Genital Tract Secretions Research Articles

Prevalence of Four Sexually Transmitted Infection Pathogens Detected in Urine and Genital Tract Secretion in Hangzhou, China.

Sexually transmitted infections (STIs) increase gradually and have become a public health problem in the world. UU, CT, NG, and MG are four common STI pathogens. Our retrospective study analyzed the clinical situation and the laboratory data of patients infected with the four pathogens. The prevalence of the four pathogens, detected in urine and genital tract secretion, was studied in Hangzhou, China. A total of 3,168 male and female patients were randomly selected from February 2023 to February 2024. Urine and genital secretions were collected, and four STI pathogens were controlled for detection. Data were collected from the hospital's electronic medical records, and SPSS 25.0 software was used to perform a statistical analysis. Among 3,168 patients, a total of 1,527 were detected as positive, and the positive rate was 48.20%. The age of patients ranged from 13 - 98 years, with an average age of 45.6. The total of patients consisted of 2,191 males and 977 females, which had a significant difference (p < 0.05). Specimens were mainly collected from the Department of Dermatovenerology, Urological Surgery, Obstetrics and Gynecology, and so on. The positive rate was statistically different between male and female patients (p < 0.05). Single infection performed a main role and accounted for 79.57% of all of the positive patients. In the ≤ 20 age group, the positive rate was the highest and was as high as 77.65%. In detail, single infection caused by UU dominated, especially in the 21 - 30 age group. Double infection caused by UU and CT and triple infection caused by UU, CT, and NG were the majority, both especially in the 21 - 30 age group. There were significant differences in the positive rates in the different age groups and in the four pathogens (p < 0.05). Quadruple infection was very rare and had only been detected in one patient. The prevalence of the four pathogens in Hangzhou was different from other regions. More male than female patients, more single than multiple infections, and more single and multiple infections occurring in young people were the features in Hangzhou. The study would provide reference for prevention, diagnosis, and treatment of STI.

Stability, enrichment, and quantification of total and HPV16-specific IgG present in first-void urine

First-void urine (FVU) samples, containing human papillomavirus (HPV)-specific IgG from female genital tract secretions, provide a non-invasive option for disease monitoring and vaccine impact assessment. This study explores the utility of FVU for IgG quantification, exploring stability and compatibility with DNA preservation methods, alongside various IgG enrichment methods. Healthy female volunteers provided FVU and serum samples. FVU was collected with or without urine conservation medium (UCM) and stored under different conditions before freezing at −80 °C. Four IgG enrichment methods were tested on FVU samples. All samples were analyzed using three total human IgG quantification assays and an in-house HPV16-specific IgG assay. Samples stored with UCM buffer had higher total and HPV16-specific IgG concentrations (p ≤ 0.01) and IgG remained stable for at least 14 days at room temperature. Among IgG enrichment methods, Amicon filtration (AM) and AM combined with Melon Gel purification (AM-MG) provided similar HPV16-IgG concentrations, correlating strongly with serum levels. Protein G magnetic beads methods were incompatible with time-resolved fluorescence-based assays. This study highlights FVU as a reliable and convenient sample for IgG quantification, demonstrating stability for at least 14 days at room temperature and compatibility with UCM DNA preservation. It emphasizes the need to select appropriate IgG enrichment methods and confirms the suitability of both AM and AM-MG methods, with a slightly better performance for AM-MG.

HPV-specific antibodies in female genital tract secretions captured via first-void urine retain their neutralizing capacity

ABSTRACT Human papillomavirus (HPV) vaccines, primarily relying on neutralizing antibodies, have proven highly effective. Recently, HPV-specific antibodies have been detected in the female genital tract secretions captured by first-void urine (FVU), offering a minimally invasive diagnostic approach. In this study, we investigated whether HPV16-specific antibodies present in FVU samples retain their neutralizing capacity by using pseudovirion-based neutralization assays. Paired FVU and serum samples (vaccinated n = 25, unvaccinated n = 25, aged 18–25) were analyzed using two orthogonal pseudovirion-based neutralization assays, one using fluorescence microscopy and the other using luminescence-based spectrophotometry. Results were compared with HPV16-specific IgG concentrations and correlations between neutralizing antibodies in FVU and serum were explored. The study demonstrated the presence of neutralizing antibodies in FVU using both pseudovirion-based neutralization assays, with the luminescence-based assay showing higher sensitivity for FVU samples, while the fluorescence microscopy-based assay exhibited better specificity for serum and overall higher reproducibility. High Spearman correlation values were calculated between HPV16-IgG and HPV16-neutralizing antibodies for both protocols (rs: 0.54–0.94, p < .001). Significant Spearman correlations between FVU and serum concentrations were also established for all assays (rs: 0.44–0.91, p < .01). This study demonstrates the continued neutralizing ability of antibodies captured with FVU, supporting the hypothesis that HPV vaccination may reduce autoinoculation and transmission risk to the sexual partner. Although further protocol optimizations are warranted, these findings provide a foundation for future research and larger cohort studies that could have implications for the optimal design, evaluation, and implementation of HPV vaccination programs.

Concentration strategies for spiked and naturally present biomarkers in non-invasively collected first-void urine

BackgroundFirst-void urine (FVU) provides a non-invasive method for collecting a wide range of biomarkers found in genital tract secretions. To optimize biomarker collection in FVU, this study investigated the impact of naturally present and supplemented precipitating agents: uromodulin (UMOD) and polyethylene glycol (PEG), on the concentration of human papillomavirus (HPV) pseudovirions (PsV), cell-free DNA (cfDNA), and cellular genomic DNA (gDNA) through centrifugation.MethodsFVU samples from ten healthy female volunteers, along with a control sample, were spiked with seal herpesvirus 1 (PhHV-1) DNA, HPV16 plasmid DNA, and HPV16 PsV with an enhanced green fluorescent protein (EGFP) reporter. The samples were subjected to various concentration protocols involving PEG precipitation, low-speed centrifugation (5 min at 1000×g), and medium-speed centrifugation (1 h at 3000×g). Subsequently, quantitative PCR (qPCR) was used to assess cellular and cell-free glyceraldehyde-3-phosphate dehydrogenase (GAPDH) DNA, cell-free PhHV-1 and HPV16 DNA, and PsV (EGFP) DNA. In addition, UMOD levels were measured.ResultsThe findings revealed that PEG significantly increased the concentration of cfDNA and gDNA in the pellet after centrifugation, with the most pronounced effect observed for cfDNA. Moreover, low-speed centrifugation without PEG effectively depleted cellular gDNA while preserving cfDNA in the supernatants. Pseudovirions were consistently pelleted, even with low-speed centrifugation, and a positive but not significant effect of PEG on PsV (EGFP) DNA yield in the pellet was observed. Additionally, a significant correlation was observed between UMOD and GAPDH, HPV16, and PsV (EGFP) DNA quantities in the pellet. Furthermore, large variations among the FVU samples were observed.ConclusionsWith this study, we provide novel insights into how various biomarker precipitation protocols, including both the properties of FVU and the use of PEG as a precipitating agent, influence the concentration of cfDNA, cellular gDNA, and pseudovirions.

Invaplex functions as an intranasal adjuvant for subunit and DNA vaccines co-delivered in the nasal cavity of nonhuman primates

Development of intranasal vaccines for HIV-1 and other mucosal pathogens has been hampered by the lack of adjuvants that can be given safely to humans. We have found that an intranasal Shigella vaccine (Invaplex) which is well tolerated in humans can also function as an adjuvant for intranasal protein and DNA vaccines in mice. To determine whether Invaplex could potentially adjuvant similar vaccines in humans, we simultaneously administered a simian immunodeficiency virus (SIV) envelope (Env) protein and DNA encoding simian-human immunodeficiency virus (SHIV) with or without Invaplex in the nasal cavity of female rhesus macaques. Animals were intranasally boosted with adenoviral vectors expressing SIV env or gag,pol to evaluate memory responses. Anti-SIV antibodies in sera and nasal, genital tract and rectal secretions were quantitated by ELISA. Intracellular cytokine staining was used to measure Th1-type T cells in blood. Macaques given DNA/protein immunizations with 0.5 mg Invaplex developed greater serum IgG, nasal IgA and cervicovaginal IgA responses to SIV Env and SHIV Gag,Pol proteins when compared to non-adjuvanted controls. Rectal IgA responses to Env were only briefly elevated and not observed to Gag,Pol. Invaplex increased frequencies of IFNγ-producing CD4 and CD8 T cells to the Env protein, but not T cell responses induced by the DNA. Ad-SIV boosting increased Env-specific polyfunctional T cells and Env- and Gag,Pol-specific antibodies in serum and all secretions. The data suggest that Invaplex could be highly effective as an adjuvant for intranasal protein vaccines in humans, especially those intended to prevent infections in the genital or respiratory tract.

Evaluation of different culture media to support in vitro growth and biofilm formation of bacterial vaginosis-associated anaerobes.

BackgroundBacterial vaginosis (BV) is one of the most common vaginal infections worldwide. It is associated with the presence of a dense polymicrobial biofilm on the vaginal epithelium, formed mainly by Gardnerella species. The biofilm also contains other anaerobic species, but little is known about their role in BV development.AimTo evaluate the influence of different culture media on the planktonic and biofilm growth of six cultivable anaerobes frequently associated with BV, namely Gardnerella sp., Atopobium vaginae, Lactobacillus iners, Mobiluncus curtisii, Peptostreptococcus anaerobius and Prevotella bivia.MethodsA total of nine different culture media compositions, including commercially available and chemically defined media simulating genital tract secretions, were tested in this study. Planktonic cultures and biofilms were grown under anaerobic conditions (10% carbon dioxide, 10% helium and 80% nitrogen). Planktonic growth was assessed by optical density measurements, and biofilm formation was quantified by crystal violet staining.ResultsSignificant planktonic growth was observed for Gardnerella sp., A. vaginae and L. iners in New York City III broth, with or without ascorbic acid supplementation. Biofilm quantification showed high in vitro biofilm growth for Gardnerella sp., P. anaerobius and P. bivia in almost all culture media excluding Brucella broth. Contrary, only New York City III broth was able to promote biofilm formation for A. vaginae, L. iners and M. curtisii.ConclusionsOur data demonstrate that New York City III broth relative to the other tested media is the most conducive for future studies addressing polymicrobial biofilms development as this culture medium allowed the formation of significant levels of single-species biofilms.

Antibacterial Activity of Lactobacillus Strains Isolated from Mongolian Yogurt against Gardnerella vaginalis

Worldwide interest in the use of functional foods containing probiotic bacteria such as Lactobacillus and Bifidobacterium for health promotion and disease prevention has increased significantly. Probiotics have demonstrated beneficial properties including strengthening the body's natural defense system, inhibiting the growth of pathogenic bacteria, and regulating mental activity, but their effects on the human vagina have not been fully elucidated. The primary purpose of our study was to isolate Lactobacillus strains from old yogurt, a traditional dairy product, and investigate their probiotic potential with respect to the human vaginal system. Four Lactobacillus plantarum (L. plantarum) strains, named ZX1, ZX2, ZX27, and ZX69, were isolated from the yogurt samples. Simultaneously, we used a commercial Lactobacillus strain (Lactobacillus delbrueckii DM8909) as a control strain. We tested the antimicrobial activity of Lactobacillus isolates against Escherichia coli and Gardnerella vaginalis by agar spot and well diffusion tests. Then, we tested the antibiotic susceptibility of the 5 strains by using the minimal inhibitory concentration method. We attempted to detect possible bacteriocin genes by PCR sequencing technique. Using a chemically defined medium simulating genital tract secretions, we found that the selected Lactobacillus strains could alter the expression of known virulence genes in Gardnerella vaginalis. Bacteriocins derived from these isolated strains had potent antibacterial activity against G. vaginalis and E. coli, with the most effective activity observed in the case of ZX27. In addition, all strains including the L. delbrueckii DM8909 were positive for the presence of the plantaricin cluster of genes described in L. plantarum C11. The tested stains possessed the pln gene indicating that one of the antibacterial agents was plantaricin. We assume that the production of antimicrobial substances such as bacteriocins induce G. vaginalis to upregulate antimicrobial resistance genes. The new isolated strains have bacteriocin-related genes and can change the antimicrobial resistance gene transcription of G. vaginalis.

Hepatitis B Vaccination Induces Mucosal Antibody Responses in the Female Genital Tract, Indicating Potential Mechanisms of Protection Against Infection.

Vaccines against hepatitis B virus confer effective protection. Enzyme-linked immunosorbent assay was developed to test for specific antibodies in female genital tract secretions. Anti-hepatitis B IgG and IgA were detected in the cervicovaginal secretions of women after hepatitis B vaccination, indicating a potential genital tract role for neutralizing antibodies against sexually transmitted hepatitis B virus.

J-107 Interrogating the immunologic and microbial cervical microenvironment in HPV infection

Infection with high-risk human papillomavirus (hrHPV) infection in the oral and anogenital mucosa has been confirmed to be a necessary but insufficient cause of invasive cervical cancer (ICC), which is a leading cause of cancer incidence and mortality worldwide. Over the past 2 decades, our understanding of the natural history of cervical hrHPV infection has evolved, especially with regard to the influence of co-infections and the dynamics of the cervical microenvironment. For example, it is now recognized that at least a proportion of hrHPV infections are immunologically controlled for long periods of time in an undetectable (latent) state, at risk of recurrent detection (reactivation) upon immune suppression.1 This phenomenon is most clearly illustrated when comparing the HPV natural history in HIV-infected and HIV-uninfected individuals, where both incident and persistent detection of HPV is proportionally increased with increasing immune suppression.2 Multiple new type cervical HPV detection increases nearly 4-fold within weeks of acute HIV infection, suggesting a key role for tissue resident T-cell memory in control of latent HPV infection.3 In HIV-uninfected women, we have observed polarization toward T-helper type 2 immune profiles of the lower genital tract immune microenvironment. In an older, well-screened US population, HPV positive women exhibited immune profiles similar to those described in allergic inflammation.4 In the developing world, we have reported an increased prevalence of HPV infection at older ages in Amazonian women with soil-transmitted helminth (STH) infection, who showed evidence of Th2-skewed immunity in lower genital tract secretions compared with STH-uninfected women.5 This epidemiologic evidence, combined with experimental animal models of papillomavirus infection, collectively implicate a key role of host immunity in the control of cervical HPV infection and, by extension, risk of cervical cancer. This presentation will make a case that the time has come to move human HPV natural history studies away from traditional designs with large sample sizes and long interval censored sampling (eg, every 6 months) to designs with smaller sample sizes and more frequent sampling density (eg, every week) to allow interrogation of the dynamic interplay between the shifting microenvironment and HPV detection. Prioritizing a focus on understanding the dynamics and immune mediators involved in healthy control of HPV infection may be an overlooked fundamental system component required to fully understand the causes of dysregulation of HPV infection and persistent detection. This represents a paradigm shift in studying the molecular epidemiology of human viral infections, reflects more fully a systems approach to understanding biological complexity, and may lead to development of less invasive interventions at earlier stages in viral natural history to prevent severe pathological outcomes. REFERENCES 1. Gravitt PE. The known unknowns of HPV natural history. J Clin Invest. 2011;121:4593–4599. 2. Strickler HD, Burk RD, Fazzari M, et al. Natural history and possible reactivation of human papillomavirus in human immunodeficiency virus-positive women. J Natl Cancer Inst. 2005;97:577–586. 3. Nowak RG, Gravitt PE, Morrison CS, et al. Increases in human papillomavirus detection during early HIV infection among women in Zimbabwe. J Infect Dis. 2011;203:1182–1191. 4. Marks MA, Viscidi RP, Chang K, et al. Differences in the concentration and correlation of cervical immune markers among HPV positive and negative perimenopausal women. Cytokine. 2011;56:798–803. 5. Gravitt PE, Marks M, Kosek M, et al. Soil-transmitted helminth infections are associated with an increase in human papillomavirus prevalence and a T-helper type 2 cytokine signature in cervical fluids. J Infect Dis. 2016;213:723–730.

Viral metagenomics reveals significant viruses in the genital tract of apparently healthy dairy cows.

The virome in genital tract secretion samples collected from 80 dairycattle in Shanghai, China, was characterized. Viruses detected included members of the families Papillomaviridae, Polyomaviridae, Hepeviridae, Parvoviridae, Astroviridae, Picornaviridae, and Picobirnaviridae. A member of a new species within the genus Dyoxipapillomavirus and six circular Rep-encoding single-stranded DNA (ssDNA) (CRESS-DNA) viral genomes were fully sequencedand phylogenetically analyzed. The prevalence of bovine polyomaviruses 1 and 2 was measured by PCR to be 10% (8/80) and 6.25% (5/80), respectively.PCR screening also indicated that the novel papillomavirus ujs-21015 and bovine herpesvirus 6 were present in three and two out of the 80 samples, respectively.

Interferon epsilon in the reproductive tract of healthy and genital herpes simplex virus-infected pregnant women: Results of a pilot study.

Recently characterized interferon epsilon (IFNe) protects against sexually transmitted infections, including genital herpes simplex virus (HSV), in animal models. There are no reports of IFNe in genital tract secretions of pregnant women, and data on IFNe in non-pregnant women are limited. This pilot study is the first to measure concentrations of IFNe in vaginal and cervical secretions during pregnancy and compare values between healthy and genital HSV-infected women. Vaginal or cervical specimens from 30 pregnant women were obtained from the Global Alliance to Prevent Prematurity and Stillbirth (GAPPS) repository. Cervical samples were collected during the first trimester and vaginal samples across pregnancy. Enzyme-linked immunosorbent assay determined concentrations of IFNe (pg/mL). Data for IFNe were log-transformed and compared by maternal demographics, clinical variables, and HSV status using t tests and linear regression. Repeated measures analysis explored trends across pregnancy. Among the entire cohort, first trimester concentrations of IFNe in vaginal or cervical secretions decreased as body mass index increased (β=-0.14, P=.0466). Concentrations of vaginal IFNe increased across pregnancy in HSV-infected and healthy women (P=.009). Average vaginal IFNe across pregnancy was lower in women with HSV compared to healthy women (P=.0009). Interferon epsilon increased across pregnancy, but was less abundant in women with HSV. This pilot investigation cannot make any definitive conclusions. However, animal models suggest that IFNe may protect against STIs. Thus, larger studies are required to validate expression of IFNe in the reproductive tract of pregnant women with and without genital infections.

Lactobacillus crispatus represses vaginolysin expression by BV associated Gardnerella vaginalis and reduces cell cytotoxicity

Using a chemically-defined medium simulating genital tract secretions, we have shown that pre-adhering Lactobacillus crispatus to Hela epithelial cells reduced cytotoxicity caused by Gardnerella vaginalis. This effect was associated to the expression of vaginolysin and was specific to L. crispatus interference, as other vaginal facultative anaerobes had no protective effect.

Novel approaches to early detection of endometrial cancer.

Detection of endometrial cancer at an early stage leads to better oncologic outcomes. To date, a screening test for endometrial cancer does not exist. Evolving knowledge of molecular changes involved in endometrial cancer carcinogenesis paired with sensitive and high-throughput technological advancements are a promising combination that can be leveraged to detect tumor DNA and proteins. These molecular biomarkers can be identified in biospecimens collected via minimally invasive and noninvasive approaches. Exploiting lower genital tract secretions as a biospecimen also allows for patient self-sampling. Successful development of a screening test for endometrial cancer using self-collected lower genital tract biospecimens has the potential to increase accessibility to care and improve patient compliance.

Reduced Levels and Bioactivity of Endogenous Protease Cathepsin D in Genital Tract Secretions of Postmenopausal Women.

Reduced Levels and Bioactivity of Endogenous Protease Cathepsin D in Genital Tract Secretions of Postmenopausal Women.

Evaluation on the detection methods of group B Streptococcus in late pregnancy

Objective To evaluate the detection methods of group B Streptococcus(GBS) in late pregnancy. Methods A total of 300 cases of prenatal genital tract secretion samples in late pregnancy were detected for GBS by broth enrichment switched to blood plate method,screening for GBS cultivation medium method and polymerase chain reaction(PCR). Methodological evaluation was performed. Results The detection rates of GBS by broth enrichment switched to blood plate method and screening for GBS cultivation medium method were 5.3%and 7.0%, without statistical significance(P>0.05). The detection rate of GBS by PCR was 9.6%,and there was statistical significance with the other 2 methods(P<0.05). Conclusions PCR is a good choice for GBS detection in late pregnancy. It can be used in the rapid detection of GBS for pregnant women before delivery.

Analysis of the sex ratio of reported gonorrhoea incidence in Shenzhen, China

ObjectiveTo assess the clinical process of gonorrhoea diagnosis and report in China, and to determine the difference of sex ratio between reported incidence based on reporting data and true diagnosis...

Genital Shedding of Resistant Human Immunodeficiency Virus-1 Among Women Diagnosed With Treatment Failure by Clinical and Immunologic Monitoring.

Background. The accumulation of human immunodeficiency virus (HIV) resistance mutations can compromise treatment outcomes and promote transmission of drug-resistant virus. We conducted a study to determine the duration and evolution of genotypic drug resistance in the female genital tract among HIV-1-infected women failing first-line therapy. Methods. Treatment failure was diagnosed based on World Health Organization (WHO) clinical or immunologic criteria, and second-line therapy was initiated. Stored plasma and genital samples were tested to determine the presence and timing of virologic failure and emergence of drug resistance. The median duration of genital shedding of genotypically resistant virus prior to regimen switch was estimated. Results. Nineteen of 184 women were diagnosed with treatment failure, of whom 12 (63.2%) had confirmed virologic failure at the switch date. All 12 women with virologic failure (viral load, 5855-1 086 500 copies/mL) had dual-class resistance in plasma. Seven of the 12 (58.3%) had genital HIV-1 RNA levels high enough to amplify (673-116 494 copies/swab), all with dual-class resistance. The median time from detection of resistance in stored samples to regimen switch was 895 days (95% confidence interval [CI], 130-1414 days) for plasma and 629 days (95% CI, 341-984 days) for genital tract secretions. Conclusions. Among women diagnosed with treatment failure using WHO clinical or immunologic criteria, over half had virologic failure confirmed in stored samples. Resistant HIV-1 RNA was shed in the genital tract at detectable levels for ≈1.7 years before failure diagnosis, with steady accumulation of mutations. These findings add urgency to the ongoing scale-up of viral load testing in resource-limited settings.

Activity of Genital Tract Secretions and Synthetic Antimicrobial Peptides against Group B Streptococcus.

Genital tract secretions inhibit Escherichia coli (E. coli) through antimicrobial peptides (AMP) secreted by the host and vaginal microbiota. However, there are limited data against group B Streptococcus (GBS). Group B Streptococcus were incubated with cervico-vaginal lavage (CVL) samples from healthy non-pregnant women (n = 12) or synthetic AMP and monitored for bacterial growth using a turbidimetric approach. E. coli inhibitory activity was determined by a colony-forming unit assay. None of the CVL samples inhibited GBS. The human neutrophil peptide-1 and human defensin 5 inhibited GBS growth by ≥80% at concentrations ≥20 μg/mL and ≥50 μg/mL, respectively, while human beta-defensin 2 and LL-37 did not inhibit at highest concentration tested (100 μg/mL). In contrast, all AMP inhibited E. coli. Antimicrobial peptides may protect against E. coli colonization but have more limited activity against GBS. Future studies will focus on augmenting host defense with specific AMP to prevent genitourinary infection with these pathogenic organisms.

Early-life exposures to infectious agents and later cancer development.

There is a growing understanding that several infectious agents are acquired in early life and this is the reason why available vaccines target the new born, infants, and adolescents. Infectious agents are associated with cancer development and it is estimated that about 20% of the world's cancer burden is attributed to infectious agents. There is a growing evidence that certain infectious agents acquired in early life can give rise to cancer development, but estimates of the cancer burden from this early‐life acquisition is unknown. In this article, we have selected five cancers (cervical, liver, Burkitt's lymphoma‐leukemia, nasopharyngeal carcinoma, and adult T‐cell leukemia‐lymphoma) and examine their links to infectious agents (HPV, HBV, HCV, EBV, and HTLV‐1) acquired in early life. For these agents, the acquisition in early life is from mother‐to‐child transmission, perinatal contact (with genital tract secretions, amniotic fluids, blood, and breast milk), saliva, sexual intercourse, and blood transfusion. We also discuss prevention strategies, address future directions, and propose mechanisms of action after a long latency period from the time of acquisition of the infectious agent in early life to cancer development.

Innate Antibacterial Activity in Female Genital Tract Secretions Is Associated with Increased Risk of HIV Acquisition.

Greater inhibitory activity against Escherichia coli and levels of human β defensin (HBD)-2 in genital tract secretions predicted HIV acquisition in women in the HPTN 035 trial. We investigated whether higher levels of E. coli inhibitory activity and antimicrobial peptides in cervicovaginal lavage (CVL) samples predicted HIV acquisition in women in the CAPRISA 002 Acute Infection Study. E. coli inhibitory activity and antimicrobial peptides were quantified in CVL from a subset of CAPRISA 002 participants who did not seroconvert (n=39) and from seroconverting women prior to infection (n=17) and during acute infection (n=11). Women who acquired HIV had significantly greater preinfection CVL E. coli inhibitory activity (p=0.01) and HBD-1 levels (p=0.02) compared to women who remained uninfected. Preinfection E. coli inhibitory activity remained significantly associated with seroconversion following adjustment for the presence of bacterial vaginosis (OR 1.45; 95% CI 1.07, 1.97). Partial least squares discriminant analysis confirmed that preinfection CVL E. coli inhibitory activity, together with higher CVL concentrations of HBD-1 and secretory leukocyte protease inhibitor, distinguished seroconverters from nonseroconverters with 67% calibration accuracy. CVL concentrations of human neutrophil peptides (HNP) 1-3 increased significantly with acute infection (p=0.001) and correlated with plasma viral set point (r=0.66, p=0.03). E. coli inhibitory activity in genital tract secretions could provide a biomarker of HIV risk. The correlation between HNP 1-3 and viral set point merits further investigation of the relationship between mucosal inflammation during early HIV infection and disease progression.