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. 2020 Jan 27;21(1):1023.
doi: 10.4102/sajhivmed.v21i1.1023. eCollection 2020.

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

Globahan Ajibola  1 , Christopher Rowley  1   2   3 , Dorcas Maruapula  1 , Jean Leidner  4 , Kara Bennett  5 , Kathleen Powis  1   2   6   7 , Roger L Shapiro  1   2   3 , Shahin Lockman  1   2   8
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Free PMC article

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

Globahan Ajibola et al. South Afr J HIV Med. .
Free PMC article

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

Conflict of interest statement

The authors declare that no competing interests exist.

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References

    1. Lamorde M, Schapiro JM, Burger D, Back DJ. Antiretroviral drugs for prevention of mother-to-child transmission: Pharmacologic considerations for a public health approach. AIDS. 2014;28(17):2551–2563 10.1097/QAD.0000000000000439 - DOI - PubMed
    1. McIntyre JA, Hopley M, Moodley D, et al. . Efficacy of short-course AZT plus 3TC to reduce nevirapine resistance in the prevention of mother-to-child HIV transmission: A randomized clinical trial. PLoS Med. 2009;6(10):e1000172 10.1371/journal.pmed.1000172 - DOI - PMC - PubMed
    1. Chi BH, Sinkala M, Mbewe F, et al. . Single-dose tenofovir and emtricitabine for reduction of viral resistance to non-nucleoside reverse transcriptase inhibitor drugs in women given intrapartum nevirapine for perinatal HIV prevention: An open-label randomised trial. Lancet. 2007;370(9600):1698–1705. 10.1016/S0140-6736(07)61605-5 - DOI - PubMed
    1. Sinxadi PZ, Leger PD, McIlleron HM, et al. . Pharmacogenetics of plasma efavirenz exposure in HIV infected adults and children in South Africa. Br J Clin Pharmacol. 2015;80(1):146–156. 10.1111/bcp.12590 - DOI - PMC - PubMed
    1. Lockman S, Hughes M, Powis K, Ajibola G, Bennett K, Moyo S. Effect of co-trimoxazole on mortality in HIV-exposed but uninfected children in Botswana (the Mpepu Study): A double-blind, randomized, placebo-controlled trial. Lancet Glob Health. 2017;5(5):e491–e500. 10.1016/S2214-109X(17)30143-2 - DOI - PMC - PubMed

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