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AIDS. 2004 Aug 20;18(12):1653-60.

Persistence of multidrug-resistant HIV-1 in primary infection leading to superinfection.

Author information

1
McGill University AIDS Centre, Jewish General Hospital and McGill University Health Centre, Montreal, Quebec, Canada.

Erratum in

  • AIDS. 2004 Oct 21;18(15):2107.

Abstract

OBJECTIVE:

The authors previous studies documented persistence of multidrug resistance (MDR) acquired in five primary HIV-1 infection (PHI) cases for 1-2 years in the absence of antiretroviral treatment. This study characterizes the evolution of transmitted wild-type (WT) (n = 15), resistant (n = 10), and MDR (n = 6) infections. Long-term persistence of MDR infections (2-7 years), leading to one observed MDR superinfection is documented.

METHODS:

Genotypic changes in circulating viral quasi-species were evaluated over 1.5-7 years in patients (n = 31) enrolled in the PHI study. Sequencing of reverse transcriptase and protease regions identified nucleotide substitutions in the viral quasi-species and mutations at sites implicated in resistance to antiretroviral drugs. Phylogenetic and clonal analysis were performed to confirm one observed superinfection.

RESULTS:

Patients acquiring WT, drug-resistant and MDR infections showed little quasi-species evolution (> 99.6% homology) for more than 1.5 years, regardless of route of transmission. Transmitted resistance mutations (other than 184V) persisted for 2-7 years. MDR persistence in two PHI cases contrasted with the corresponding rapid reversion of MDR infections to WT in their partners following treatment interruption. One MDR transmission eliciting low-level viremia resulted in clearance of the original MDR infection followed by re-infection with a second heterologous MDR strain from a different partner. Phylogenetic and clonal analysis of source and index partner confirmed the superinfection. Both MDR species showed approximately 13-fold reductions in replication capacity relative to the homologous WT strain isolated from the source partner.

CONCLUSIONS:

Genotypic analysis in PHI may identify superinfection and MDR infections that represent important determinants of virological and treatment outcome.

[Indexed for MEDLINE]

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