Modest nonadherence to antiretroviral therapy promotes residual HIV-1 replication in the absence of virological rebound in plasma

Alexander O. Pasternak, Marijn de Bruin, Suzanne Jurriaans, Margreet Bakker, Ben Berkhout, Jan M. Prins, Vladimir V. Lukashov

Research output: Contribution to journalArticle

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Abstract

Background. Modern antiretroviral therapy (ART) regimens are widely assumed to forgive modest nonadherence, because virological suppression in plasma is common at adherence levels of >70%. Yet, it is unknown whether human immunodeficiency virus type 1 (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 40 patients (median duration of successful ART before study initiation, 46 months), whose 1-week adherence to therapy prior to the sampling moments was measured electronically.

Results. Patients were constantly 100% adherent (the optimal-adherence group), demonstrated improving adherence over time (the improving-adherence group), or neither of the above (the poor-adherence group). Adherence never decreased to <70% in any patient, and no rebound in plasma virological levels was observed. Nevertheless, poor adherence but not optimal or improving adherence caused a significant longitudinal increase in cell-associated HIV RNA levels (P = .006). Time-weighted changes and regression slopes of viral RNA load for the poor-adherence group were significantly higher than those for the optimal-adherence group (P < .01).

Conclusions. Because ART only blocks infection of new cells but not viral RNA transcription in cells infected before therapy initiation, the observed effects strongly suggest that modest nonadherence can cause new cycles of HIV-1 replication that are undetectable by commercial plasma viral load assays.
Original languageEnglish
Pages (from-to)1443-1452
Number of pages10
JournalThe journal of infectious diseases
Volume206
Issue number9
Early online date20 Aug 2012
DOIs
Publication statusPublished - Nov 2012

Fingerprint

Virus Replication
HIV-1
Viral RNA
Viral Load
RNA
Satellite Viruses
Therapeutics
HIV
DNA
Infection

Keywords

  • adult
  • anti-HIV agents
  • antiretroviral therapy, highly active
  • DNA, viral
  • female
  • HIV infections
  • HIV-1
  • humans
  • longitudinal studies
  • male
  • medication adherence
  • middle aged
  • plasma
  • RNA, viral
  • viral load

Cite this

Modest nonadherence to antiretroviral therapy promotes residual HIV-1 replication in the absence of virological rebound in plasma. / Pasternak, Alexander O.; de Bruin, Marijn; Jurriaans, Suzanne; Bakker, Margreet; Berkhout, Ben; Prins, Jan M.; Lukashov, Vladimir V.

In: The journal of infectious diseases, Vol. 206, No. 9, 11.2012, p. 1443-1452.

Research output: Contribution to journalArticle

Pasternak, Alexander O. ; de Bruin, Marijn ; Jurriaans, Suzanne ; Bakker, Margreet ; Berkhout, Ben ; Prins, Jan M. ; Lukashov, Vladimir V. / Modest nonadherence to antiretroviral therapy promotes residual HIV-1 replication in the absence of virological rebound in plasma. In: The journal of infectious diseases. 2012 ; Vol. 206, No. 9. pp. 1443-1452.
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