Samuel Reshmi, Julian Marc Noguera, Paredes Roger, Parboosing Raveen, Moodley Pravi, Singh Lavanya, Naidoo Anneta, Gordon Michelle
*Department of Virology, National Health Laboratory Service, University of KwaZulu-Natal, Durban, South Africa; †IrsiCaixa AIDS Research Institute, Badalona, Catalonia, Spain; ‡Universitat de Vic, Vic, Catalonia, Spain; §HIV Unit, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain; ∥Universitat Autonoma de Barcelona, Barcelona, Catalonia, Spain; and ¶Department of Virology, HIV Pathogenesis Laboratory, Nelson R Mandela Medical School, University of KwaZulu-Natal, Durban, South Africa.
J Acquir Immune Defic Syndr. 2016 Dec 1;73(4):384-389. doi: 10.1097/QAI.0000000000001116.
Antiretroviral drug resistance following pMTCT strategies remains a significant problem. With rapid advancements in next generation sequencing technologies, there is more focus on HIV drug-resistant variants of low frequency, or the so-called minority variants. In South Africa, AZT monotherapy for pMTCT, similar to World Health Organization option A, has been used since 2008. In 2010, a single dose of co-formulated TDF/FTC was included in the strategy for prevention of resistance conferred by single-dose nevirapine (sd NVP). The study was conducted in KwaZulu-Natal, South Africa, among pMTCT participants who received AZT monotherapy from 14 weeks of gestation, intrapartum AZT and sd NVP, and postpartum sd TDF/FTC. Twenty-six specimens collected at 6 weeks post-delivery were successfully sequenced using 454 ultra-deep sequencing. Non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance was detected in 17 of 26 (65%) patients, 2 (7%) had Thymidine analogue mutations, and 3 (11%) had K65R. Of the 17 patients with NNRTI resistance, 11 (65%) had high-level NNRTI resistance, whereas 6 (35%) had intermediate NNRTI resistance. The levels of NNRTI resistance are much higher than would be expected, given the inclusion of antepartum AZT and postpartum TDF/FTC. This high level of NNRTI resistance could impact future NNRTI-containing treatment for a large proportion of pMTCT-exposed women. The detection of Thymidine analogue mutations highlights the need to understand the clinical impact of these on AZT-containing antiretroviral treatment in women exposed to AZT monotherapy.
预防母婴传播（pMTCT）策略后的抗逆转录病毒药物耐药性仍然是一个重大问题。随着下一代测序技术的迅速发展，人们更加关注低频的HIV耐药变异体，即所谓的少数变异体。在南非，自2008年以来一直采用与世界卫生组织方案A类似的用于pMTCT的齐多夫定（AZT）单药疗法。2010年，单剂量复方替诺福韦酯/恩曲他滨（TDF/FTC）被纳入预防单剂量奈韦拉平（sd NVP）所致耐药性的策略中。该研究在南非夸祖鲁-纳塔尔省进行，研究对象为从妊娠14周开始接受AZT单药疗法、产时使用AZT和sd NVP以及产后使用sd TDF/FTC的pMTCT参与者。使用454超深度测序成功对分娩后6周采集的26份标本进行了测序。在26例患者中有17例（65%）检测到非核苷类逆转录酶抑制剂（NNRTI）耐药，2例（7%）有胸苷类似物突变，3例（11%）有K65R突变。在17例有NNRTI耐药的患者中，11例（65%）有高水平的NNRTI耐药，而6例（35%）有中度NNRTI耐药。考虑到产前使用了AZT和产后使用了TDF/FTC，NNRTI耐药水平远高于预期。这种高水平的NNRTI耐药可能会影响未来很大一部分接受过pMTCT治疗的妇女使用含NNRTI的治疗方案。胸苷类似物突变的检测凸显了了解这些突变对接受AZT单药疗法的妇女使用含AZT的抗逆转录病毒治疗的临床影响的必要性。
