Impact of Efavirenz Metabolism on Loss to Care in Older HIV+ Africans

  • Jessie TorgersenEmail author
  • Scarlett L. Bellamy
  • Bakgaki Ratshaa
  • Xiaoyan Han
  • Mosepele Mosepele
  • Athena F. Zuppa
  • Marijana Vujkovic
  • Andrew P. Steenhoff
  • Gregory P. Bisson
  • Robert Gross
Original Research Article


Background and Objective

Efavirenz is commonly used in Africa and is frequently associated with neurocognitive toxicity, which may compromise clinical outcomes. Older individuals are at increased risk for drug toxicity and clinical outcomes may be worse in older age, particularly among those individuals with cytochrome P450 (CYP) 2B6 polymorphisms associated with slower efavirenz metabolism. The aim of this study was to determine if the CYP2B6 polymorphisms differentially impacts loss to care in older people.


We conducted a prospective cohort study of 914 treatment-naïve HIV+ adults initiating efavirenz-based antiretroviral treatment at public HIV clinics in Gaborone, Botswana between 2009 and 2013. Older age, defined as age ≥ 50 years, was the primary exposure and loss to care at 6 months was the primary outcome. Interaction between age and CYP2B6 516G>T and 983T>C polymorphisms, defined as extensive, intermediate, and slow metabolism, was assessed. Neurocognitive toxicity was measured using a symptom questionnaire. Age-stratified logistic regression was performed to identify factors associated with loss to care.


Older age was associated with loss to care (OR 1.95, 95% CI 1.30–2.92). Age modified the effect of CYP2B6 genotype on loss to care with older, slow metabolizers at over four-fold higher risk when compared to older, intermediate metabolizers (OR 4.06 95% CI 1.38–11.89); neurocognitive toxicity did not mediate this risk. CYP2B6 metabolism genotype did not increase risk of loss to care in younger participants.


Older age was associated with loss to care, especially among those with slow efavirenz metabolism. Understanding the relationship between older age and CYP2B6 genotype will be important to improving outcomes in an aging population initiating efavirenz-based ART in similar settings.



We would like to thank the patients who participated in this study and medical staff at the Bontleng, Broadhurst 3, Broadhurst Traditional Area, Morwa, Nkoyaphiri, Phase II, and Village Infectious Diseases Care Clinics for their assistance with this endeavor. We are grateful to the Ministry of Health of Botswana for supporting this project.

Compliance with Ethical Standards

Conflict of Interest

The authors declare there is no conflict of interest.


United States National Institute of Mental Health (R01 MH080701) and Penn Center for AIDS Research (P30 MH097488) and Penn Mental Health AIDS Research Center (P30 AI 045008) both NIH-funded programs.

Ethical Standards

The parent study was approved by the Institutional Review Board at the University of Pennsylvania and by the Botswana Ministry of Health. Informed consent was obtained from all participants included in this study. Funding agencies had no involvement in the analysis, interpretation of results, or development of this manuscript.


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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Jessie Torgersen
    • 1
    • 2
    Email author
  • Scarlett L. Bellamy
    • 3
  • Bakgaki Ratshaa
    • 4
  • Xiaoyan Han
    • 2
  • Mosepele Mosepele
    • 5
  • Athena F. Zuppa
    • 6
  • Marijana Vujkovic
    • 6
  • Andrew P. Steenhoff
    • 4
    • 6
  • Gregory P. Bisson
    • 1
    • 2
  • Robert Gross
    • 1
    • 2
  1. 1.Department of Medicine, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA
  2. 2.Department of Biostatistics, Epidemiology, and Informatics, Center for Clinical Epidemiology and Biostatistics, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA
  3. 3.Department of Epidemiology and BiostatisticsDrexel University Dornsife School of Public HealthPhiladelphiaUSA
  4. 4.Botswana UPenn PartnershipGaboroneBotswana
  5. 5.Faculty of MedicineUniversity of BotswanaGaboroneBotswana
  6. 6.Department of PediatricsChildren’s Hospital of PhiladelphiaPhiladelphiaUSA

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