Ajibola Globahan, Rowley Christopher, Maruapula Dorcas, Leidner Jean, Bennett Kara, Powis Kathleen, Shapiro Roger L, Lockman Shahin
Botswana Harvard T.H. Chan School of Public Health AIDS Initiative Partnership, Gaborone, Botswana.
Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, United States.
South Afr J HIV Med. 2020 Jan 27;21(1):1023. doi: 10.4102/sajhivmed.v21i1.1023. eCollection 2020.
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.
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.
In accordance with the prevailing Botswana HIV guidelines at the time, women with pre-treatment CD4 > 350 cells/mm, 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.
From April 2014 to May 2015, 74 women who had stopped EFV/FTC/TDF enrolled, with median nadir CD4 of 571 cells/mm. 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 ( = 0.053).
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.
为降低停止基于依非韦伦（EFV）的抗逆转录病毒治疗（ART）时出现抗逆转录病毒耐药性的风险，建议逐步停用抗逆转录病毒药物（核苷类逆转录酶抑制剂维持期）。然而，尚无数据直接支持这一建议。
我们评估了产后停止使用依非韦伦（EFV）/恩曲他滨（FTC）/替诺福韦酯（TDF）的感染HIV的孕妇中HIV耐药突变的流行情况。
根据当时博茨瓦纳现行的HIV指南，治疗前CD4>350个细胞/mm³的女性在孕期开始使用EFV/FTC/TDF，若采用配方奶喂养则在产后6周停止ART，若母乳喂养则在断奶后6周停止。根据博茨瓦纳指南，建议使用7天的FTC/TDF维持期。在停止使用EFV后4 - 6周采集的样本上进行HIV - 1 RNA和基因型耐药性检测（二代测序）。使用斯坦福HIV耐药数据库来识别主要突变。
2014年4月至2015年5月，74名停止使用EFV/FTC/TDF的女性入组，最低点CD4的中位数为571个细胞/mm³。从停止使用EFV到进行基因分型样本采集的中位时间为5周（范围：3 - 13周）。32名（43%）女性在停止使用EFV后接受了1周的FTC/TDF维持期。70名（95%）女性分娩时可获得HIV - 1 RNA，其中58名（83%）分娩时HIV - 1 RNA检测不到（<40拷贝/mL）。基因分型时71名女性可获得HIV - 1 RNA，其中45名（63%）HIV - 1 RNA<40拷贝/mL。74份样本中有35份（47%）获得了基因型结果，4份（11%）有主要耐药突变：2份为K103N，2份为V106M。所有4个耐药突变均发生在未接受FTC/TDF维持期的女性中（4/42，10%），而在接受了1周FTC/TDF维持期的18名基因分型女性中未发生突变（P = 0.053）。
产后停止使用EFV/FTC/TDF后病毒反弹缓慢。停止使用EFV后使用FTC/TDF维持期与后续非核苷类逆转录酶抑制剂耐药突变的较低流行率相关。
