非洲女性阴道细菌影响替诺福韦的抗HIV疗效
Title：
Vaginal bacteria modify HIV tenofovir microbicide efficacy in African women
Abstract：
Antiretroviral-based strategies for HIV prevention have shown inconsistent results in women. We investigated whether vaginal microbiota modulated tenofovir gel microbicide efficacy in the CAPRISA (Centre for the AIDS Program of Research in South Africa) 004 trial. Two major vaginal bacterial community types—one dominated by Lactobacillus (59.2%) and the other where Gardnerella vaginalis predominated with other anaerobic bacteria (40.8%)—were identified in 688 women profiled. Tenofovir reduced HIV incidence by 61% (P = 0.013) in Lactobacillus-dominant women but only 18% (P = 0.644) in women with non-Lactobacillus bacteria, a threefold difference in efficacy. Detectible mucosal tenofovir was lower in non-Lactobacillus women, negatively correlating with G. vaginalis and other anaerobic bacteria, which depleted tenofovir by metabolism more rapidly than target cells convert to pharmacologically active drug. This study provides evidence linking vaginal bacteria to microbicide efficacy through tenofovir depletion via bacterial metabolism.
All Authors：
Nichole R Klatt, Ryan Cheu, Kenzie Birse, Alexander S Zevin, Michelle Perner, Laura Noël-Romas, Anneke Grobler, Garrett Westmacott, Irene Y Xie, Jennifer Butler, Leila Mansoor, Lyle R McKinnon, Jo-Ann S Passmore, Quarraisha Abdool Karim, Salim S Abdool Karim, Adam D Burgener
First Authors：
Nichole R Klatt, Ryan Cheu, Kenzie Birse, Alexander S Zevin, Michelle Perner, Laura Noël-Romas, Adam D Burgener
Correspondence：
Nichole R Klatt, Adam D Burgener
内容要点：
1、女性阴道菌群通常由卷曲、惰性、加氏或詹氏乳杆菌中的一种占优；
2、替诺福韦作为一种预防HIV感染的暴露前药物，通常对男性而非女性有效；
3、在非洲进行的CAPRISA项目中，研究阴道中乳酸菌占优（407人，59.2%）的和阴道加德菌占优（281人，40.8%）的女性；
4、替诺福韦使前者的HIV发病率降低61%，而后者仅降低18%；
5、后者阴道黏膜中可检测到的替诺福韦（在目标细胞转为药理活性药物前即被代谢降解）更低，且与阴道加德菌及其他厌氧细菌负相关。