Scientific Letter

Drug resistance after cessation of efavirenz-based antiretroviral treatment started in pregnancy

Globahan Ajibola, Christopher Rowley, Dorcas Maruapula, Jean Leidner, Kara Bennett, Kathleen Powis, Roger L. Shapiro, Shahin Lockman
Southern African Journal of HIV Medicine | Vol 21, No 1 | a1023 | DOI: https://doi.org/10.4102/sajhivmed.v21i1.1023 | © 2020 Globahan Ajibola, Christopher Rowley, Dorcas Maruapula, Jean Leidner, Kara Bennett, Kathleen Powis, Roger L. Shapiro, Shahin Lockman | This work is licensed under CC Attribution 4.0
Submitted: 19 August 2019 | Published: 27 January 2020

About the author(s)

Globahan Ajibola, Botswana Harvard T.H. Chan School of Public Health AIDS Initiative Partnership, Gaborone, Botswana
Christopher Rowley, Botswana Harvard T.H. Chan School of Public Health AIDS Initiative Partnership, Gaborone, Botswana; and, Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, United States; and, Beth Israel Deaconess Medical Center, Boston, United States
Dorcas Maruapula, Botswana Harvard T.H. Chan School of Public Health AIDS Initiative Partnership, Gaborone, Botswana
Jean Leidner, Goodtables Data Consulting, LLC., Norman, United States
Kara Bennett, Bennett Statistical Consulting, Inc., Ballston Lake, United States
Kathleen Powis, Botswana Harvard T.H. Chan School of Public Health AIDS Initiative Partnership, Gaborone, Botswana; and, Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, United States; Department of Medicine, Division of General Internal Medicine, Massachusetts General Hospital, Boston, United States; and, Department of Pediatrics and Pediatric Surgery, Massachusetts General Hospital, Boston, United States
Roger L. Shapiro, Botswana Harvard T.H. Chan School of Public Health AIDS Initiative Partnership, Gaborone, Botswana; and, Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, United States; and, Beth Israel Deaconess Medical Center, Boston, United States
Shahin Lockman, Botswana Harvard T.H. Chan School of Public Health AIDS Initiative Partnership, Gaborone, Botswana; and, Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, United States; and, Division of Infectious Disease, Brigham and Women’s Hospital, Boston, United States


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Abstract

Background: To reduce risk of antiretroviral resistance when stopping efavirenz (EFV)-based antiretroviral treatment (ART), staggered discontinuation of antiretrovirals (an NRTI tail) is recommended. However, no data directly support this recommendation.

Objectives: We evaluated the prevalence of HIV drug resistance mutations in pregnant women living with HIV who stopped efavirenz (EFV)/emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) postpartum.

Method: In accordance with the prevailing Botswana HIV guidelines at the time, women with pre-treatment CD4 > 350 cells/mm3, initiated EFV/FTC/TDF in pregnancy and stopped ART at 6 weeks postpartum if formula feeding, or 6 weeks after weaning. A 7-day tail of FTC/TDF was recommended per Botswana guidelines. HIV-1 RNA and genotypic resistance testing (bulk sequencing) were performed on samples obtained 4–6 weeks after stopping EFV. Stanford HIV Drug Resistance Database was used to identify major mutations.

Results: From April 2014 to May 2015, 74 women who had stopped EFV/FTC/TDF enrolled, with median nadir CD4 of 571 cells/mm3. The median time from cessation of EFV to sample draw for genotyping was 5 weeks (range: 3–13 weeks). Thirty-two (43%) women received a 1-week tail of FTC/TDF after stopping EFV. HIV-1 RNA was available from delivery in 70 (95%) women, 58 (83%) of whom had undetectable delivery HIV-1 RNA (< 40 copies/mL). HIV-1 RNA was available for 71 women at the time of genotyping, 45 (63%) of whom had HIV-1 RNA < 40 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 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).

Conclusions: Viral rebound was slow following cessation of EFV/FTC/TDF in the postpartum period. Use of an FTC/TDF tail after stopping EFV was associated with the lower prevalence of subsequent NNRTI drug resistance mutation.


Keywords

drug resistance; resistance mutations; HIV; antiretroviral treatment; Botswana

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Crossref Citations

1. ‘Covering the tail’ after stopping efavirenz-based antiretroviral therapy
Gary Maartens
Southern African Journal of HIV Medicine  vol: 21  issue: 1  year: 2020  
doi: 10.4102/sajhivmed.v21i1.1036