AEGiS-08IAC: Virological risk factors for heterosexual transmission of HIV-1: influence of virus load and genetic determinants of pathogenicity.

8th International AIDS Conference


Amsterdam, Netherlands — July 19-24, 1992

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Virological risk factors for heterosexual transmission of HIV-1: influence of virus load and genetic determinants of pathogenicity.

Int Conf AIDS 1992 Jul 19-24; 8:We61 (abstract no. WeC 1086)
Simmonds P, Zhang LQ, Holmes EC, MacKenzie P, Brettle RP, Leigh Brown AJ; Dept of Medical Microbiology, Univ. Edinburgh.

AIMS: To investigate the influence of virus load and determinants of virus tropism and pathogenicity in the env gene, on the probability of transmission of HIV-1 by heterosexual contact. STUDY GROUP: Since 1985, a large cohort of HIV-1 infected individuals and their regular heterosexual partners have been followed up. Both index and contact patients are clinically monitored every 3-6 months, and blood samples are taken to carry out standard immunological and virological investigations. In five couples where transmission has occurred, such samples are available from both the contact and index patients for several years before and after the transmission event.

METHODS: Virus load (RNA) in the plasma of contacts is monitored by a competitive PCR using conserved sequences in the gag region. Sequences in the V3/C2/V4 region of env are sequenced using previously published nested PCR-based methods (Simmonds et al., J. Virol; 64: 864).

RESULTS: We have successfully used phylogenetic analysis of p17gag variants detected in heterosexual couples to confirm that transmission has occurred between individuals. In all cases studies, gag sequences are significantly more similar between known index and contact couples than they are to sequences from unrelated Edinburgh patients, and from previously published sequences. Sequences data in this region will enable us to define index/contact couples that is independent of patient history. To investigate risk factors for transmission, we have compared virus load and V3 sequences of samples from the index at the time of transmission with those taken from the same individual 2 years previously (patient control) and with samples from non-transmitting couples matches as closely as possible for other risk factors. The risk of heterosexual transmission is multifactorial, and is directly or indirectly correlated with plasma virus load. However, we have obtained evidence that the probability of transmission is increased in the presence of a specific sequence in the V3 loop of the env gene. Sequence variation in this region is known to influence tropism and replication rate of HIV, and other work from our group has produced evidence for specific selection for this sequence in the contact patient at the time of transmission.

Keywords: AEGIS, Viral Load, Heterosexuality, HIV-1, Genes, env, Risk Factors, Virus Replication, Polymerase Chain Reaction, Variation (Genetics), Human, transmission, virology, genetics, ICA8KWDaegis,viralload,heterosexuality,hiv-1,genes,env,riskfactors,virusreplication,polymerasechainreaction,variation(genetics),human,transmission,virology,genetics,ica8
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WeC1086

Copyright © 1992 - International AIDS Society (IAS). Reproduction of this abstract (other than one copy for personal reference) must be cleared through the IAS.