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

AIDS. 2004 Aug 20;18(12):1653-60. doi: 10.1097/01.aids.0000131377.28694.04.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS-Related Opportunistic Infections / genetics
  • AIDS-Related Opportunistic Infections / transmission*
  • Anti-HIV Agents / therapeutic use
  • Cohort Studies
  • Drug Resistance, Multiple, Viral
  • HIV Infections / drug therapy
  • HIV Infections / genetics
  • HIV Infections / transmission*
  • HIV Protease Inhibitors / therapeutic use
  • HIV-1
  • Humans
  • Mutation / genetics
  • Phylogeny
  • Reverse Transcriptase Inhibitors / therapeutic use
  • Sequence Homology, Nucleic Acid
  • Sexual Partners
  • Superinfection / genetics
  • Superinfection / transmission*
  • Viral Load


  • Anti-HIV Agents
  • HIV Protease Inhibitors
  • Reverse Transcriptase Inhibitors