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Amplification of Near Full-length HIV-1 Proviruses for Next-Generation Sequencing
Published on: October 16, 2018
Persistence of multidrug-resistant HIV-1 in primary infection leading to superinfection
Bluma Brenner1, Jean-Pierre Routy, Yudong Quan
1McGill University AIDS Centre, Jewish General Hospital and McGill University Health Centre, Montreal, Quebec, Canada.
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.
Insights
Multidrug-resistant (MDR) HIV-1 infections can persist for years in primary HIV-1 infection (PHI) cases, with one instance of MDR superinfection observed. Genotypic analysis in PHI is crucial for identifying MDR infections and superinfections impacting treatment outcomes.
Area of Science:
- Virology
- Immunology
- Infectious Diseases
Background:
- Previous studies documented multidrug resistance (MDR) persistence in primary HIV-1 infection (PHI) for 1-2 years without treatment.
- This study investigates the long-term evolution of transmitted wild-type (WT), drug-resistant, and MDR HIV-1 infections.
Purpose of the Study:
- To characterize the evolutionary dynamics of transmitted HIV-1 infections (WT, resistant, MDR) in PHI.
- To document the long-term persistence of MDR HIV-1 infections and identify instances of superinfection.
Main Methods:
- Genotypic analysis of viral quasi-species over 1.5-7 years in 31 PHI patients.
- Sequencing of reverse transcriptase and protease regions to identify resistance mutations.
- Phylogenetic and clonal analysis to confirm superinfection.
Main Results:
- Little viral quasi-species evolution observed (>99.6% homology) for over 1.5 years in WT, resistant, and MDR infections.
- Transmitted resistance mutations persisted for 2-7 years; MDR infections showed long-term persistence.
- One case of MDR superinfection was confirmed, where an initial MDR infection was cleared and replaced by a second MDR strain.
Conclusions:
- Genotypic analysis in PHI is valuable for identifying superinfections and MDR infections.
- MDR infections and superinfections are significant factors influencing virological and treatment outcomes in PHI.
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