Dataset Information

Randomized Cross-Sectional Study to Compare HIV-1 Specific Antibody and Cytokine Concentrations in Female Genital Secretions Obtained by Menstrual Cup and Cervicovaginal Lavage.

ABSTRACT:

Introduction

Optimizing methods for genital specimen collection to accurately characterize mucosal immune responses is a priority for the HIV prevention field. The menstrual cup (MC) has been proposed as an alternative to other methods including cervicovaginal lavage (CVL), but no study has yet formally compared these two methods.

Methods

Forty HIV-infected, antiretroviral therapy-naïve women from the CAPRISA 002 acute HIV infection cohort study were randomized to have genital fluid collected using the MC with subsequent CVL, or by CVL alone. Qualitative data, which assessed levels of comfort and acceptability of MC using a 5-point Likert scale, was collected. Luminex multiplex assays were used to measure HIV-specific IgG against multiple gene products and 48 cytokines.

Results

The majority (94%) of participants indicated that insertion, wearing and removal of the MC was comfortable. Nineteen MCs with 18 matching, subsequent CVLs and 20 randomized CVLs were available for analysis. Mucosal IgG responses against four HIV-antigens were detected in 99% of MCs compared to only 80% of randomized CVLs (p = 0.029). Higher specific antibody activity and total antibodies were observed in MCs compared to CVL (all p<0.001). In MCs, 42/48 (88%) cytokines were in the detectable range in all participants compared to 27/48 (54%) in CVL (p<0.001). Concentrations of 22/41 cytokines (53.7%) were significantly higher in fluid collected by MC. Both total IgG (r = 0.63; p = 0.005) and cytokine concentrations (r = 0.90; p<0.001) correlated strongly between MC and corresponding post-MC CVL.

Conclusions

MC sampling improves the detection of mucosal cytokines and antibodies, particularly those present at low concentrations. MC may therefore represent an ideal tool to assess immunological parameters in genital secretions, without interfering with concurrent collection of conventional CVL samples.

SUBMITTER: Archary D

PROVIDER: S-EPMC4492781 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

Randomized Cross-Sectional Study to Compare HIV-1 Specific Antibody and Cytokine Concentrations in Female Genital Secretions Obtained by Menstrual Cup and Cervicovaginal Lavage.

Archary Derseree D Liebenberg Lenine J LJ Werner Lise L Tulsi Sahil S Majola Nelisile N Naicker Nivashnee N Dlamini Sarah S Hope Thomas J TJ Samsunder Natasha N Abdool Karim Salim S SS Morris Lynn L Passmore Jo-Ann S JA Garrett Nigel J NJ

PloS one 20150706 7

<h4>Introduction</h4>Optimizing methods for genital specimen collection to accurately characterize mucosal immune responses is a priority for the HIV prevention field. The menstrual cup (MC) has been proposed as an alternative to other methods including cervicovaginal lavage (CVL), but no study has yet formally compared these two methods.<h4>Methods</h4>Forty HIV-infected, antiretroviral therapy-naïve women from the CAPRISA 002 acute HIV infection cohort study were randomized to have genital flu ...[more]

PMID: 26147923

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Project description:BackgroundGiven the potentially causal association of female genital schistosomiasis (FGS) with HIV-1 infection, improved diagnostics are urgently needed to scale-up FGS surveillance. The BILHIV (bilharzia and HIV) study assessed the performance of home-based self-collection methods (cervical and vaginal swabs) compared to cervicovaginal lavage (CVL) for the detection of Schistosoma DNA by real-time polymerase chain reaction (PCR).MethodsBetween January and August 2018, a consecutive series of female participants from the Population-Cohort of the previous HIV prevention trial HPTN 071 (PopART), resident in Livingstone, Zambia were invited to take part in BILHIV if they were 18-31 years old, non-pregnant and sexually active. Genital self-collected swabs and a urine specimen were obtained and a questionnaire completed at home visits. CVL was obtained at clinic follow-up.Results603 women self-collected genital swabs. Of these, 527 women had CVL performed by a mid-wife during clinic follow-up. Schistosoma DNA was more frequently detected in genital self-collected specimens (24/603, 4.0%) compared to CVL (14/527, 2.7%). Overall, 5.0% (30/603) women had female genital schistosomiasis, defined as a positive PCR by any genital sampling method (cervical swab PCR, vaginal swab PCR, or CVL PCR) and 95% (573/603) did not have a positive genital PCR. The sensitivity of any positive genital self-collected swab against CVL was 57.1% (95% CI 28.9-82.3%), specificity 97.3% (95.5-98.5%). In a subset of participants with active schistosome infection, determined by detectable urine Circulating Anodic Antigen (CAA) (15.1%, 91/601), positive PCR (4.3%, 26/601), or positive microscopy (5.5%, 33/603), the sensitivity of any positive self-collected specimen against CVL was 88.9% (51.8-99.7%).ConclusionsGenital self-sampling increased the overall number of PCR-based FGS diagnoses in a field setting, compared with CVL. Home-based sampling may represent a scalable alternative method for FGS community-based diagnosis in endemic resource limited settings.

Project description:Mucosal immunity of the female genital tract plays a critical role in defense against sexually transmitted infections like HIV. Pregnancy is associated with both structural and immunologic alterations in the genital mucosa, but the impact of these changes on its ability to suppress HIV infection is unknown. Current epidemiologic data are conflicting as to whether pregnancy increases the risk of HIV acquisition.The purpose of this study was to define the association between antimicrobial peptides and chemokines in cervicovaginal secretions and in vitro HIV infectivity among pregnant and nonpregnant women.Forty pregnant and 37 nonpregnant women were enrolled in a prospective longitudinal cohort study at a single tertiary care women's hospital in Providence, RI. Cervicovaginal lavage was performed at each study visit. For pregnant women, study visits occurred once per trimester, and there was an optional postpartum visit. For nonpregnant women, study visits occurred across a single cycle that was timed to occur in the proliferative, ovulatory, and secretory phases based on the presumption of a regular menstrual cycle. The impact of cervicovaginal lavage on HIV infectivity was evaluated using a TZM-bl assay and compared between pregnant and nonpregnant women for each visit. The previously validated TZM-bl assay, which uses a luciferase reporting gene to indicate HIV infection of TZM-bl cells, was measured with a luminometer with higher relative light units that indicate greater levels of in vitro HIV infection. Immune mediators were measured with a multiplex bead assay. HIV infectivity and median concentration of each mediator were compared between pregnant and nonpregnant groups with the Wilcoxon rank sum test.Cervicovaginal fluid from pregnant and nonpregnant women significantly decreased HIV infectivity in both groups compared with positive control (virus only; P<.01), but infectivity was not different between groups (P?.44). During the second and third trimesters, pregnant women experienced suppression of several cervicovaginal immune mediators that included human beta defensin-2; lactoferrin; macrophage inflammatory protein-3?; regulated on activation, normally T-cell expressed and secreted; and stromal cell-derived factor-1 (all P?.05). The antimicrobial peptide elafin was significantly correlated with HIV infectivity in both groups across all visits, except at the postpartum visit in the pregnant group (n=16). Secretory leukocyte protease inhibitor also was correlated significantly with infectivity across all visits, but in nonpregnant women only (P?.03).Cervicovaginal secretions from both pregnant and nonpregnant women contain immune mediators that are associated with HIV infectivity in an in vitro assay; however, infectivity was not different between pregnant and nonpregnant groups. If pregnant women are at increased risk for HIV infection, it is unlikely to be mediated by alterations in the effectiveness of these protective secretions.

Project description:While the link between the cervicovaginal bacterial microbiome, human papillomavirus (HPV) infection, and cervical cancer is recognized (P. Łaniewski, D. Barnes, A. Goulder, H. Cui, et al., Sci. Rep. 8:7593, 2018, http://dx.doi.org/10.1038/s41598-018-25879-7; A. Mitra, D. A. MacIntyre, Y. S. Lee, A. Smith, et al., Sci. Rep. 5:16865, 2015, http://dx.doi.org/10.1038/srep16865; A. Mitra, D. A. MacIntyre, J. R. Marchesi, Y. S. Lee, et al., Microbiome 4:58, 2016, http://dx.doi.org/10.1186/s40168-016-0203-0; J. Norenhag, J. Du, M. Olovsson, H. Verstraelen, et al., BJOG, 127:171-180, 2020, http://dx.doi.org/10.1111/1471-0528.15854; E. O. Dareng, B. Ma, A. O. Famooto, S. N. Adebamowo, et al., Epidemiol. Infect. 144:123-137, 2016, http://dx.doi.org/10.1017/S0950268815000965; A. Audirac-Chalifour, K. Torres-Poveda, M. Bahena-Roman, J. Tellez-Sosa et al., PLoS One 11:e0153274, 2016, http://dx.doi.org/10.1371/journal.pone.0153274; M. Di Paola, C. Sani, A. M. Clemente, A. Iossa, et al., Sci. Rep. 7:10200, 2017, http://dx.doi.org/10.1038/s41598-017-09842-6), the role of the cervicovaginal virome remains poorly understood. In this pilot study, we conducted metagenomic next-generation sequencing of cervicovaginal lavage specimens to investigate the relationship between the cervicovaginal DNA virome, bacterial microbiome, genital inflammation, and HPV infection. Specific virome alterations were associated with features of the local microenvironment related to HPV persistence and progression to cervical cancer. Cervicovaginal viromes clustered distinctly by genital inflammation state. Genital inflammation was associated with decreased virome richness and alpha diversity and an increased abundance of Anelloviridae species from the genus Alphatorquevirus. Lactobacillus bacteriophages were closely associated with increased Lactobacillus abundance, consistent with phage-host relationships. Interestingly, bacteria-bacteriophage transkingdom interactions were linked to genital inflammation and showed specific interactions with bacterial vaginosis-associated bacteria, including Gardnerella, Prevotella, and Sneathia. Taken together, our results reveal prominent virome interactions with features of the cervicovaginal microenvironment that are associated with HPV and cervical cancer. These findings expand our understanding of the cervicovaginal host-microbiome interactions in women's health. IMPORTANCE HPV infection is an established risk factor for cervical cancer. However, more broadly, the role of the cervicovaginal virome in cervical cancer progression is not well understood. Here, we identified cervicovaginal DNA virome alterations associated with local microenvironment factors (vaginal microbiota and genital inflammation) that influence HPV persistence and progression to cervical cancer. These findings indicate that the cervicovaginal virome plays an important role in women's health.

Dataset Information

Randomized Cross-Sectional Study to Compare HIV-1 Specific Antibody and Cytokine Concentrations in Female Genital Secretions Obtained by Menstrual Cup and Cervicovaginal Lavage.

Introduction

Methods

Results

Conclusions

Publications

Randomized Cross-Sectional Study to Compare HIV-1 Specific Antibody and Cytokine Concentrations in Female Genital Secretions Obtained by Menstrual Cup and Cervicovaginal Lavage.

Similar Datasets

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