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. 2015 Jan 30;10(1):e0117430.
doi: 10.1371/journal.pone.0117430. eCollection 2015.

HIV drug resistance mutations in proviral DNA from a community treatment program

Anne Derache  1 , Hyoung-Shik Shin  2 , Maya Balamane  1 , Elizabeth White  1 , Dennis Israelski  1 , Jeffrey D Klausner  3 , Alexandra H Freeman  4 , David Katzenstein  1
Affiliations

HIV drug resistance mutations in proviral DNA from a community treatment program

Anne Derache et al. PLoS One. .

Abstract

Background: Drug resistance mutations archived in resting memory CD4+ cells may persist despite suppression of HIV RNA to <50 copies/ml. We sequenced pol gene from proviral DNA among viremic and suppressed patients to identify drug resistance mutations.

Methods: The Peninsula AIDS Research Cohort study enrolled and followed over 2 years 120 HIV infected patients from San Mateo and San Francisco Counties. HIV-1 pol genotyping by bulk sequencing was performed on 38 DNA and RNA from viremic patients and DNA only among 82 suppressed patients at baseline. Antiretroviral susceptibility was predicted by HIVDB.stanford.edu.

Results: Among 120 subjects, 81% were on antiretroviral therapy and had been treated for a median time of 7 years. Thirty-two viremic patients showed concordant RNA and DNA genotypes (84%); the discordant profiles were mainly observed in patients with low-level viremia. Among suppressed patients, 21 had drug resistance mutations in proviral DNA (26%) with potential resistance to one, two or three ARV classes in 16, 4 and 1 samples respectively.

Conclusions: The high level of genotype concordance between DNA and RNA in viremic patients suggested that DNA genotyping might be used to assess drug resistance in resource-limited settings, and further investigation of extracted DNA from dried blood spots is needed. Drug resistance mutations in proviral DNA in 26% of subjects with less than 50 copies/ml pose a risk for the transmission of drug resistant virus with virologic failure, treatment interruption or decreased adherence.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Flow chart for the 120 patients enrolled in the study.
Fig 2
Fig 2. Neighbor Joining tree with 2-Kimura parameters and 1,000 replicates.
Ethnicities are represent with different color codes: blue = White, green = Hispanic, red = African American and black = Asian and others. Bootstrap values for transmission clusters are showed. Drug resistance mutations are also represented ● NRTI ■ NNRTI and ▲ PI.
See this image and copyright information in PMC

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