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AIDS Res Hum Retroviruses. 2018 Aug;34(8):667-671. doi: 10.1089/AID.2017.0135. Epub 2018 Jun 12.

Prevalence of Rilpivirine and Etravirine Resistance Mutations in HIV-1 Subtype C-Infected Patients Failing Nevirapine or Efavirenz-Based Combination Antiretroviral Therapy in Botswana.

Author information

1
1 Botswana Harvard AIDS Institute Partnership , Gaborone, Botswana .
2
2 Department of Medical Laboratory Sciences, Faculty of Health Sciences, University of Botswana , Gaborone, Botswana .
3
3 Harvard T.H. Chan School of Public Health , Department of Immunology and Infectious Diseases, Boston, Massachusetts.
4
4 Centre for Public Health Initiatives, University of Pennsylvania , Philadelphia, Pennsylvania.
5
5 Lady Davis Institute for Medical Research, McGill University , Montreal, Canada .
6
6 Rutgers Global Health Institute, Rutgers Biomedical and Health Sciences, Rutgers University , New Brunswick, New Jersey.

Abstract

Rilpivirine (RPV) and Etravirine (ETR) are approved second-generation non-nucleoside reverse transcriptase inhibitors (NNRTIs) for HIV treatment. There is a cross-resistance HIV mutation profile between first- and second-generation NNRTI drugs. We determined the prevalence of HIV-1 drug resistance mutations (DRMs) to RPV and ETR in Botswana. A total of 168 HIV-1 polymerase gene sequences from participants failing nevirapine (NVP)- or efavirenz (EFV)-containing regimens were analyzed for DRMs using the Stanford University HIV drug resistance database. Forty-one sequences were from an adult antiretroviral therapy (ART) study, the Tshepo study, and 127 from a prevention of mother-to-child transmission (PMTCT) study, the Mashi study, all conducted in Botswana. Prevalence of RPV and ETR highest DRM in the adult ART study (nā€‰=ā€‰41) were K101E (26.2%), E138A (23.8%), and Y181C (26.2%). The PMTCT cohort's (nā€‰=ā€‰127) high prevalence mutations were Y181C (15.7%), E138A (15%), and K101E (11%). A total of 42.9% and 3.2% of patients in the adult ART study and PMTCT study, respectively, had three or more NNRTI mutations at virologic failure. We identified HIV-1 mutations conferring resistance to RPV and ETR even though they have not been used in Botswana. Of concern was the high proportion of sequences from the adult ART study that displayed multiple DRMs; as the number of NNRTI mutations increases, the level of cross-resistance increases. It is plausible that patients displaying such profiles maybe at increased risk of failing second-generation NNRTI drugs, hence, calls for genotyping in patients with prior NVP or efavirenz exposure before prescription of RPV- or ETR-containing cART.

KEYWORDS:

drug resistance; efavirenz; etravirine; nevirapine; rilpivirine

PMID:
29732907
PMCID:
PMC6079649
[Available on 2019-08-01]
DOI:
10.1089/AID.2017.0135

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