Can norethisterone enantate (NET-EN) reduce the risk of recurrent bacterial vaginosis in women at high risk for HIV infection?

庚酸炔诺酮 (NET-EN) 能否降低 HIV 感染高危女性复发细菌性阴道病的风险？

• 批准号: MR/N023692/1
• 负责人: Suzanna Francis
• 金额: $ 102.46万
• 依托单位: London School of Hygiene & Tropical Medicine
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FN023692%2F1
• 关键词: norethisterone; enantate; NET; EN; reduce

Bacterial vaginosis is a common condition in which the balance of bacteria inside the vagina becomes disrupted. Bacterial vaginosis can cause an abnormal discharge and unpleasant odour, and it is one of the most common reasons women seek reproductive health care, although many women have no symptoms. We do not understand the causes of bacterial vaginosis or how to control it long-term. Importantly, it is a risk factor for premature births, pelvic inflammatory disease, and sexually transmitted infections, including HIV. This is of particular concern among women at high risk for HIV infection where bacterial vaginosis is also highly prevalent. In a study among female sex workers in Kampala, Uganda, we found that 56% of the women had bacterial vaginosis, and after treatment, 72% of these women tested positive again within 3 months. Developing more robust treatment for bacterial vaginosis is important for HIV prevention in key populations at increased risk for HIV infection.Several types of hormonal contraceptives have been shown to decrease a woman's risk of bacterial vaginosis, including an injectable progestin-only contraceptive called depot medroxyprogesterone acetate (DMPA). However, the use of DMPA to prevent bacterial vaginosis is problematic because there is evidence that DMPA also increases the risk of HIV infection. Thus, there is a paradox: both bacterial vaginosis and DMPA are risk factors for HIV infection, yet DMPA is protective against recurrent bacterial vaginosis. DMPA is the most popular form of hormonal contraceptive in East and Southern Africa. However, there is growing evidence that newer forms of progestin-only injectable contraceptives, such as norethisterone enantate (NET-EN) do not have a harmful effect on HIV risk. Newer contraceptives such as NET-EN may serve a dual purpose of preventing recurrent bacterial vaginosis and increasing options for safe, acceptable and reliable hormonal contraception among women at high risk for HIV. To date, no published studies have investigated the effect of NET-EN on vaginal bacteria. Safe and effective hormonal contraception may augment current or future treatment for women with recurrent bacterial vaginosis, but we need to know more about the effects of non-DMPA hormonal contraception on the vaginal bacteria and reproductive tract. We work with a cohort of female sex workers in Kampala, Uganda. Approximately one quarter of women in this cohort use DMPA, and no women use NET-EN even though it is available from the clinic. We plan to carry out a study to investigate the effects of NET-EN and DMPA on a wide range of outcomes, including vaginal bacteria, in this cohort. We will invite women who are HIV negative and bacterial vaginosis positive to join our study. All women will be treated for bacterial vaginosis. Consenting women who are not currently using a type of reliable contraceptive will be allocated at random to receive either NET-EN plus condoms or condoms only. Consenting women already using DMPA will also be enrolled. Both groups will be followed 7 months to see the effects on the vaginal bacteria and reproductive tract. We will also interview women who have started NET-EN as a part of this study to find out their opinion about using NET-EN. Outcomes from this study will provide information for future treatment trials for both bacterial vaginosis and HIV prevention.

细菌性阴道病是一种常见的情况，在这种情况下，阴道内的细菌平衡被破坏。细菌性阴道病会导致异常分泌物和难闻的气味，这是女性寻求生殖健康护理的最常见原因之一，尽管许多女性没有症状。我们不了解细菌性阴道病的原因，也不知道如何长期控制它。重要的是，它是早产、盆腔炎和包括艾滋病毒在内的性传播感染的危险因素。这在感染艾滋病毒的高危妇女中尤其令人担忧，因为细菌性阴道病也非常普遍。在乌干达坎帕拉的一项对女性性工作者的研究中，我们发现56%的女性患有细菌性阴道病，经过治疗后，这些女性中有72%的人在3个月内再次检测呈阳性。开发更有效的治疗细菌性阴道病的方法对于在艾滋病毒感染风险增加的关键人群中预防艾滋病毒非常重要。已有证据表明，几种类型的激素避孕药可以降低妇女患细菌性阴道病的风险，其中包括一种仅含孕激素的可注射避孕药，名为醋酸甲羟孕酮(DMPA)。然而，使用DMPA预防细菌性阴道病是有问题的，因为有证据表明，DMPA也会增加感染艾滋病毒的风险。因此，出现了一个悖论：细菌性阴道病和DMPA都是艾滋病毒感染的危险因素，但DMPA对复发的细菌性阴道病具有保护作用。DMPA是东非和南部非洲最受欢迎的荷尔蒙避孕药。然而，越来越多的证据表明，新形式的仅含孕激素的可注射避孕药，如炔诺酮(NET-EN)对艾滋病毒风险没有有害影响。新型避孕药，如Net-en，可能具有双重作用，既要防止细菌性阴道病复发，又要在感染艾滋病毒的高危妇女中增加安全、可接受和可靠的激素避孕选择。到目前为止，还没有公开发表的研究调查Net-en对阴道细菌的影响。安全有效的激素避孕可能会增加目前或未来对复发性细菌性阴道病的治疗，但我们需要更多地了解非DMPA激素避孕对阴道细菌和生殖道的影响。我们和乌干达坎帕拉的一群女性性工作者一起工作。在这个队列中，大约四分之一的女性使用DMPA，没有女性使用Net-EN，即使它可以从诊所获得。我们计划在这个队列中开展一项研究，调查Net-EN和DMPA对包括阴道细菌在内的广泛结果的影响。我们将邀请HIV阴性、细菌性阴道病阳性的女性加入我们的研究。所有女性都将接受细菌性阴道病的治疗。同意目前没有使用可靠避孕药的妇女将被随机分配到Net-EN plus避孕套或仅获得避孕套。已经使用DMPA的同意女性也将被登记。两组均随访7个月，观察对阴道细菌和生殖道的影响。作为这项研究的一部分，我们还将采访已经开始使用Net-en的女性，以了解她们对使用Net-en的看法。这项研究的结果将为未来细菌性阴道病和艾滋病毒预防的治疗试验提供信息。

项目成果

The Presence of Hemoglobin in Cervicovaginal Lavage Is Not Associated With Genital Schistosomiasis in Zambian Women From the BILHIV Study.

• DOI: 10.1093/ofid/ofac586
• 发表时间: 2022-12
• 期刊: Open forum infectious diseases
• 影响因子: 4.2

Working from home and intimate partner violence among cis-women during the COVID-19 pandemic: evidence from a global, cross-sectional study.

• DOI: 10.1186/s12889-023-15785-7
• 发表时间: 2023-05-26
• 期刊: BMC public health
• 影响因子: 4.5

Additional file 1: of Reported oral and anal sex among adolescents and adults reporting heterosexual sex in sub-Saharan Africa: a systematic review

附加文件 1：撒哈拉以南非洲地区报告异性性行为的青少年和成人口交和肛交的报告：系统评价

• DOI: 10.6084/m9.figshare.8087822
• 发表时间: 2019
• 作者: Morhason-Bello I

Female Genital Schistosomiasis and HIV-1 Incidence in Zambian Women: A Retrospective Cohort Study.

• DOI: 10.1093/ofid/ofab349
• 发表时间: 2021-07
• 期刊: Open forum infectious diseases
• 影响因子: 4.2
• 作者: Sturt AS;Webb EL;Phiri CR;Mudenda M;Mapani J;Kosloff B;Cheeba M;Shanaube K;Bwalya J;Kjetland EF;Francis SC;Corstjens PLAM;van Dam GJ;van Lieshout L;Hansingo I;Ayles H;Hayes RJ;Bustinduy AL
• 通讯作者: Bustinduy AL

Association of Female Genital Schistosomiasis With the Cervicovaginal Microbiota and Sexually Transmitted Infections in Zambian Women.

• DOI: 10.1093/ofid/ofab438
• 发表时间: 2021-09
• 期刊: Open forum infectious diseases
• 影响因子: 4.2
• 作者: Sturt AS;Webb EL;Himschoot L;Phiri CR;Mapani J;Mudenda M;Kjetland EF;Mweene T;Levecke B;van Dam GJ;Corstjens PLAM;Ayles H;Hayes RJ;van Lieshout L;Hansingo I;Francis SC;Cools P;Bustinduy AL
• 通讯作者: Bustinduy AL