Cervical Secretions from Women After Depot Medroxyprogesterone Acetate (Depo-Provera) Administration Promote HIV Infectivity Ex Vivo.

IF 3.5 3区 医学 Q2 VIROLOGY
Viruses-Basel Pub Date : 2025-09-22 DOI:10.3390/v17091283
Carley Tasker, Natalie E Roche, Yungtai Lo, Theresa L Chang
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Abstract

Depot medroxyprogesterone acetate (Depo-Provera) has been associated with an increased risk of HIV acquisition. We have previously shown that Depo-Provera administration increases immune markers for HIV preference on peripheral and cervical CD4+ T cells but decreases the levels of most immune mediators at vaginal and cervical mucosa. In this study, we determined the effect of cervicovaginal secretions from women before (visit 1), one month (visit 2) and three months (visit 3) after Depo-Provera treatment on HIV infectivity ex vivo. The effect of supernatants from vaginal, endocervical, and rectal swabs and from cervical cytobrush on HIV infectivity were assessed by a single-cycle infection assay using CCR5-using HIV-luciferase reporter viruses. We found that endocervical secretions from women after Depo-Provera treatment promoted HIV infectivity. When analyzing the association between endocervical mediator changes in response to Depo-Provera, available in our previous study, and the changes in HIV infectivity pre- and post-treatment, we found that changes in IL-17 and VEGF were positively associated with changes in HIV infectivity at visit 2 compared with visit 1, whereas changes in RANTES and IL-4 were negatively associated with HIV infectivity. The negative association between RANTES and HIV infectivity was also observed at visit 3 compared with visit 1. Additionally, changes in IL-1α at visit 3 were positively associated with changes in HIV infectivity compared with visit 1. These findings suggest that Depo-Provera may increase the HIV risk by shifting the mucosal milieu that promotes HIV infectivity.

Abstract Image

服用醋酸甲孕酮后妇女宫颈分泌物促进体外HIV感染。
Depot羟孕酮醋酸酯(Depo-Provera)与艾滋病毒感染风险增加有关。我们之前的研究表明,Depo-Provera给药增加了外周和宫颈CD4+ T细胞上HIV偏好的免疫标记物,但降低了阴道和宫颈粘膜上大多数免疫介质的水平。在这项研究中,我们确定了妇女在Depo-Provera治疗前(访问1)、1个月(访问2)和3个月(访问3)后宫颈阴道分泌物对体外HIV感染的影响。使用ccr5 -使用HIV荧光素酶报告病毒进行单周期感染试验,评估阴道、宫颈、直肠拭子和宫颈细胞刷上清液对HIV感染的影响。我们发现经Depo-Provera治疗的妇女宫颈内分泌物促进了HIV感染。在我们之前的研究中,我们分析了Depo-Provera治疗后宫颈内介质的变化与治疗前后HIV传染性的变化之间的关系,我们发现IL-17和VEGF的变化与第2次访问时HIV传染性的变化呈正相关,而RANTES和IL-4的变化与HIV传染性呈负相关。与第一次访问相比,第3次访问时也观察到RANTES与HIV感染之间的负相关。此外,与第一次访问相比,第3次访问时IL-1α的变化与HIV传染性的变化呈正相关。这些发现表明,Depo-Provera可能通过改变促进HIV感染的粘膜环境来增加HIV风险。
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来源期刊
Viruses-Basel
Viruses-Basel VIROLOGY-
CiteScore
7.30
自引率
12.80%
发文量
2445
审稿时长
1 months
期刊介绍: Viruses (ISSN 1999-4915) is an open access journal which provides an advanced forum for studies of viruses. It publishes reviews, regular research papers, communications, conference reports and short notes. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced. We also encourage the publication of timely reviews and commentaries on topics of interest to the virology community and feature highlights from the virology literature in the ''News and Views'' section. Electronic files or software regarding the full details of the calculation and experimental procedure, if unable to be published in a normal way, can be deposited as supplementary material.
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