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

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.