-associated mutations M41L, E44D, L210W, and T215D were transmitted sequentially between three homosexual men (A, B and C). They persisted in person B for at least 4 years, despite intermittent therapy and reduced viral replicative capacity, compared with wildtype strains. The likelihood of sequential transmission was supported by both epidemiological and phylogenetic evidence. Clonal analysis of the V3 loop of the env gene from semen and blood virus suggested that virus transmitted to patient C was of the syncytium-inducing phenotype and originated from the genital tract, rather than blood of person B.

CONCLUSIONS: Our data suggest that variants with drug-resistance associated mutations can persist within newly infected individuals, despite intervening antiretroviral therapy and can subsequently be sexually transmitted.

PRESENTING AUTHOR: S Taylor

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Copyright © 2002 - British HIV Association (BHIVA) Reproduction of this abstract (other than one copy for personal reference) must be cleared through the BHIVA Organising Secretariat 1 Mountview Court, 310 Friern Barnet Lane, London N20 0LD