开始使用醋酸甲羟孕酮长效注射剂的HIV-1血清阴性肯尼亚女性的阴道微生物群和免疫介质变化
Changes in Vaginal Microbiota and Immune Mediators in HIV-1-Seronegative Kenyan Women Initiating Depot Medroxyprogesterone Acetate.
作者信息
Roxby Alison C, Fredricks David N, Odem-Davis Katherine, Ásbjörnsdóttir Kristjana, Masese Linnet, Fiedler Tina L, De Rosa Stephen, Jaoko Walter, Kiarie James N, Overbaugh Julie, McClelland R Scott
机构信息
Departments of *Medicine;†Microbiology, University of Washington, Seattle, WA;‡Division of Vaccine and Infectious Disease, Fred Hutchinson Cancer Research Center, Seattle, WA;Departments of §Biostatistics;‖Global Health;¶Epidemiology; and#Laboratory Medicine, University of Washington, Seattle, WA;Departments of **Medical Microbiology;††Obstetrics and Gynaecology, University of Nairobi, Nairobi, Kenya;‡‡Kenyatta National Hospital, Nairobi, Kenya; and§§Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA.
出版信息
J Acquir Immune Defic Syndr. 2016 Apr 1;71(4):359-66. doi: 10.1097/QAI.0000000000000866.
BACKGROUND
Depot medroxyprogesterone acetate (DMPA) is associated with HIV acquisition. We studied changes in vaginal microbiota and inflammatory milieu after DMPA initiation.
METHODS
In a cohort of HIV-negative Kenyan women, we collected monthly vaginal swabs over 1 year before and after DMPA. Using quantitative polymerase chain reaction, we compared quantities of Lactobacillus crispatus, Lactobacillus jensenii, Lactobacillus iners, Gardnerella vaginalis, and total bacterial load (16S ribosomal RNA gene levels). Six vaginal immune mediators were measured with enzyme-linked immunosorbent assay. Trends in the detection and quantity of bacteria were estimated by logistic and linear mixed-effects regression.
RESULTS
From 2010 to 2012, 15 HIV-seronegative women initiated DMPA, contributing 85 visits (median, 6 visits/woman; range, 3-8 visits/woman). The median time of DMPA-exposed follow-up was 8.4 months (range, 1.5-11.6 months). Seven women (46%) had bacterial vaginosis within 70 days before DMPA start. L. iners was detected in 13 women (87%) before DMPA start, but other lactobacilli were rarely detected. Gardnerella vaginalis decreased by 0.21 log10 copies per swab per month after DMPA exposure (P = 0.01). Total bacterial load decreased by 0.08 log10 copies per swab per month of DMPA (P = 0.02). Sustained decreases in interleukin (IL)-6 (P = 0.03), IL-8 (P = 0.04), and IL-1 receptor antagonist (P < 0.001) were also noted. Nine women (60%) had L. crispatus detected post-DMPA, which significantly correlated with reduced IL-6 (P < 0.01) and IL-8 (P = 0.02).
CONCLUSIONS
Initiation of DMPA led to sustained shifts in vaginal bacterial concentrations and levels of inflammatory mediators. Further studies are warranted to outline components of the vaginal microbiota influenced by DMPA use and impact on HIV susceptibility.
背景
醋酸甲羟孕酮长效注射剂（DMPA）与HIV感染有关。我们研究了开始使用DMPA后阴道微生物群和炎症环境的变化。
方法
在一组HIV阴性的肯尼亚女性中，我们在开始使用DMPA之前和之后的1年里每月收集阴道拭子。使用定量聚合酶链反应，我们比较了卷曲乳杆菌、詹氏乳杆菌、惰性乳杆菌、阴道加德纳菌的数量以及总细菌载量（16S核糖体RNA基因水平）。通过酶联免疫吸附测定法测量六种阴道免疫介质。通过逻辑和线性混合效应回归估计细菌检测和数量的趋势。
结果
2010年至2012年，15名HIV血清阴性女性开始使用DMPA，共进行了85次随访（中位数，每名女性6次随访；范围，每名女性3 - 8次随访）。DMPA暴露后的随访中位时间为8.4个月（范围，1.5 - 11.6个月）。7名女性（46%）在开始使用DMPA前70天内患有细菌性阴道病。在开始使用DMPA前，13名女性（87%）检测到惰性乳杆菌，但很少检测到其他乳杆菌。暴露于DMPA后，阴道加德纳菌每月每拭子减少0.21 log10拷贝（P = 0.01）。DMPA使用期间，总细菌载量每月每拭子减少0.08 log10拷贝（P = 0.02）。还注意到白细胞介素（IL）-6（P = 0.03）、IL-8（P = 0.04）和IL-1受体拮抗剂（P < 0.001）持续下降。9名女性（60%）在使用DMPA后检测到卷曲乳杆菌，这与IL-6（P < 0.01）和IL-8（P = 0.02）的降低显著相关。
结论
开始使用DMPA导致阴道细菌浓度和炎症介质水平持续变化。有必要进一步研究以明确受DMPA使用影响的阴道微生物群成分及其对HIV易感性的影响。
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