Low concordance and resistance mutation emergence in the HIV protease gene among circulating and cell-associated viruses at viral replication episodes during darunavir/ritonavir monotherapy

Authors

  • A Torres-Cornejo,

    1. Service of Infectious Diseases, Microbiology and Preventive Medicine, University Hospital Virgen del Rocío, Biomedicine Institute of Sevilla (IBiS), University Hospital Virgen del Rocío/CSIC/University of Sevilla, Seville, Spain
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    • These authors contributed equally to this work.
  • OJ Benmarzouk-Hidalgo,

    1. Service of Infectious Diseases, Microbiology and Preventive Medicine, University Hospital Virgen del Rocío, Biomedicine Institute of Sevilla (IBiS), University Hospital Virgen del Rocío/CSIC/University of Sevilla, Seville, Spain
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    • These authors contributed equally to this work.
  • A Gutierrez-Valencia,

    1. Service of Infectious Diseases, Microbiology and Preventive Medicine, University Hospital Virgen del Rocío, Biomedicine Institute of Sevilla (IBiS), University Hospital Virgen del Rocío/CSIC/University of Sevilla, Seville, Spain
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  • R Ruiz-Valderas,

    1. Service of Infectious Diseases, Microbiology and Preventive Medicine, University Hospital Virgen del Rocío, Biomedicine Institute of Sevilla (IBiS), University Hospital Virgen del Rocío/CSIC/University of Sevilla, Seville, Spain
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  • P Viciana,

    1. Service of Infectious Diseases, Microbiology and Preventive Medicine, University Hospital Virgen del Rocío, Biomedicine Institute of Sevilla (IBiS), University Hospital Virgen del Rocío/CSIC/University of Sevilla, Seville, Spain
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  • LF López-Cortés

    Corresponding author
    1. Service of Infectious Diseases, Microbiology and Preventive Medicine, University Hospital Virgen del Rocío, Biomedicine Institute of Sevilla (IBiS), University Hospital Virgen del Rocío/CSIC/University of Sevilla, Seville, Spain
    • Correspondence: Dr Luis F. López-Cortés, Unidad Clínica de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospital Universitario Virgen del Rocío, Av. Manuel Siurot, s/n. 41013, Sevilla, Spain. Tel: +34 955013096; fax: +34 954624466; e-mail: lflopez@us.es

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  • This work was presented in part at the International AIDS Society Conference, Washington, DC, USA, 23–27 July 2012 (Poster LBPE21).

Abstract

Objective

To assess the changes on the HIV protease gene in plasma and peripheral blood mononuclear cell (PBMC) compartments during viral replication episodes in patients on boosted-darunavir monotherapy (mtDRV/rtv).

Methods

A prospective study was carried out in which adult HIV-1-infected patients who started mtDRV/rtv after viral suppression for ≥6 months with no major darunavir-related resistance mutations were enrolled. Patients with two consecutive plasma HIV RNA measurements > 200 HIV-1 RNA copies/mL were considered as having virological failure (VF), while patients with two consecutive plasma HIV RNA measurements > 50 copies/mL without meeting the VF criteria were considered to have virological rebound (VR). HIV protease genotypic profiles from plasma and PBMCs were performed at baseline and at VF and VR episodes.

Results

One hundred and fifty patients were included in the study, with overall VF and VR rates of 14% (n = 21) and 14.7% (n = 22), respectively. No major darunavir resistance mutations were observed in the plasma or PBMC samples. Circulating and cell-associated viruses showed a wild-type protease gene sequence in 54% and 23% of patients, respectively while the remainder patients only harboured minor protease inhibitor-associated mutations. Full concordance between plasma RNA and PBMC DNA protease genotypes was found in 23% of the sequences.

Conclusions

No darunavir-related mutations were found in patients with VF or VR, either in plasma or in PBMCs; thus, simplification to mtDRV/rtv does not comprise future antiretroviral treatment options.

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