Transkingdom Analysis of the Female Reproductive Tract Reveals Bacteriophages form Communities.

The female reproductive tract (FRT) microbiome plays a vital role in maintaining vaginal health. Viruses are key regulators of other microbial ecosystems, but little is known about how the FRT viruses (virome), particularly bacteriophages that comprise the phageome, impact FRT health and dysbiosis. We hypothesize that bacterial vaginosis (BV) is associated with altered FRT phageome diversity, transkingdom interplay, and bacteriophage discriminate taxa. Here, we conducted a retrospective, longitudinal analysis of vaginal swabs collected from 54 BV-positive and 46 BV-negative South African women. Bacteriome analysis revealed samples clustered into five distinct bacterial community groups (CGs), and further, bacterial alpha diversity was significantly associated with BV. Virome analysis on a subset of baseline samples showed FRT bacteriophages clustering into novel viral state types (VSTs), a viral community clustering system based on virome composition and abundance. Distinct BV bacteriophage signatures included increased alpha diversity along with discriminant Bacillus, Burkholderia, and Escherichia bacteriophages. Bacteriophage-bacteria transkingdom associations were also identified between Bacillus and Burkholderia viruses and BV-associated bacteria, providing key insights for future studies elucidating the transkingdom interactions driving BV-associated microbiome perturbations. In this cohort, bacteriophage-bacterial associations suggest complex interactions, which may play a role in the establishment and maintenance of BV.

Analysis of HPV Genotypes and Liquid-Based Cervical Cytology: Results from a Tertiary Academic Center in Northwestern Turkey.

High-risk human papilloma virus (hrHPV) plays an important role in cervical cancer. The aim of this study was to investigate the distribution of HPV genotypes in the region and to correlate it with liquid-based-cytology (LBC) and colposcopic biopsy results. Furthermore, the potential relationship between HPV infections and bacterial vaginosis (BV) was investigated. HPV genotypes were determined using real-time PCR. LBC, biopsies, and BV examinations were performed by the Pathology and Cytology. Consecutive cervical specimens of 409 women who underwent both cytology and HPV-DNA tests were included in the study. A total of 172 (42.1%) patients were positive for HPV-DNA; of these, 107 (26.2%) had hrHPV. The most common HPV genotypes were HPV 59, 16, 33, 52, and 51, at 16.6%, 15.9%, 13.4%, 13.4%, and 8.9%, respectively. Epithelial cell abnormality was detected in 11.5% of LBC test results. The genotypes of HPV 33, 56, 66, and 68 were found at a higher rate in patients with epithelial cell abnormalities than in those with no detected abnormalities. Bacterial vaginosis was found in 24 patients (5.9%). HPV-DNA positivity was observed to be statistically higher in patients with BV than in those without BV.

The impact of cervical cytobrush sampling on cervico-vaginal immune parameters and microbiota relevant to HIV susceptibility.

The immunology and microbiota of the female genital tract (FGT) are key determinants of HIV susceptibility. Cervical cytobrush sampling is a relatively non-invasive method permitting the longitudinal assessment of endocervical immune cells, but effects on FGT immunology are unknown. Blood, cervico-vaginal secretions and cervical cytobrushes were collected from sexually transmitted infection (STI)-free women at baseline and after either 6 hours or 48 hours. Endocervical immune cell subsets were assessed by flow cytometry, and pro-inflammatory cytokines by multiplex ELISA. The density of Lactobacillus species and key bacterial vaginosis-associated bacterial taxa were determined by qPCR. Paired changes were assessed before and after cytobrush sampling. After 6 hours there were significant increases in CD4 + T cell, antigen presenting cell (APC) and neutrophil numbers; APC elevations persisted at 48 hours, while neutrophil and CD4 + T cell numbers returned to baseline. In addition, pro-inflammatory cytokine levels were increased at 6 hours and returned to baseline by 48 hours. No significant changes were observed in the absolute abundance of Lactobacillus species or BV-associated bacteria at either time point. Overall, cytobrush sampling altered genital immune parameters at 6 hours, but only APC number increases persisted at 48 hours. This should be considered in longitudinal analyses of FGT immunology.

Hormonal Contraception and Vaginal Infections Among Couples Who Are Human Immunodeficiency Virus Serodiscordant in Lusaka, Zambia.

OBJECTIVE: To examine the relationship between hormonal contraception and vaginal infections with bacterial vaginosis, vaginal candidiasis, or trichomoniasis. METHODS: Couples who were human immunodeficiency virus (HIV) serodiscordant in Zambia were enrolled in a longitudinal cohort study. From 1994 to 2002, both partners were seen quarterly and received physical exams including genital examinations. Separate rates for three outcome infections of interest (bacterial vaginosis, vaginal candidiasis, and trichomoniasis) were calculated. Bivariate associations between baseline and time-varying covariates and outcome infections of interest were evaluated using unadjusted Anderson-Gill survival models. Adjusted hazard ratios (aHRs) were generated using multivariable Anderson-Gill survival models that included demographic and clinical factors associated with both hormonal contraceptive use and each infection of interest. RESULTS: There were 1,558 cases of bacterial vaginosis, 1,529 cases of vaginal candidiasis, and 574 cases of trichomoniasis over 2,143 person-years of observation. Depot medroxyprogesterone acetate (DMPA) users had significantly lower rates of trichomoniasis and bacterial vaginosis. In adjusted models, DMPA was protective for bacterial vaginosis (aHR=0.72; 95% CI 0.54-0.95), candidiasis (aHR 0.75, 95% CI 0.57-1.00) and trichomoniasis (aHR=0.43, 95% CI 0.25-0.74). Oral contraceptive pills were protective for candidiasis (aHR=0.79, 95% CI 0.65-0.97). CONCLUSION: We confirm that DMPA use was associated with reduced rates of the three most common causes of vaginitis, and oral contraceptive pill use was associated with reduced rates of candidiasis among women in couples who were HIV discordant.

Long-term Lactobacillus rhamnosus BMX 54 application to restore a balanced vaginal ecosystem: a promising solution against HPV-infection.

BACKGROUND: Over recent years, a growing interest has developed in microbiota and in the concept of maintaining a special balance between Lactobacillus and other bacteria species in order to promote women's well-being. The aim of our study was to confirm that vaginal Lactobacilli long-lasting implementation in women with HPV-infections and concomitant bacterial vaginosis or vaginitis might be able to help in solving the viral infection, by re-establishing the original eubiosis. METHODS: A total of 117 women affected by bacterial vaginosis or vaginitis with concomitant HPV-infections were enrolled at Department of Gynecological Obstetrics and Urological Sciences, La Sapienza University, Rome, Italy between February 2015 and March 2016. Women were randomized in two groups, standard treatment (metronidazole 500 mg twice a day for 7 days or fluconazole 150 mg orally once a day for 2 consecutive days) plus short-term (3 months) vaginal Lactobacillus implementation (group 1, short probiotics treatment protocol group, n = 60) versus the same standard treatment plus long-lasting (6 months) vaginal Lactobacillus rhamnosus BMX 54 administration (group 2, treatment group, n = 57). RESULTS: After a median follow up of 14 months (range 9-30 months) the chance to solve HPV-related cytological anomalies was twice higher in probiotic long-term users (group 2) versus short probiotics implementation group (group 1) (79.4% vs 37.5%, p = 0.041). Moreover, a total HPV-clearance was shown in 11.6% of short schedule probiotics implementation patients compared to a percentage of 31.2% in vaginal Lactobacilli long term users (p = 0.044), assessed as negative HPV-DNA test documented at the end of the study period. CONCLUSIONS: The consistent percentage of clearance of PAP-smear abnormalities and HPV-clearance obtained in long-term treatment group has been interestingly high and encouraging. Obviously, larger and randomized studies are warranted to confirm these encouraging results, but we believe that eubiosis re-establishment is the key to tackle effectively even HPV-infection. TRIAL REGISTRATION: Retrospectively registered on PRS NCT03372395 (12/12/2017).

Bacterial vaginosis, human papilloma virus and herpes viridae do not predict vaginal HIV RNA shedding in women living with HIV in Denmark.

BACKGROUND: Bacterial vaginosis (BV) has been found to be associated with HIV acquisition and transmission. This is suggested to be due to higher HIV RNA levels in cervicovaginal fluids in women living with HIV (WLWH) with BV, as bacteria associated with BV may induce viral replication and shedding in the genital tract despite undetectable HIV RNA plasma viral load. We examined the prevalence and diagnostic predictors of BV and HIV-1 RNA vaginal shedding in women living with HIV (WLWH) in Denmark, taking into account the presence of human papillomavirus (HPV) and herpes viridae. METHODS: WLWH between 18-51 years were recruited from six Departments of Infectious Diseases in Denmark during enrolment in the SHADE cohort; a prospective cohort study of WLWH attending regular outpatient care. BV was diagnosed by microscopy of vaginal swabs and PCR was used for detection of BV-associated bacteria, HPV, herpes viridae, and vaginal HIV viral load. RESULTS: Median age of the 150 included women was 41 years; ethnicity was predominantly White (35%) or Black (47%). The majority (96%) was on ART and had undetectable (85%) plasma HIV RNA (<40 copies/mL). BV was diagnosed in 32%. Overall, 11% had detectable vaginal HIV RNA. Both before and after adjustment for BV, age, ethnicity, plasma HIV RNA, CD4 cell count, herpes viridae and HPV, we found no significant predictors of HIV RNA vaginal shedding. CONCLUSION: In well-treated WLWH, BV, herpes viridae or HPV do not predict vaginal HIV RNA shedding. This implies that HIV shedding does not seem to be increased by BV.

The Cervicovaginal Microbiota and Its Associations With Human Papillomavirus Detection in HIV-Infected and HIV-Uninfected Women.

BACKGROUND: Bacterial vaginosis (BV) is characterized by low abundance of Lactobacillus species, high pH, and immune cell infiltration and has been associated with an increased risk of human papillomavirus (HPV) infection. We molecularly assessed the cervicovaginal microbiota over time in human immunodeficiency virus (HIV)-infected and HIV-uninfected women to more comprehensively study the HPV-microbiota relationship, controlling for immune status. METHODS: 16S ribosomal RNA gene amplicon pyrosequencing and HPV DNA testing were conducted annually in serial cervicovaginal lavage specimens obtained over 8-10 years from African American women from Chicago, of whom 22 were HIV uninfected, 22 were HIV infected with a stable CD4+ T-cell count of > 500 cells/mm3, and 20 were HIV infected with progressive immunosuppression. Vaginal pH was serially measured. RESULTS: The relative abundances of Lactobacillus crispatus and other Lactobacillus species were inversely associated with vaginal pH (all P < .001). High (vs low) L. crispatus relative abundance was associated with decreased HPV detection (odds ratio, 0.48; 95% confidence interval, .24-.96; Ptrend = .03) after adjustment for repeated observation and multiple covariates, including pH and study group. However, there were no associations between HPV and the relative abundance of Lactobacillus species as a group, nor with Lactobacillus gasseri, Lactobacillus iners, and Lactobacillus jensenii individually. CONCLUSIONS: L. crispatus may have a beneficial effect on the burden of HPV in both HIV-infected and HIV-uninfected women (independent of pH).

Longitudinal Assessment of Systemic and Genital Tract Inflammatory Markers and Endogenous Genital Tract E. coli Inhibitory Activity in HIV-Infected and Uninfected Women.

PROBLEM: Stability over time of systemic and mucosal immunity and their associations with bacterial vaginosis (BV) and HIV-specific parameters were assessed. METHOD OF STUDY: Immune mediators and HIV viral load in plasma and cervicovaginal lavage (CVL), E. coli inhibition, and Nugent score were measured at three semiannual visits among 94 participants in the Women's Interagency HIV Study. Mixed models identified the factors associated with immune mediators. RESULTS: There was higher E. coli inhibition and lower inflammation over time in the genital tract and systemically. BV was consistently associated with higher CVL inflammatory mediators and lower CVL E. coli inhibition. HIV-infected women with higher CD4 counts had lower systemic and genital inflammatory mediators, and genital HIV shedding was associated with higher CVL inflammatory mediators. Use of antiretroviral therapy (ART) was associated with lower plasma and CVL mediators, but higher E. coli inhibition. CONCLUSION: HIV and BV are linked to inflammation, and ART may be associated with improved vaginal health.

Chlamydial Pre-Infection Protects from Subsequent Herpes Simplex Virus-2 Challenge in a Murine Vaginal Super-Infection Model.

Chlamydia trachomatis and Herpes Simplex Virus-2 (HSV-2) genital tract co-infections have been reported in humans and studied in vitro but the clinical consequences are unknown. Limited epidemiologic evidence suggests that these co-infections could be more severe than single infections of either pathogen, but the host-pathogen interactions during co-infection remain uncharacterized. To determine whether disease progression and/or pathogen shedding differs between singly-infected and super-infected animals, we developed an in vivo super-infection model in which female BALB/c mice were vaginally infected with Chlamydia muridarum (Cm) followed later by HSV-2. Pre-infection with Chlamydia 3 or 9 days prior to HSV-2 super-infection conferred significant protection from HSV-2-induced neurologic disease and significantly reduced viral recovery compared to HSV-2 singly-infected controls. Neither protection from mortality nor reduced viral recovery were observed when mice were i) super-infected with HSV-2 on day 27 post Cm; ii) infected with UV-irradiated Cm and super-infected with HSV-2; or iii) azithromycin-treated prior to HSV-2 super-infection. Therefore, protection from HSV-2-induced disease requires active infection with viable chlamydiae and is not observed after chlamydial shedding ceases, either naturally or due to antibiotic treatment. Thus, Chlamydia-induced protection is transient and requires the continued presence of chlamydiae or their components. These data demonstrate that chlamydial pre-infection can alter progression of subsequent HSV-2 infection, with implications for HSV-2 transmission from co-infected humans.

A cross-sectional study of bacterial vaginosis, intravaginal practices and HIV genital shedding; implications for HIV transmission and women's health.

OBJECTIVES: Bacterial vaginosis (BV) is associated with an increased risk of HIV transmission, and intravaginal practices (IVP) are an important risk factor for developing BV. The relationship between IVP, BV and HIV lower genital shedding, responsible for HIV transmission, has not been examined in women receiving antiretrovirals in Zambia. DESIGN: Cross-sectional study. SETTING: Community Health Center in Lusaka, Zambia. PARTICIPANTS AND METHODS: Participants were HIV-infected women receiving antiretroviral therapy and engaging in IVP (n=128). Participants completed audio computer-administered self-interviews to assess IVP and underwent a vaginal examination. BV was diagnosed using Nugent criteria. HIV-1 lower genital shedding was assessed by measuring HIV-1 RNA in cervicovaginal lavages. RESULTS: Most women engaged in IVP daily (114, 89.0%) and 81 (63.3%) of the participants had BV. HIV-1 genital shedding was detected in 18 (14.2%) participants. BV was associated with daily use of IVP (prevalence ratio, PR=4.58, CI 1.26 to 16.64, p=0.02) and weekly use of traditional medicines for IVP (PR=1.33, CI 1.05 to 1.68, p=0.02). The only factor associated with HIV-1 lower genital shedding was plasma viraemia (PR=4.61, CI 2.02 to 10.54, p<0.001). Neither IVP nor BV were associated with HIV shedding. CONCLUSIONS: Despite the frequency of IVP and high prevalence of BV, plasma viraemia was the primary factor associated with HIV lower genital shedding. These findings support early initiation of antiretrovirals as an HIV prevention tool. Given adverse health outcomes associated with BV, the association between frequent IVP and BV, and the powerful local norms and traditions encouraging IVP, there is a need for studies assessing culturally tailored interventions to decrease BV in high-prevalence settings.

HIV-Enhancing Factors Are Secreted by Reproductive Epithelia upon Inoculation with Bacterial Vaginosis-Associated Bacteria.

Bacterial vaginosis is a common reproductive infection in which commensal vaginal lactobacilli are displaced by a mixed population of pathogenic bacteria. Bacterial vaginosis increases susceptibility to HIV, and it has been suggested that host innate immune responses to pathogenic bacteria contribute to enhanced infection, yet the cellular mechanisms mediating the increased HIV susceptibility remain uncharacterized. We evaluated the HIV-enhancing effects of bacterial vaginosis by inoculating endocervical epithelia with Atopobium vaginae, a bacterial vaginosis-associated bacteria, and assaying secreted factors for HIV-enhancing activity. When epithelia and A. vaginae were cocultured, we observed increased HIV-enhancing activity mediated by secreted low molecular weight factors. From this complex mixture we identified several upregulated host proteins, which functioned in combination to enhance HIV infection. These studies suggest that the host immune response to bacterial vaginosis-associated bacteria results in the release of HIV-enhancing factors. The combined activity of bacterial vaginosis-induced proteins likely mediates HIV enhancement.

Interplay between the temporal dynamics of the vaginal microbiota and human papillomavirus detection.

BACKGROUND: We sought to describe the temporal relationship between vaginal microbiota and human papillomavirus (HPV) detection. METHODS: Thirty-two reproductive-age women self-collected midvaginal swabs twice weekly for 16 weeks (937 samples). Vaginal bacterial communities were characterized by pyrosequencing of barcoded 16S rRNA genes and clustered into 6 community state types (CSTs). Each swab was tested for 37 HPV types. The effects of CSTs on the rate of transition between HPV-negative and HPV-positive states were assessed using continuous-time Markov models. RESULTS: Participants had an average of 29 samples, with HPV point prevalence between 58%-77%. CST was associated with changes in HPV status (P<.001). Lactobacillus gasseri-dominated CSTs had the fastest HPV remission rate, and a low Lactobacillus community with high proportions of the genera Atopobium (CST IV-B) had the slowest rate compared to L. crispatus-dominated CSTs (adjusted transition rate ratio [aTRR], 4.43, 95% confidence interval [CI], 1.11-17.7; aTRR, 0.33, 95% CI, .12-1.19, respectively). The rate ratio of incident HPV for low Lactobacillus CST IV-A was 1.86 (95% CI, .52-6.74). CONCLUSIONS: Vaginal microbiota dominated by L. gasseri was associated with increased clearance of detectable HPV. Frequent longitudinal sampling is necessary for evaluation of the association between HPV detection and dynamic microbiota.

Prevalence and predictors of cervicitis in female sex workers in Peru: an observational study.

BACKGROUND: Cervicitis is a syndrome of cervical inflammation and a common condition in female sex workers (FSW), a subpopulation vulnerable to sexually transmitted infections. Local data is essential for guiding syndromic management of cervicitis in FSW working in Peru. We sought to describe the prevalence and etiologies of cervicitis in this population. We also aimed to identify sociodemographic, behavioral and biological factors associated with cervicitis, including bacterial vaginosis (BV), a condition with a possible role in cervicitis. METHODS: FSW 18 years of age or older presenting to a free public sexual health clinic in Callao-Lima, Peru were eligible for inclusion upon consent. 467 participants completed a face-to-face questionnaire and underwent genital examination. Vaginal, endocervical and blood samples were collected and tested for C. trachomatis (CT), N. gonorrhea (GC), T. vaginalis (TV), BV, HIV and Human T-Cell Lymphotropic Virus -1. Logistic regression was used to determine whether sociodemographic, behavioral, or other sexual health related characteristics were associated with the diagnosis of cervicitis. RESULTS: Cervicitis was detected in 99 (24.9%) of 397 FSW. The presence of cervicitis was unable to be determined in 70 participants. In women with cervicitis, CT was present in 4.6% (4/87), TV in 4.0% (4/99), GC in 0% (0/87) and no pathogen was detected on cervical microbiology in 91.9% (91/99). BV was detected on vaginal microbiology in 36.9% (31/84) of cervicitis cases. BV was more common in women with cervicitis, however this association did not reach statistical significance (aOR = 1.47 [0.87, 2.48], p = 0.15). Other STI were not associated with cervicitis. Regular clinic attendance (aOR = 0.54 [0.34, 0.87], p = 0.01) and Ecuadorian nationality (aOR = 0.31 [0.13, 0.76], p = 0.01) were associated with reduced risk of cervicitis. CONCLUSIONS: Cervicitis was common in FSW working Peru and was predominantly nongonococcal and non-chlamydial in etiology. Further study is warranted to clarify the role of BV and other emerging cervicitis pathogens in this population. The current Peruvian program of free health checks for FSW may be effective for reducing rates of cervicitis. The protective effect of Ecuadorian nationality prompts further study.

Interaction between lactobacilli, bacterial vaginosis-associated bacteria, and HIV Type 1 RNA and DNA Genital shedding in U.S. and Kenyan women.

Bacterial vaginosis has been associated with genital HIV-1 shedding; however, the effect of specific vaginal bacterial species has not been assessed. We tested cervicovaginal lavage from HIV-1-seropositive women for common Lactobacillus species: L. crispatus, L. jensenii, and seven BV-associated species: BVAB1, BVAB2, BVAB3, Leptotrichia, Sneathia, Megasphaera, and Atopobium spp. using quantitative PCR. We used linear and Poisson regression to evaluate associations between vaginal bacteria and genital HIV-1 RNA and DNA. Specimens from 54 U.S. (310 visits) and 50 Kenyan women (137 visits) were evaluated. Controlling for plasma viral load, U.S. and Kenyan women had similar rates of HIV-1 RNA (19% of visits vs. 24%; IRR=0.95; 95% CI 0.61, 1.49) and DNA shedding (79% vs. 76%; IRR=0.90; 0.78, 1.05). At visits during antiretroviral therapy (ART), the likelihood of detection of HIV-1 RNA shedding was greater with BVAB3 (IRR=3.16; 95% CI 1.36, 7.32), Leptotrichia, or Sneathia (IRR=2.13; 1.02, 4.72), and less with L. jensenii (IRR=0.39; 0.18, 0.84). At visits without ART, only L. crispatus was associated with a lower likelihood of HIV-1 RNA detection (IRR=0.6; 0.40, 0.91). Vaginal Lactobacillus species were associated with lower risk of genital HIV-1 shedding, while the presence of certain BV-associated species may increase that risk.

Bacterial vaginosis is conducive to the persistence of HPV infection.

We investigated the effects of bacterial vaginosis (BV) on the outcomes of high-risk human papillomavirus infection (HR-HPV). BV was diagnosed on Papanicolaou-stained cytology slides of 707 HPV-positive patients. HR-HPV DNA expression was analysed using the Hybrid Capture II (HC-II) assay. Of the 707 HR-HPV-positive female patients, 298 (42.1%) exhibited clearance of HR-HPV. The remaining 409 patients had persistent HR-HPV infection. The persistent HR-HPV group and the clearing group had similar rates of BV at the beginning of the study. At the end of the study, the persistent HR-HPV group had a BV prevalence of 11.2% while the clearing group had a significant lower BV prevalence of 5.0%. A decreased clearance of HPV was found in women with current BV, compared with women without BV. Furthermore, the natural history of HPV was not affected by the HPV viral load or the BV prevalence at the beginning of the study (P > 0.05). Bacterial vaginosis appears conducive to the persistence of HPV infection.

Recalcitrance of bacterial vaginosis among herpes-simplex-virus-type-2-seropositive women.

AIM: The multifactorial etiology of bacterial vaginosis (BV) impedes development of effective treatment and prevention strategies. Herein, we evaluated the effects of herpes simplex virus type 2 (HSV-2), a suspected BV risk factor, on vaginal flora composition. MATERIALS AND METHODS: Correlations between HSV-2 infection and BV were prospectively explored among 12 HSV-2-seropositive women with asymptomatic BV who were asked to collect daily vaginal swab specimens for Gram stain analysis of vaginal flora and determination of HSV-2 shedding frequencies during the 1month before and after metronidazole therapy. RESULTS: Unlike prior longitudinal studies that reported rapid fluctuations in vaginal flora composition and frequent episodes of spontaneously resolving BV, we found that 99.4% (310/312) of vaginal smears collected before initiation of metronidazole were consistent with a diagnosis of BV. Effectiveness of metronidazole therapy was also much lower than previously reported in studies not restricting enrollment to HSV-2-seropositive women; we observed a BV recurrence rate of 89% in the first month after completion of therapy while the median time to this recurrence occurred only 14days after treatment. CONCLUSIONS: Our study demonstrates BV recalcitrance among HSV-2-infected women and provides additional evidence for a linkage between this chronic viral infection and abnormal vaginal flora. Additional work will be needed to define mechanisms responsible for this correlation and to determine if vaginal flora health of HSV-2-infected women is improved by medications that suppress HSV-2 shedding.

Bacterial vaginosis and the natural history of human papillomavirus.

OBJECTIVE: To evaluate associations between common vaginal infections and human papillomavirus (HPV). STUDY DESIGN: Data from up to 15 visits on 756 HIV-infected women and 380 high-risk HIV-uninfected women enrolled in the HIV Epidemiology Research Study (HERS) were evaluated for associations of bacterial vaginosis, trichomoniasis, and vaginal Candida colonization with prevalent HPV, incident HPV, and clearance of HPV in multivariate analysis. RESULTS: Bacterial vaginosis (BV) was associated with increased odds for prevalent (aOR = 1.14, 95% CI: 1.04, 1.26) and incident (aOR = 1.24, 95% CI: 1.04, 1.47) HPV and with delayed clearance of infection (aHR = 0.84, 95% CI: 0.72, 0.97). Whereas BV at the preceding or current visit was associated with incident HPV, in an alternate model for the outcome of incident BV, HPV at the current, but not preceding, visit was associated with incident BV. CONCLUSION: These findings underscore the importance of prevention and successful treatment of bacterial vaginosis.

Bacterial vaginosis as a risk factor for high-grade cervical lesions and cancer in HIV-seropositive women.

OBJECTIVE: To assess the effect of bacterial vaginosis (BV) on the risk of high-grade squamous intraepithelial lesions (HSIL) among HIV-seropositive women. METHODS: A hospital-based prospective cohort study of HIV-seropositive women was conducted in Johannesburg, South Africa from January 2005 to September 2009. Multivariate log-binomial and Poisson regressions were used to estimate prevalence and rate ratios, respectively. RESULTS: Among 1954 HIV-seropositive women, the baseline prevalence of HSIL was 17%. BV prevalence was high (54%) and showed no association with prevalence of HSIL (adjusted prevalence ratio, 1.12; 95% confidence intervals (CI), 0.92-1.35) nor with cervical lesion progression at follow-up visit (n=503) (adjusted rate ratio: 1.00; 95% CI, 0.65-1.53). CONCLUSION: Among HIV-seropositive women, BV was not associated with an increased risk of HSIL or cervical lesion progression.

Detection of fastidious vaginal bacteria in women with HIV infection and bacterial vaginosis.

BACKGROUND: Fastidious bacteria have been associated with bacterial vaginosis (BV) using PCR methods. We assessed the prevalence of these bacteria in HIV-1 infected women and their relationship with vaginal pH and shedding of HIV-1 RNA. METHODS: 64 cervicovaginal lavage (CVL) samples were collected from 51 women. Vaginal microbiota were characterized using 8 bacterium-specific quantitative PCR assays. RESULTS: Women with the fastidious bacteria Bacterial Vaginosis Associated Bacterium (BVAB) 1, 2, and 3 showed a trend to increased HIV-1 shedding (OR 2.59-3.07, P = .14-.17). Absence of Lactobacillus crispatus (P < .005) and presence of BVAB2 (P < .001) were associated with elevated vaginal pH. BVAB1, 2, and 3 were highly specific indicators of BV in HIV-infected women, with specificities of 89%-93%. CONCLUSIONS: Fastidious bacteria (BVAB 1, 2, and 3) remain specific indicators of BV in HIV-infected women, and BVAB2 may contribute to the elevated vaginal pH that is a hallmark of this syndrome.