Page 248 - HIVMED_v21_i1.indb

Southern African Journal of HIV Medicine
ISSN: (Online) 2078-6751, (Print) 1608-9693
Page 1 of 4 Scientific Letter

Drug resistance after cessation of efavirenz-based

antiretroviral treatment started in pregnancy

Authors: Background: To reduce risk of antiretroviral resistance when stopping efavirenz (EFV)-based
Globahan Ajibola 1 antiretroviral treatment (ART), staggered discontinuation of antiretrovirals (an NRTI tail) is
Christopher Rowley 1,2,3
Dorcas Maruapula 1 recommended. However, no data directly support this recommendation.
Jean Leidner 4
Kara Bennett 5 Objectives: We evaluated the prevalence of HIV drug resistance mutations in pregnant women
Kathleen Powis 1,2,6,7 living with HIV who stopped efavirenz (EFV)/emtricitabine (FTC)/tenofovir disoproxil
Roger L. Shapiro 1,2,3 fumarate (TDF) postpartum.
Shahin Lockman 1,2,8
Method: In accordance with the prevailing Botswana HIV guidelines at the time, women with
Affiliations: pre-treatment CD4 > 350 cells/mm , initiated EFV/FTC/TDF in pregnancy and stopped ART
3
1 Botswana Harvard T.H. Chan
School of Public Health AIDS at 6 weeks postpartum if formula feeding, or 6 weeks after weaning. A 7-day tail of FTC/TDF
Initiative Partnership, was recommended per Botswana guidelines. HIV-1 RNA and genotypic resistance testing
Gaborone, Botswana (bulk sequencing) were performed on samples obtained 4–6 weeks after stopping EFV.
Stanford HIV Drug Resistance Database was used to identify major mutations.
2 Department of Immunology
and Infectious Diseases, Results: From April 2014 to May 2015, 74 women who had stopped EFV/FTC/TDF enrolled,
Harvard T.H. Chan School of with median nadir CD4 of 571 cells/mm . The median time from cessation of EFV to sample
3
Public Health, Boston, United draw for genotyping was 5 weeks (range: 3–13 weeks). Thirty-two (43%) women received a
States
1-week tail of FTC/TDF after stopping EFV. HIV-1 RNA was available from delivery in 70 (95%)
3 Beth Israel Deaconess women, 58 (83%) of whom had undetectable delivery HIV-1 RNA (< 40 copies/mL). HIV-1 RNA
Medical Center, Boston, was available for 71 women at the time of genotyping, 45 (63%) of whom had HIV-1 RNA < 40
United States copies/mL. Thirty-five (47%) of 74 samples yielded a genotype result, and four (11%) had a major
drug resistance mutation: two with K103N and two with V106M. All four resistance mutations
4 Goodtables Data Consulting,
LLC., Norman, United States occurred among women who did not receive an FTC/TDF tail (4/42, 10%), whereas no mutations
occurred among 18 genotyped women who had received a 1-week FTC/TDF tail (p = 0.053).
5 Bennett Statistical Conclusions: Viral rebound was slow following cessation of EFV/FTC/TDF in the postpartum
Consulting, Inc., Ballston
Lake, United States period. Use of an FTC/TDF tail after stopping EFV was associated with the lower prevalence
of subsequent NNRTI drug resistance mutation.
6 Department of Medicine,
Division of General Internal Keywords: drug resistance; resistance mutations; HIV; antiretroviral treatment; Botswana.
Medicine, Massachusetts
General Hospital, Boston,
United States Introduction
7 Department of Pediatrics Cessation of antiretrovirals raises concerns about the potential for the development of
and Pediatric Surgery, drug-resistant viral strains, particularly for non-nucleoside reverse transcriptase inhibitors
Massachusetts General (NNRTIs). Non-nucleoside reverse transcriptase inhibitors, such as efavirenz (EFV), have long
Hospital, Boston,
United States half-lives and a low barrier to the development of drug resistance. When used in combination
with other classes of drugs such as nucleoside reverse transcriptase inhibitors (NRTIs), staggered
8 Division of Infectious discontinuation using a 4–7-day ‘tail’ of the NRTI backbone when stopping NNRTI-based
Disease, Brigham and antiretroviral treatment (ART) is advised. This is believed to mitigate the unintended period of
1
Women’s Hospital, Boston, monotherapy with NNRTIs that ensues because of the long half-life of most drugs in this class,
United States
thus reducing the risk of developing drug resistance. There are, however, very limited data to
2,3
directly support this recommendation for a tenofovir disoproxil fumarate (TDF)/emtricitabine
(FTC) ‘tail’: following cessation of EFV. Of note, pharmacokinetic variability (linked genetic
factor – CYP2B6) in EFV metabolism between individuals has been observed, and EFV levels may
Corresponding author: Globahan Ajibola, [email protected]
Project research number: R01HD061265
Read online: Dates: Received: 19 Aug. 2019 | Accepted: 16 Sept. 2019 | Published: 27 Jan. 2020
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to read online. Note: For editorial commentary from Prof. Gary Maartens (University of Cape Town) on this article, please see: https://doi.org/10.4102/
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