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

细菌性阴道病是一种常见的疾病，其中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，这是妇女寻求生殖保健的最常见原因之一，尽管许多妇女没有症状。我们不了解细菌性阴道病的原因或如何长期控制它。重要的是，它是早产、盆腔炎和性传播感染（包括艾滋病毒）的风险因素。这在感染艾滋病毒风险高的妇女中尤其令人关切，因为细菌性阴道病也非常普遍。在乌干达坎帕拉的一项女性性工作者研究中，我们发现56%的女性患有细菌性阴道病，治疗后，72%的女性在3个月内再次检测呈阳性。开发更有效的细菌性阴道病治疗方法对于HIV感染风险增加的关键人群的HIV预防非常重要。几种类型的激素避孕药已被证明可以降低女性患细菌性阴道病的风险，包括一种名为长效醋酸甲羟孕酮（DMPA）的注射型仅含孕激素的避孕药。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HIV感染的风险。因此，存在一个悖论：细菌性阴道病和DMPA都是HIV感染的危险因素，但DMPA对复发性细菌性阴道病有保护作用。DMPA是东非和南部非洲最流行的激素避孕药。然而，越来越多的证据表明，新形式的仅含孕激素的注射避孕药，如炔诺酮庚酸酯（NET-EN）对艾滋病毒风险没有有害影响。NET-EN等较新的避孕药可能具有双重目的，即预防复发性细菌性阴道病，并增加艾滋病毒高危妇女安全、可接受和可靠的激素避孕选择。到目前为止，还没有发表的研究调查了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妇女的治疗，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。我们在乌干达的坎帕拉与一群女性性工作者一起工作。该队列中约有四分之一的妇女使用DMPA，没有妇女使用NET-EN，即使它可以从诊所获得。我们计划进行一项研究，以调查NET-EN和DMPA对该队列中包括阴道细菌在内的广泛结局的影响。我们将邀请HIV阴性和细菌性阴道病阳性的女性参加我们的研究。所有妇女都将接受细菌性阴道病治疗。目前没有使用某种可靠避孕药具的妇女将被随机分配接受NET-EN加避孕套或只接受避孕套。已经使用DMPA的女性也将入组。两组都将随访7个月，以观察对阴道细菌和生殖道的影响。我们还将采访已经开始使用NET-EN的妇女，作为这项研究的一部分，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。

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.