Journal of NeuroVirology

, Volume 22, Issue 3, pp 349–357 | Cite as

Central nervous system penetration effectiveness of antiretroviral drugs and neuropsychological impairment in the Ontario HIV Treatment Network Cohort Study

  • Adriana CarvalhalEmail author
  • M. John Gill
  • Scott L. Letendre
  • Anita Rachlis
  • Tsegaye Bekele
  • Janet Raboud
  • Ann Burchell
  • Sean B. Rourke
  • and the Centre for Brain Health in HIV/AIDS


Since the introduction of combination antiretroviral therapy (cART), the incidence of severe HIV-associated neurocognitive impairment has declined significantly, whereas the prevalence of the milder forms has increased. Studies suggest that better distribution of cART drugs into the CNS may be important in reducing viral replication in the CNS and in reducing HIV-related brain injury. Correlates of neuropsychological (NP) performance were determined in 417 participants of the Ontario HIV Treatment Cohort Study (OCS). All participants were on three cART drugs for at least 90 days prior to assessment. Multiple logistic and linear regression methods were used. Most participants were Caucasian men with mean age of 47 years. About two thirds had a nadir CD4+ T-cell count below 200 cells/μL and 92 % had an undetectable plasma HIV viral load. The median CNS penetration effectiveness (CPE) score was 7. Sixty percent of participants had neuropsychological impairment. Higher CPE values significantly correlated with lower prevalence of impairment in bivariate and multivariate analyses. In this cross-sectional analysis of HIV+ adults who had a low prevalence of comorbidities and were taking three-drug cART regimens, greater estimated distribution of cART drugs into the CNS was associated with better NP performance.


HIV CPE Antiretroviral Neuropsychological impairment 



The Ontario HIV Treatment Network Cohort Study is funded by the Ontario Ministry of Health and Long-Term Care, OHTN Chair in Biostatistics. Public Health Ontario (PHO) Laboratories for providing the viral load testing. The views and conclusion presented here are not necessarily those of PHO. Preliminary results of this work was previously presented at the 19th Conference in Retrovirus and Opportunistic Infections CROI 2012 (Paper # 484)––Seattle, WA, USA.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.


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Copyright information

© Journal of NeuroVirology, Inc. 2015

Authors and Affiliations

  • Adriana Carvalhal
    • 1
    • 2
    Email author
  • M. John Gill
    • 3
  • Scott L. Letendre
    • 4
  • Anita Rachlis
    • 5
    • 6
  • Tsegaye Bekele
    • 7
  • Janet Raboud
    • 8
    • 9
  • Ann Burchell
    • 7
    • 9
  • Sean B. Rourke
    • 1
    • 2
    • 10
  • and the Centre for Brain Health in HIV/AIDS
  1. 1.Department of PsychiatryUniversity of TorontoTorontoCanada
  2. 2.Li Ka Shing Knowledge InstituteSt. Michael’s HospitalTorontoCanada
  3. 3.Department of MedicineUniversity of CalgaryCalgaryCanada
  4. 4.HIV Neurobehavioural Research Center and Antiretroviral Research CenterUniversity of California San DiegoSan DiegoUSA
  5. 5.Sunnybrook Health Sciences CenterTorontoCanada
  6. 6.Department of MedicineUniversity of TorontoTorontoCanada
  7. 7.The Ontario HIV Treatment NetworkTorontoCanada
  8. 8.Toronto General Research InstituteUniversity Health NetworkTorontoCanada
  9. 9.Dalla Lana School of Public HealthUniversity of TorontoTorontoCanada
  10. 10.The CIHR Centre for REACH in HIV/AIDS (Research Evidence into Action for Community Health)TorontoCanada

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