Seventh International Congress on Drug Therapy in HIV Infection Glasgow, UK - 14-17 November 2004

Int Cong Drug Therapy HIV 2004 Nov 14-18;7:Abstract No. PL2.3

Mark A. Wainberg , Dan Turner , Bluma Brenner , Daniella Moisi , Maureen Oliveira , Jean Pierre Routy
McGill University AIDS Centre, Jewish General Hospital, Montreal, Canada

We performed a longitudinal analysis to characterize the differential evolution of transmitted wild-type (WT) and drug resistant infections over time in primary HIV infection (PHI).

We evaluated genotypic changes over time (2-6 years) in 31 PHI subjects. Sequencing of RT and PR regions identified all nucleotide substitutions as well as mutations at sites implicated in resistance to antiretroviral drugs. Phylogenetic analysis was performed to test for superinfection following PHI.

Patients acquiring WT (n= 15), drug-resistant (n= 10) or MDR infections (n=6) showed little quasispecies evolution with >99.6% nucleotide homology for 2 years years, regardless of route of transmission. Transmitted drug resistance mutations, (other than 184V) persisted over time. In six PHI cases, the transmitted MDR infections persisted in contrast to the rapid reversion of MDR infections to WT in two identified source partners following structured treatment interruption (STI). One MDR transmission eliciting low-level viremia resulted in superinfection by a second heterologous MDR strain from a different partner. Phylogenetic and clonal analysis of both source and index partner confirmed the superinfection. In cell culture, both transmitted MDR species in this case showed 13-fold reductions in replication capacity relative to the homologous WT strain isolated from the source partner after the STI. Our findings suggest that superinfection in PHI can occur but is a relatively rare event.

Recently infected persons harbour a single dominant viral species in their plasma and PBMCs that persists over several years. In the PHI setting, superinfection and MDR infections may be important determinants of virological and treatment outcome.

SESSION 2: TREATMENT STRATEGIES AND ORAL PAPERS

2004-11-14
PL2-3

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