Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, Washington, United States of America.
Department of Global Health, University of Washington, Seattle, Washington, United States of America.
PLoS One. 2022 Sep 27;17(9):e0275254. doi: 10.1371/journal.pone.0275254. eCollection 2022.
To assess in ART-naïve pregnant women randomized to efavirenz- versus raltegravir-based ART (IMPAACT P1081) whether pretreatment drug resistance (PDR) with minority frequency variants (<20% of individual's viral quasispecies) affects antiretroviral treatment (ART)-suppression at term.
A case-control study design compared PDR minority variants in cases with virologic non-suppression (plasma HIV RNA >200 copies/mL) at delivery to randomly selected ART-suppressed controls.
HIV pol genotypes were derived from pretreatment plasma specimens by Illumina sequencing. Resistance mutations were assessed using the HIV Stanford Database, and the proportion of cases versus controls with PDR to their ART regimens was compared.
PDR was observed in 7 participants (11.3%; 95% CI 4.7, 21.9) and did not differ between 21 cases and 41 controls (4.8% vs 14.6%, p = 0.4061). PDR detected only as minority variants was less common (3.2%; 95% CI 0.2, 11.7) and also did not differ between groups (0% vs. 4.9%; p = 0.5447). Cases' median plasma HIV RNA at delivery was 347c/mL, with most (n = 19/22) showing progressive diminution of viral load but not ≤200c/mL. Among cases with viral rebound (n = 3/22), none had PDR detected. Virologic non-suppression at term was associated with higher plasma HIV RNA at study entry (p<0.0001), a shorter duration of ART prior to delivery (p<0.0001), and randomization to efavirenz- (versus raltegravir-) based ART (p = 0.0085).
We observed a moderate frequency of PDR that did not significantly contribute to virologic non-suppression at term. Rather, higher pretreatment plasma HIV RNA, randomization to efavirenz-based ART, and shorter duration of ART were associated with non-suppression. These findings support early prenatal care engagement of pregnant women and initiation of integrase inhibitor-based ART due to its association with more rapid suppression of plasma RNA levels. Furthermore, because minority variants appeared infrequent in ART-naïve pregnant women and inconsequential to ART-suppression, testing for minority variants may be unwarranted.
在接受依非韦伦或拉替拉韦为基础的抗逆转录病毒治疗（ART）的初治孕妇中，评估治疗前耐药（PDR）与少数变异体（个体病毒准种的<20%）对妊娠期末的抗逆转录病毒治疗（ART）抑制的影响。
病例对照研究设计比较了分娩时病毒学未抑制（血浆 HIV RNA >200 拷贝/ml）的病例与随机选择的 ART 抑制对照组中 PDR 的少数变异体。
采用 Illumina 测序从治疗前血浆标本中提取 HIV pol 基因型。采用 HIV Stanford 数据库评估耐药突变，比较病例与对照组对其 ART 方案的 PDR 比例。
7 名参与者（11.3%；95%CI 4.7,21.9）出现 PDR，病例与对照组之间无差异（4.8% vs. 14.6%，p=0.4061）。仅作为少数变异体检测到的 PDR 较少见（3.2%；95%CI 0.2,11.7），两组之间也无差异（0% vs. 4.9%；p=0.5447）。病例分娩时的中位血浆 HIV RNA 为 347c/ml，其中大多数（n=19/22）显示病毒载量逐渐减少，但未降至≤200c/ml。在病毒反弹的病例中（n=3/22），无一例检测到 PDR。妊娠期末的病毒学未抑制与研究入组时较高的血浆 HIV RNA 相关（p<0.0001）、分娩前接受 ART 的时间较短（p<0.0001）以及随机接受依非韦伦（而非拉替拉韦）为基础的 ART 相关（p=0.0085）。
我们观察到中等频率的 PDR，但对妊娠期末的病毒学未抑制无显著影响。相反，较高的治疗前血浆 HIV RNA、随机接受依非韦伦为基础的 ART 以及 ART 时间较短与未抑制相关。这些发现支持孕妇早期进行产前保健并开始使用整合酶抑制剂为基础的 ART，因为它与更快速地抑制血浆 RNA 水平相关。此外，由于初治孕妇中的少数变异体出现频率较低，且对 ART 抑制无关紧要，因此检测少数变异体可能没有必要。
