Modest Nonadherence to Antiretroviral Therapy Promotes Residual HIV-1 Replication in the Absence of Virological Rebound in Plasma

A.O. Pasternak, M. de Bruin, S. Jurriaans, M. Bakker, B. Berkhout, J.M. Prins, V.V. Lukashov

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Abstract

Background. Modern antiretroviral therapy (ART) regimens are widely assumed to be forgivable to modest non-adherence, as virological suppression in plasma is common at adherence levels >70%. Yet, it is unknown whether HIV-1 replication is completely suppressed at these levels of adherence. Methods. We longitudinally quantified levels of cell-associated HIV-1 RNA and DNA in forty patients (median time on successful ART before the study initiation, 46 months), whose one-week adherence to therapy prior to the sampling moments was measured electronically. Results. Patients were either constantly 100% adherent, demonstrated improving adherence in time, or neither of the above (“poor adherers”). Adherence never fell below 70% in any patient, and no virological rebound in plasma was observed. Nevertheless, poor adherence, but not optimal or improving adherence, caused a significant longitudinal increase in cell-associated HIV RNA levels (P=0.006). Time-weighted changes and regression slopes of viral RNA were significantly higher in poor adherers than in optimal adherers (P
Original languageEnglish
Pages (from-to)1443-1452
JournalThe Journal of Infectious Diseases
Volume206
Issue number9
DOIs
Publication statusPublished - 2012

Keywords

  • protease inhibitor therapy
  • highly sensitive methods
  • t-cell-activation
  • infected individuals
  • viral suppression
  • immune activation
  • drug-resistance
  • viremia blips
  • adherence
  • rna

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    Pasternak, A. O., de Bruin, M., Jurriaans, S., Bakker, M., Berkhout, B., Prins, J. M., & Lukashov, V. V. (2012). Modest Nonadherence to Antiretroviral Therapy Promotes Residual HIV-1 Replication in the Absence of Virological Rebound in Plasma. The Journal of Infectious Diseases, 206(9), 1443-1452. https://doi.org/10.1093/infdis/jis502