Can norethisterone enantate (NET-EN) reduce the risk of recurrent bacterial vaginosis in women at high risk for HIV infection? 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. The Global Challenges Research Fund (GCRF) supports cutting-edge research to address challenges faced by developing countries. The fund addresses the UN sustainable development goals. It aims to maximise the impact of research and innovation to improve lives and opportunity in the developing world.