PMID- 27627692
OWN - NLM
STAT- MEDLINE
DCOM- 20171017
LR  - 20201209
IS  - 1557-8100 (Electronic)
IS  - 1536-2310 (Linking)
VI  - 20
IP  - 10
DP  - 2016 Oct
TI  - Rolling out Efavirenz for HIV Precision Medicine in Africa: Are We Ready for 
      Pharmacovigilance and Tackling Neuropsychiatric Adverse Effects?
PG  - 575-580
AB  - The introduction of antiretroviral therapy (ART) led to huge reductions in human 
      immunodeficiency virus (HIV)-related deaths, turning HIV-infection into a chronic 
      condition. Attention is now turning to quality of life for patients on lifelong 
      ART treatment, reflecting on the safety of antiretroviral drugs. In sub-Saharan 
      Africa, efavirenz (EFV) forms the preferred first-line ART but adverse drug 
      events have also been reported. We express our concern on EFV-based regimens 
      being part of mass rollout programs without full attention to toxicities. EFV is 
      associated with various neuropsychiatric adverse events (AEs). If EFV use is not 
      monitored, a huge burden of neuropsychiatric AEs and elevated risk of drug 
      resistance due to nonadherence are likely to follow. A monumental EFV-based ART 
      regimen rollout program, through the UNAIDS 90-90-90 and option B plus 
      programs/approaches, is planned, which will more than double the number of 
      patients on EFV-containing ART. According to this ambitious treatment target, by 
      2020, 90% of all people living with HIV will know their HIV status; 90% of all 
      people with diagnosed HIV infection will receive sustained ART; and 90% of all 
      people receiving ART will have viral suppression. On the other hand, HIV patients 
      of African origin are predisposed to developing EFV-induced neuropsychiatric AEs 
      due to specific CYP2B6 genetic variants causing impaired metabolism of EFV. It is 
      our considered opinion that the potential quantitative and qualitative burden of 
      EFV-induced neuropsychiatric AEs, which can vary from person-to-person and 
      between populations, deserve special attention and action during the ART rollout 
      program. We here make a case for Africa in particular where we project the burden 
      of neuropsychiatric AEs to be greatest. We advocate for surveillance of 
      neuropsychiatric AEs due to EFV therapy, incorporation of pharmacogenetics 
      testing for CYP2B6 to assist in EFV dosing, and measurement of plasma EFV 
      concentration, as a three-pronged rational therapeutic drug monitoring strategy 
      to guide EFV treatment toward precision medicine.
FAU - Masimirembwa, Collen
AU  - Masimirembwa C
AD  - 1 Department of Drug Metabolism and Pharmacokinetics & Medical Analytics, African 
      Institute of Biomedical Science and Technology , Harare, Zimbabwe .
AD  - 2 Division of Clinical Pharmacology, Department of Medicine, University of Cape 
      Town , Cape Town, South Africa .
FAU - Dandara, Collet
AU  - Dandara C
AD  - 3 Division of Human Genetics, Department of Pathology, Faculty of Healthy 
      Sciences, Institute of Infectious Disease and Molecular Medicine, University of 
      Cape Town , Cape Town, South Africa .
FAU - Leutscher, Peter Derek Christian
AU  - Leutscher PD
AD  - 4 Centre of Clinical Research, Regional Hospital North Denmark, Clinical 
      Institute Aalborg University , Aalborg, Denmark .
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20160914
PL  - United States
TA  - OMICS
JT  - Omics : a journal of integrative biology
JID - 101131135
RN  - 0 (Alkynes)
RN  - 0 (Anti-Retroviral Agents)
RN  - 0 (Benzoxazines)
RN  - 0 (Cyclopropanes)
RN  - JE6H2O27P8 (efavirenz)
SB  - IM
MH  - Africa South of the Sahara
MH  - Alkynes
MH  - Anti-Retroviral Agents/adverse effects/*therapeutic use
MH  - Benzoxazines/adverse effects/*therapeutic use
MH  - Cyclopropanes
MH  - Drug Monitoring
MH  - Drug Resistance, Viral
MH  - HIV Infections/*drug therapy
MH  - Humans
MH  - Mental Disorders/chemically induced
MH  - Patient Compliance
MH  - *Pharmacogenomic Variants
MH  - Precision Medicine
MH  - Quality of Life
EDAT- 2016/09/15 06:00
MHDA- 2017/10/19 06:00
CRDT- 2016/09/15 06:00
PHST- 2016/09/15 06:00 [pubmed]
PHST- 2017/10/19 06:00 [medline]
PHST- 2016/09/15 06:00 [entrez]
AID - 10.1089/omi.2016.0120 [doi]
PST - ppublish
SO  - OMICS. 2016 Oct;20(10):575-580. doi: 10.1089/omi.2016.0120. Epub 2016 Sep 14.