HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa ; KwaZulu-Natal Research Institute for Tuberculosis and HIV, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa ; Institute of Infectious Disease and Molecular Medicine, and the Division of Medical Virology, University of Cape Town and National Health Laboratory Services, Cape Town, South Africa ; Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, Canada ; British Columbia Centre for Excellence in HIV/AIDS, Vancouver, British Columbia, Canada.
PLoS One. 2013 Aug 28;8(8):e71758. doi: 10.1371/journal.pone.0071758. eCollection 2013.
Use of antiretroviral-based microbicides for HIV-1 prophylaxis could introduce a transmission barrier that inadvertently facilitates the selection of fitter viral variants among incident infections. To investigate this, we assessed the in vitro function of gag-protease and nef sequences from participants who acquired HIV-1 during the CAPRISA 004 1% tenofovir microbicide gel trial.
We isolated the earliest available gag-protease and nef gene sequences from 83 individuals and examined their in vitro function using recombinant viral replication capacity assays and surface protein downregulation assays, respectively. No major phylogenetic clustering and no significant differences in gag-protease or nef function were observed in participants who received tenofovir gel versus placebo gel prophylaxis.
Results indicate that the partial protective effects of 1% tenofovir gel use in the CAPRISA 004 trial were not offset by selection of transmitted/early HIV-1 variants with enhanced Gag-Protease or Nef fitness.
使用基于抗逆转录病毒的杀微生物剂预防 HIV-1 可能会引入一种传播屏障，无意中促进了在新发生的感染中选择更适应的病毒变异体。为了研究这一点，我们评估了在 CAPRISA 004 1%替诺福韦避孕凝胶试验中感染 HIV-1 的参与者的 gag-蛋白酶和 nef 序列的体外功能。
我们从 83 名个体中分离出最早获得的 gag-蛋白酶和 nef 基因序列，并分别使用重组病毒复制能力测定和表面蛋白下调测定来检测它们的体外功能。在接受替诺福韦凝胶与安慰剂凝胶预防的参与者中，未观察到 gag-蛋白酶或 nef 功能的主要系统发育聚类或显著差异。
结果表明，在 CAPRISA 004 试验中，1%替诺福韦凝胶的部分保护作用并未因选择具有增强的 Gag-蛋白酶或 Nef 适应性的传播/早期 HIV-1 变异体而抵消。
