Cervical human papillomavirus (HPV) infection may increase HIV risk. Since other genital infections enhance HIV susceptibility by inducing inflammation, we assessed the impact of HPV infection and ...clearance on genital immunology and the cervico-vaginal microbiome. Genital samples were collected from 65 women for HPV testing, immune studies and microbiota assessment; repeat HPV testing was performed after 6 months. All participants were HIV-uninfected and free of bacterial STIs. Cytobrush-derived T cell and dendritic cell subsets were assessed by multiparameter flow cytometry. Undiluted cervico-vaginal secretions were used to determine cytokine levels by multiplex ELISA, and to assess bacterial community composition and structure by 16S rRNA gene sequence analysis. Neither HPV infection nor clearance were associated with broad differences in cervical T cell subsets or cytokines, although HPV clearance was associated with increased Langerhans cells and HPV infection with elevated IP-10 and MIG. Individuals with HPV more frequently had a high diversity cervico-vaginal microbiome (community state type IV) and were less likely to have an L. gasseri predominant microbiome. In summary, HPV infection and/or subsequent clearance was not associated with inflammation or altered cervical T cell subsets, but associations with increased Langerhans cells and the composition of the vaginal microbiome warrant further exploration.
Background. Genital inflammation is a key determinant of human immunodeficiency virus (HIV) transmission, and may increase HIV-susceptible target cells and alter epithelial integrity. Several genital ...conditions that increase HIV risk are more prevalent in African, Caribbean, and other black (ACB) women, including bacterial vaginosis and herpes simplex virus type-2 (HSV-2) infection. Therefore, we assessed the impact of the genital microbiota on mucosal immunology in ACB women and microbiome-HSV-2 interactions. Methods. Cervicovaginal secretions and endocervical cells were collected by cytobrush and Instead Softcup, respectively. T cells and dendritic cells were assessed by flow cytometry, cytokines by multiplex enzyme-linked immunosorbent assay (ELISA), and the microbiota by 16S ribosomal ribonucleic acid gene sequencing. Results. The cervicovaginal microbiota of 51 participants were composed of community state types (CSTs) showing diversity (20/51; 39%) or predominated by Lactobacillus iners (22/51; 42%), L. crispatus (7/51; 14%), or L. gasseri (2/51; 4%). High-diversity CSTs and specific bacterial phyla (Gardnerella vaginalis and Prevotella bivia) were strongly associated with cervicovaginal inflammatory cytokines, but not with altered endocervical immune cells. However, cervical CD4+ T-cell number was associated with HSV-2 infection and a distinct cytokine profile. Conclusions. This suggests that the genital microbiota and HSV-2 infection may influence HIV susceptibility through independent biological mechanisms.
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.
Objectives
There is speculation, but there are few data, on the high rates of unintended pregnancies in HIV‐positive women. We investigated rates and correlates of unintended pregnancies among ...HIV‐positive women of reproductive age.
Methods
A cross‐sectional study was conducted with recruitment stratified to match the geographical distribution of HIV‐positive women of reproductive age (18–52 years) living in Ontario, Canada. Women, recruited from 38 sites between October 2007 and April 2009, were invited to complete a 189‐item self‐administered survey. This analysis focused on questions relating to pregnancy and whether the last pregnancy was intended. Logistic regression models were fitted to calculate unadjusted and adjusted odds ratios of correlates of unintended pregnancies occurring after HIV diagnosis. Happiness with unintended pregnancies was also assessed.
Results
The median age at the time of the survey of the 416 participating HIV‐positive women who were previously pregnant (53% before and 47% after HIV diagnosis) was 38 years interquartile range (IQR) 33–44 years and their last pregnancy was a median of 8 years (IQR 3–14 years) prior to the survey (n=283). Fifty‐nine per cent were born outside Canada and 47% were of African ethnicity. Of the 416, 56% 95% confidence interval (CI) 51–61% identified that their last pregnancy was unintended (57% before and 54% after HIV diagnosis). In the multivariable model, significant correlates of unintended pregnancy after HIV diagnosis were: marital status (P=0.01) and never having given birth (P=0.01). Women were less happy if their pregnancy was unintended (P<0.01).
Conclusions
The prevalence of unintended pregnancy was high in this cohort. Pregnancy planning programmes are needed for this population to decrease fetal and maternal complications and reduce vertical and horizontal transmission.
The African, Caribbean and Black communities have been found to be reluctant to participate in health research in North America. This is partly attributed to historical experiences as well as their ...cultural beliefs. Cultural beliefs about the uses of breast milk/fluids could further hinder the participation of African, Caribbean, and Black communities in research involving the collection of breast milk/fluids samples.
We conducted 17 in-depth interviews and three group interviews (n = 10) with HIV+ African, Caribbean and Black women living in Ontario, Canada to explore their cultural beliefs about breast milk/fluids and their acceptance of participating in research that involves the provision of breast fluid samples.
Qualitative study involving in-depth interviews.
Our respondents believed that breast milk/fluids should be used for infant feeding and for curative purposes for a variety of children's health ailments as well as ailments experienced by other family members. The cultural belief that breast milk/fluids could be used to bewitch the baby and mother and the perception that it is intrusive (equating breast milk/fluids research to DNA testing), could prevent African, Caribbean and Black women from participating in research involving the collection of breast milk/fluids. Despite these fears, some respondents expressed that they would participate if the research results would benefit them directly, for example, by finding a cure for HIV, enabling HIV+ mothers to breastfeed, or contributing to developing new drugs or vaccines for HIV. Women's recommendations to facilitate successful recruitment included giving incentives to participants, and employing a recruiter who was trustworthy, informed, and culturally sensitive.
Cultural beliefs could present barriers to recruitment and participation of Africa, Caribbean and Black communities in health research involving breast milk/fluid samples. Successful recruitment for future studies would necessitate researchers to be culturally aware of the beliefs held by African, Caribbean and Black women, to build trust, and use an appropriate recruiter. While the findings relate to breast milk/fluids, the suggested recommendations for facilitating recruitment of research participants from these communities may be useful to consider when recruiting ethnically and culturally similar participants for research involving biological samples.
African and Caribbean communities in Canada and other developed countries are disproportionately affected by HIV/AIDS. This qualitative study of African and Caribbean communities in Toronto sought to ...understand HIV-related stigma, discrimination, denial and fear, and the effects of multiple intersecting factors that influence responses to the disease, prevention practices and access to treatment and support services. Semi-structured interviews were conducted with 30 HIV-positive men and women and focus groups were conducted with 74 men and women whose HIV status was negative or unknown. We identified a range of issues faced by African and Caribbean people that may increase the risk for HIV infection, create obstacles to testing and treatment and lead to isolation of HIV-positive people. Our findings suggest the need for greater sensitivity and knowledge on the part of healthcare providers; more culturally specific support services; community development; greater community awareness; and expanded efforts to tackle housing, poverty, racism and settlement issues.
Background: The penis is the primary site of HIV acquisition in heterosexual men. The per-act probability of HIV acquisition is enhanced by the presence of a foreskin, sexually transmitted infections ...(STIs) and/or microbiome dysbiosis, with elevated penile inflammatory cytokines acting as a common central pathway. However, the impact of sex itself on the penile immune milieu is unknown. We hypothesized that condomless penile-vaginal sex would transiently increase penile cytokines, with increases being more profound and sustained in uncircumcised men. Methods: To address this hypothesis we recruited 37 STI-free heterosexual couples to the Sex, Couples and Science Study (SECS), an observational prospective study ran from July to November 2018 through the Women's Health in Women's Hands Clinic (Toronto, Canada). Approximately half of the male partners were circumcised. Baseline penile swabs, semen samples, cervical secretions and blood were collected after a period of abstinence, and 48 hours later couples engaged in either condomless (n=30) or condom-protected (n=8) penile-vaginal sex. One couple participated twice, once in each group. Repeat penile swabs and blood were collected after one to two hours, seven to eight hours and fourty-eight to seventy-two hours. Soluble immune factors were quantified by multiplex immunoassay, and blood immune cell subsets were determined by flow cytometry; the study co-primary immune endpoints were the penile levels of IL-8 and MIG, cytokines previously linked to HIV acquisition. Statistical comparisons were performed using the Wilcoxon Signed Ranked test. Results: One hour after sex there was a dramatic increase in coronal sulcus levels of IL-8 and MIG, regardless of condom use, with a return to baseline by 72 hours; similar patterns were observed for other chemoattractant chemokines. The extent and duration of these increases were similar in circumcised and uncircumcised men, and correlated closely with cytokine levels in the female partner's genital tract (after condomless sex) or in the participant's semen (after condom-protected sex). Conclusions: Relatively sustained increases in penile inflammatory cytokines after penile-vaginal sex appear to reflect penile coating with cervico-vaginal secretions and/or semen. Since external application of cytokines enhanced HIV acquisition in a foreskin explant model, these novel findings have important implications for the biology of penile HIV acquisition.
Background Maternal placental syndromes are associated with adverse fetal outcomes and maternal cardiovascular disease. However, whether HIV infection increases the risk of maternal placental ...syndromes is unknown. Our objective was to compare the risk of maternal placental syndromes between women living with and without HIV infection in Ontario. Methods We conducted a population-based study using health administrative data from Ontario. We identified all pregnancies resulting in a live birth between Apr. 1, 2002, and Mar. 31, 2011; we identified women living with HIV using a validated case-finding algorithm. Our primary composite outcome was maternal placental syndromes, defined as a diagnosis of preeclampsia, eclampsia, placental abruption or placental infarction. We used generalized estimating equations with a logit link function to derive adjusted odds ratios (AORs) and 95% confidence intervals (CI) for the association between HIV infection and maternal placental syndromes. Results Data from 1 132 871 pregnancies were available for analysis; 634 (0.06%) of the pregnancies were in women living with HIV. After multivariable adjustment, we found no difference in the risk of maternal placental syndromes between women living with HIV and those without HIV infection (5.8% v. 5.6%; AOR 0.85 95% CI 0.59-1.21). An increased risk of maternal placental syndromes was associated with pre-existing diabetes (AOR 1.47 95% CI 1.39-1.54), pre-existing hypertension (AOR 4.28 95% CI 4.15-4.42) and chronic kidney disease (AOR 1.83 95% CI 1.61-2.08). Interpretation Women with HIV are not at increased risk of maternal placental syndromes. Our results underscore the importance of optimizing the management of comorbid illness associated with maternal placental syndromes during the prenatal period for all women, irrespective of HIV status.
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