HIV-1 proviral resistance mutations: usefulness in clinical practice.

Kabamba-Mukadi, Benoît;Duquenne, Armelle;Henrivaux, P.;Musuamba Tshinanu, Flora;Goubau, Patrick;et.al.
(2010) HIV Medicine — Vol. 11, n° 8, p. 483-492 (2010)

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Authors
  • Duquenne, ArmelleUCLouvain
    Author
  • Henrivaux, P.
    Author
  • Musuamba Tshinanu, FloraUCLouvain
    Author
  • Ruelle, JeanUCLouvain
    Author
  • Author
  • Bodéus, MoniqueUCLouvain
    Author
  • Vandercam, BernardUCLouvain
    Author
  • Author
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Abstract
Objectives Transmitted HIV strains may harbour drug resistance mutations. HIV-1 drug resistance mutations are currently detected in plasma viral RNA. HIV-1 proviral DNA could be an alternative marker, as it persists in infected cells. Methods This was a prospective study assessing the prevalence and persistence of HIV-1 drug resistance mutations in DNA from CD4 cells before and after protease inhibitor (PI)- or nonnucleoside reverse transcriptase inhibitor (NNRTI)-based therapy initiation in 69 drug-naïve patients. Results Before therapy, 90 and 66% of detected mutations were present in CD4 cells and plasma, respectively. We detected seven key mutations, and four of these (M184M/V, M184M/I, K103K/N and M46M/I) were only found in the cells. When treatment was started, 40 patients were followed; the mutations detected at the naïve stage remained present for at least 1 year. Under successful treatment, new key mutations emerged in CD4 cells (M184I, M184M/I and Y188Y/H). Conclusions The proportion of mutations detected in the DNA was statistically significantly higher than that detected in standard RNA genotyping, and these mutations persisted for at least 1 year irrespective of therapy. The pre-existence of resistance mutations did not jeopardise treatment outcome when the drug concerned was not included in the regimen. Analysis of HIV-1 DNA could be useful in chronic infections or when switching therapy in patients with undetectable viraemia.
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Kabamba-Mukadi, B., Duquenne, A., Henrivaux, P., Musuamba Tshinanu, F., Ruelle, J., Yombi, J. C., Bodéus, M., Vandercam, B., & Goubau, P. (2010). HIV-1 proviral resistance mutations: usefulness in clinical practice. HIV Medicine, 11(8), 483-492. https://doi.org/10.1111/j.1468-1293.2009.00814.x (Original work published 2010)