DMPA use does not increase HIV risk by increasing bacterial vaginosis or vaginal candidiasis. COC use may predispose for vaginal candidiasis, but is not believed to be associated with increased HIV acquisition. However, the potential role of Candida species, and vaginal microbiome imbalances other than bacterial vaginosis or Candida species, in HIV transmission cannot yet be ruled out. Further in-depth molecular studies are needed.

Oral contraceptive and injectable use were associated with several STIs but not with VMB composition. The increased herpes simplex virus-2 prevalence among injectable users might explain the potentially higher HIV risk in these women, but more research is needed to confirm these results and elucidate biological mechanisms.

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BACKGROUND: Metronidazole is the first-line treatment for bacterial vaginosis, but cure rates are suboptimal and recurrence rates high. OBJECTIVES: To evaluate the impact of a standard course of oral metronidazole treatment (500 mg twice per day for 7 days) on the vaginal microbiota of Rwandan bacterial vaginosis patients using microscopy and 16S rRNA gene sequencing, and to evaluate correlates of treatment failure. STUDY DESIGN: HIV-negative, nonpregnant women aged 18e45 years with bacterial vaginosis and/or Trichomonas vaginalis (N¼68) were interviewed and sampled before and after metronidazole treatment. They were also screened, and treated if applicable, for other urogenital infections. The vaginal microbiota was assessed by Gram stain Nugent scoring, Illumina 16S rRNA HiSeq sequencing (relative abundances), and BactQuant 16S gene quantitative polymerase chain reaction (estimated concentrations). Only women with a pretreatment Nugent score of 7e10 and a valid posttreatment Nugent score (N¼55) were included in metronidazole treatment failure analyses, with treatment failure defined as a posttreatment Nugent score of 4e10. RESULTS: The bacterial vaginosis cure rate by Nugent scoring was 54.5%. The mean total vaginal bacterial concentration declined from 6.59 to 5.85 log 10 /mL (P<.001), which was mostly due to a reduction in mean bacterial vaginosis-associated anaerobes concentration (all bacterial vaginosis-associated anaerobe taxa combined) from 6.23 to 4.55 log 10 / mL (P<.001). However, only 16.4% of women had a bacterial vaginosis anaerobes concentration reduction of more than 50%, and only 3 women had complete eradication. The mean concentration of lactobacilli (all species combined) increased from 4.98 to 5.56 log 10 /mL (P¼.017), with L. iners being the most common species pre-and posttreatment. The mean concentration of pathobionts (defined as Proteobacteria, streptococci, staphylococci, enterococci, and a few others) did not change significantly: from 1.92 log 10 /mL pretreatment to 2.01 log 10 /mL posttreatment (P¼.939). Pretreatment pathobionts concentration, and having a pretreatment vaginal microbiota type containing more than 50% Gardnerella vaginalis (compared with less than 50%), were associated with increased likelihood of treatment failure, but the latter did not reach statistical significance (P¼.044 and P¼.084, respectively). CONCLUSIONS: Metronidazole alone may not cure women with high G. vaginalis relative abundance, potentially due to biofilm presence, and women with high pathobionts concentration. These women may benefit from additional biofilm-disrupting and/or pathobiont-targeting treatments.

Background Vaginal probiotics claiming to cure and/or prevent bacterial and/or fungal vaginal dysbiosis are available on the market but, until recently, did not have to be approved as drugs for human use. Objectives We evaluated the impact of vaginal probiotics on bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC) cure and/or recurrence, as well as vaginal microbiota (VMB) composition and vaginal detection of probiotic strains. Search strategy We performed a systematic literature search in MEDLINE and Embase up to 15 January 2019. Selection criteria There were no restrictions in probiotic strains/formulations, study populations, and designs. BV had to be diagnosed by Nugent or Ison‐Hay Gram stain scoring, VVC by culture, wet mount or PCR, and VMB composition/detection by molecular techniques. Data collection and analysis The authors independently extracted data. Main results All 22 vaginal probiotics evaluated in the 34 eligible studies contained Lactobacillus strains, and some contained additional active ingredients. The probiotics hold promise for BV cure and prevention, but much less so for VVC cure and prevention. No major safety concerns were reported in any of the studies. Vaginal detection of probiotic strains never lasted long beyond the dosing period, suggesting that they did not colonise the vagina. However, findings are not definitive because heterogeneity was high and the quality of most studies suboptimal. Conclusions Availability of vaginal probiotics for vaginal health indications will likely decline in 2020 because of regulatory changes. We urge the field to invest in clinical evidence‐based product development and to conduct future trials more rigorously. Tweetable abstract Lactobacilli‐containing vaginal probiotics hold promise for bacterial vaginosis cure and prevention, but not for vulvovaginal candidiasis.

Having pathobionts was positively associated with young age, non-Dutch origin, hormonal contraceptive use, smoking, antibiotic use in the 14 days prior to sampling, van de Wijgert et al. Pathobionts in the Vaginal MicrobiotaHIV status, and the presence of sexually transmitted pathogens, in at least one but not all studies; inconsistently associated with sexual risk-taking and unusual vaginal discharge reporting; and not associated with vaginal yeasts detection by microscopy. We recommend that future VMB studies quantify common vaginal pathobiont genera.

Bacterial vaginosis (BV) is associated with HIV acquisition and adverse pregnancy outcomes. Recurrence after metronidazole treatment is high. HIV-negative, non-pregnant Rwandan BV patients were randomized to four groups (n = 17/group) after seven-day oral metronidazole treatment: behavioral counseling only (control), or counseling plus intermittent use of oral metronidazole, Ecologic Femi+ vaginal capsule (containing multiple Lactobacillus and one Bifidobacterium species), or Gynophilus LP vaginal tablet (L. rhamnosus 35) for two months. Vaginal microbiota assessments at all visits included Gram stain Nugent scoring and 16S rRNA gene qPCR and HiSeq sequencing. All interventions were safe. BV (Nugent 7-10) incidence was 10.18 per person-year at risk in the control group, and lower in the metronidazole (1.41/person-year; p = 0.004), Ecologic Femi+ (3.58/person-year; p = 0.043), and Gynophilus LP groups (5.36/person-year; p = 0.220). In mixed effects models adjusted for hormonal contraception/pregnancy, sexual risk-taking, and age, metronidazole and Ecologic Femi+ users, each compared to controls, had higher Lactobacillus and lower BV-anaerobes estimated concentrations and/ or relative abundances, and were less likely to have a dysbiotic vaginal microbiota type by sequencing. Inter-individual variability was high and effects disappeared soon after intervention cessation. Lactobacilli-based vaginal probiotics warrant further evaluation because, in contrast to antibiotics, they are not expected to negatively affect gut microbiota or cause antimicrobial resistance.Most women have a vaginal microbiota (VMB) that consists predominantly of lactobacilli 1 . The most common type of vaginal dysbiosis is bacterial vaginosis (BV), characterized by a decrease in lactobacilli and increase in fastidious anaerobes 2 . Other types of bacterial dysbiosis, vulvovaginal candidiasis, and Trichomonas vaginalis (TV) are also common. These conditions are associated with vaginal inflammation, thereby increasing the risk of HIV acquisition 3 . BV is also associated with pelvic inflammatory disease, infertility, and adverse pregnancy outcomes 2 .The majority of women seeking care for vaginal symptoms receive antibiotic or antifungal treatment empirically or syndromically without any diagnostic testing 4 . In some specialized clinics, women might be offered www.nature.com/scientificreports www.nature.com/scientificreports/ limited diagnostic testing, such as vaginal pH determination and/or wet mount microscopy. In research settings, BV is typically diagnosed by the Amsel criteria or Nugent scoring 5,6 , with the latter currently being considered the gold standard: Gram-stained vaginal smears are scored based on microscopic visualization of three bacterial morphotypes with a score of 0-3 considered normal, 4-6 intermediate, and 7-10 BV regardless of symptoms. In the last 15 years, molecular methods have become more widely available, and have been applied to the VMB, although mostly in descriptive studies to date 1 .Evidence is mounting that 'm...

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