Neurocognitive impairment in patients treated with protease inhibitor monotherapy or triple drug antiretroviral therapy

PLoS One. 2013 Jul 25;8(7):e69493. doi: 10.1371/journal.pone.0069493. Print 2013.

Abstract

Background: In patients who remain virologically suppressed in plasma with triple-drug ART a switch to protease inhibitor monotherapy maintains high rates of suppression; however it is unknown if protease inhibitor monotherapy is associated to a higher rate of neurocognitive impairment.

Methods: In this observational, cross-sectional study we included patients with plasma virological suppression (≥ 1 year) without concomitant major neurocognitive confounders, currently receiving for ≥ 1 year boosted lopinavir or darunavir as monotherapy or as triple ART. Neurocognitive impairment was defined as per the 2007 consensus of the American Association of Neurology. The association between neurocognitive impairment and protease inhibitor monotherapy, adjusted by significant confounders, was analysed.

Results: Of the 191 included patients--triple therapy: 96, 1-2 years of monotherapy: 40 and >2 years of monotherapy: 55--proportions (95% CI) with neurocognitive impairment were: overall, 27.2% (20.9-33.6); triple therapy, 31.6% (22.1-41.0); short-term monotherapy, 25.0% (11.3-38.7); long-term monotherapy: 21.4% (10.5-32.3); p = 0.38. In all groups, neurocognitive impairment was mildly symptomatic or asymptomatic by self-report. There were not significant differences in Global Deficit Score by group. In the regression model confounding variables for neurocognitive impairment were years on ART, ethnicity, years of education, transmission category and the HOMA index. Adjusted by these variables the Odds Ratio (95% CI) for neurocognitive impairment of patients receiving short-term monotherapy was 0.85 (0.29-2.50) and for long-term monotherapy 0.40 (0.14-1.15).

Conclusions: Compared to triple drug antiretroviral therapy, monotherapy with lopinavir/ritonavir or darunavir/ritonavir in patients with adequate plasma suppression was not associated with a higher rate of asymptomatic neurocognitive impairment than triple drug ART.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Dementia Complex / prevention & control*
  • AIDS Dementia Complex / psychology
  • AIDS Dementia Complex / virology
  • Adult
  • Antiretroviral Therapy, Highly Active*
  • Cross-Sectional Studies
  • Darunavir
  • Drug Administration Schedule
  • Drug Resistance, Viral / drug effects
  • Female
  • HIV Protease Inhibitors / therapeutic use*
  • HIV-1 / drug effects*
  • HIV-1 / physiology
  • Humans
  • Lopinavir / therapeutic use*
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Ritonavir / therapeutic use*
  • Sulfonamides / therapeutic use*
  • Viral Load / drug effects

Substances

  • HIV Protease Inhibitors
  • Sulfonamides
  • Lopinavir
  • Ritonavir
  • Darunavir

Grants and funding

This work was supported by grant PI10/00483, Fondo de Investigaciones Sanitarias, Insituto de Salúd Carlos III. Dr I. Pérez-Valero, Dr. M. Estébanez, Dr. F.X. Zamora and S. Monge are supported by Río Hortega fellowships financed by Fondo de Investigaciones Sanitarias. Dr. M. Lagarde is supported by a fellowship financed by Instituto de Investigación Hospital 12 de Octubre (i+12). Dr. J.R. Arribas is an investigator from the Programa de Intensificación de la Actividad Investigadora en el SNS (I3SNS). IdiPAZ AIDS and infectious diseases investigator group is partially supported by “Red de Investigación en SIDA” (AIDS Research Network) (RIS) RD07/0006/2007. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.