Toll-like receptor gene variants and bacterial vaginosis among HIV-1 infected and uninfected African women.
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ABSTRACT:
SUBMITTER: Mackelprang RD
PROVIDER: S-EPMC4523061 | biostudies-literature | 2015 Jul-Aug
REPOSITORIES: biostudies-literature
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Toll-like receptor gene variants and bacterial vaginosis among HIV-1 infected and uninfected African women.
Mackelprang Romel D RD Scoville Caitlin Wright CW Cohen Craig R CR Ondondo Raphael Omusebe RO Bigham Abigail W AW Celum Connie C Campbell Mary S MS Essex Max M Wald Anna A Kiarie James J Ronald Allan A Gray Glenda G Lingappa Jairam R JR
Genes and immunity 20150430 5
Bacterial vaginosis (BV) is a common vaginal syndrome associated with altered microflora that increases the risk of preterm delivery and acquisition of sexually transmitted diseases. The cause of BV is unknown although toll-like receptors (TLRs), that are central to innate immune responses, may be important. We evaluated associations between TLR SNPs and BV among HIV-1 infected and uninfected African women. Logistic regression was used to assess associations between SNPs (N=99) in TLRs 2-4, 7-9 ...[more]
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Project description:Bacterial vaginosis (BV) is a common vaginal disorder in women of reproductive age, especially among women with HIV-1 infection. Several bacterial products including lipopolysaccharides (LPS), lipoteichoic acids (LTA), and peptidoglycans (PGN) are stimulatory ligands for Toll-like receptors (TLRs), and recent evidence indicates the important role of variation in TLR genes for permitting overgrowth of gram negative and BV-type flora. We assessed whether genetic polymorphisms in five TLR genes (TLR1, TLR2, TLR4, TLR6, and TLR9) could be determinants of differential host immune responses to BV in 159 HIV-1-positive African American adolescents enrolled in the Reaching for Excellence in Adolescent Care and Health (REACH) study. BV was assessed biannually and diagnosed either by a Nugent score of at least 7 of 10, or using the Amsel criteria. Cox-proportional hazards regression models, adjusted for concurrent Chlamydia and Gonorrhea infections, douching, and absolute CD4 cell count, were used to identify host genetic factors associated with BV. Two SNPs were associated with BV as diagnosed by the Nugent score and the combined criteria: a minor allele G of rs4986790 (frequency=0.07), which encodes a His to Tyr substitution in TLR4 (HR=1.47, 95% CI 1.15-1.87) and rs187084 (frequency=0.24) on TLR9. The minor allele of rs1898830 (frequency=0.13) was associated with an increased hazard of BV defined by the Amsel criteria (HR=1.86, 95% CI 1.17-2.95). Further studies are warranted to confirm the associations of TLR gene variants and also to understand the underlying pathways and immunogenetic correlates in the context of HIV-1 infection.
| S-EPMC3518650 | biostudies-literature
Project description:ObjectiveAssess efficacy of intermittent intravaginal metronidazole gel treatment in reducing frequency of bacterial vaginosis (BV).DesignRandomized, double-masked, placebo-controlled phase 3 trial.SettingPostnatal and family planning clinics of the Queen Elizabeth Central Hospital and two health centers in Blantyre, Malawi.ParticipantsNonpregnant HIV-uninfected and -infected women.InterventionIntravaginal metronidazole treatment and placebo gels provided at baseline and every 3 mo for 1 y.Outcome measuresPRIMARY: Cross-sectional and longitudinal comparisons of BV frequency at baseline, 1 mo after product dispensation (post-treatment evaluation [PTE]), and every quarterly visit. Secondary: Effect of treatment on BV clearance and recurrence.ResultsBASELINE: 842 HIV-uninfected and 844 HIV-infected women were enrolled. The frequency of BV at baseline in treatment and placebo arms, respectively, was 45.9% and 46.8% among HIV-uninfected women, and 60.5% and 56.9% among HIV-infected women.Primary outcomesAt the PTEs the prevalence of BV was consistently lower in treatment than placebo arms irrespective of HIV status. The differences were statistically significant mainly in HIV-uninfected women. Prevalence of BV was also reduced over time in both treatment and placebo arms. In a multivariable analysis that controlled for other covariates, the effect of intravaginal metronidazole treatment gel compared with placebo was not substantial: adjusted relative risk (RR) 0.90, 95% confidence interval (CI) 0.83-0.97 in HIV-uninfected women and adjusted RR 0.95, 95% CI 0.89-1.01 in HIV-infected women.Secondary outcomesIntravaginal metronidazole treatment gel significantly increased BV clearance (adjusted hazard ratio [HR] 1.34, 95% CI 1.07-1.67 among HIV-uninfected women and adjusted HR 1.29, 95% CI 1.06-1.58 among HIV-infected women) but was not associated with decreased BV recurrence.SafetyNo serious adverse events were related to use of intravaginal gels.ConclusionIntermittent microbicide treatment with intravaginal gels is an innovative approach that can reduce the frequency of vaginal infections such as BV.
| S-EPMC1851729 | biostudies-literature
Project description:BackgroundFrequency of sex, contraceptive use and HIV infection are key determinants of fertility. Use of an effective family planning (EFP) method (injectable, oral, intra-uterine contraceptive device (IUCD), or Norplant) potentially eliminates women's concerns of unintended pregnancy. We report the association between EFP and frequency of sex among HIV-infected and HIV-uninfected non-pregnant African women.MethodsProspective fertility intentions study nested within a phase 3 randomized double-masked placebo-controlled trial (2003-2005) to treat genital tract infections in HIV-infected and HIV-uninfected non-pregnant women. Enrollment of study participants was stratified by HIV infection status. Data on demographics, family planning and sexual history were obtained at baseline and at 3, 6, 9 and 12 months. Chi square and Wilcoxon Rank-Sum tests were used to compare categorical and continuous variables, respectively. Generalized Estimating Equations method was used to estimate relative risk (RR) of frequent sex (≥ 2 acts/week) among users of different EFP methods (injectable, oral, implant or intra-uterine contraceptive device).ResultsAfter adjusting for age, current health status, and fertility intentions, EFP use was significantly associated with frequent sex among HIV-infected women (RR 1.32; 95% Confidence Interval [CI] 1.14-1.52); this association was not statistically significant among HIV-uninfected women (RR 1.10; 95% CI 0.96-1.24). Fertility intentions among HIV-infected, and education among HIV-uninfected womenwere independent predictors of sex frequency.ConclusionThese data suggest that the association between EFP use and frequency of sex among women varies by HIV infection status. Service-delivery of diverse EFP methods should be integrated within HIV counseling, testing and treatment facilities.Trial registrationRegistration number NCT00140764 under the clinicaltrials.gov, first Posted: September 1, 2005, last Update Posted: August 10, 2011.
| S-EPMC6036664 | biostudies-literature
Project description:BackgroundThe spectrum of bacteria associated with bacterial vaginosis (BV) has recently expanded through taxonomic changes and the use of molecular methods. These methods have yet to be used in large-scale epidemiological studies in Africa where BV is highly prevalent.MethodsAn analysis of samples obtained during a clinical trial of the management of vaginal discharge in four West African countries. Samples were available from 1555 participants; 843 (54%) had BV. Nucleic acids of 13 bacterial genera or species potentially associated with BV were detected through the polymerase chain reaction.ResultsThe associations between various components of the vaginal flora were complex. Excluding Lactobacillus, the other 12 micro-organisms were all associated with each other at the p≤0.001 level. The prevalence of various bacterial genera or species varied according to age, sexual activity and HIV status. In multivariate analysis, the presence of Gardnerella vaginalis, Bifidobacterium, Megasphaera elsdenii, Dialister, Mycoplasma hominis, Leptotrichia, and Prevotella were independently associated with BV as was the absence of Lactobacillus and Peptoniphilus. However, Mobiluncus, Atopobium vaginae, Anaerococcus, and Eggerthella were not independently associated with BV. Unexpectedly, after treatment with a regimen that included either metronidazole or tinidazole, the proportion of patients with a complete resolution of symptoms by day 14 increased with the number of bacterial genera or species present at enrolment.ConclusionsNumerous bacterial genera or species were strongly associated with each other in a pattern that suggested a symbiotic relationship. BV cases with a simpler flora were less likely to respond to treatment. Overall, the vaginal flora of West African women with BV was reminiscent of that of their counterparts in industrialized countries.
| S-EPMC3176826 | biostudies-literature
Project description:There is a health disparity for both bacterial vaginosis (BV) and human immunodeficiency virus type 1 (HIV-1) infection in African American women that may be linked. The evidence that BV predisposes women to higher risk for HIV infection is well documented. The underlying mechanisms to support the epidemiological connections will require further investigations. This review explores the risk factors for BV disease with implications for HIV-1 acquisition in the context of race as a potential driver of the 20-fold increase in HIV-1 acquisition for African American women compared to white women. Specifically, it explores (i) disparities for BV in African American women, (ii) racial disparity for HIV-1 acquisition in African American women, (iii) common factors associated with BV and HIV acquisition in African American women, and (iv) potential mechanisms of the enhancement of HIV-1 transmission by BV.
| S-EPMC4942368 | biostudies-literature
Project description:Background HIV is associated with elevated risk of heart failure ( HF ). Despite poor agreement between automated, administrative code-based HF definitions and physician-adjudicated HF , no studies have evaluated incident adjudicated HF for people living with HIV ( PLWH ). Methods and Results We analyzed PLWH and uninfected controls receiving care in an urban medical system from January 1, 2000, to July 12, 2016. Physicians reviewed data from medical records to adjudicate HF diagnoses. We used multivariable-adjusted Cox models to analyze incident HF for PLWH versus controls and HIV -related factors associated with incident HF . We also analyzed the performance of automated versus physician-adjudicated HF definitions. Incident adjudicated HF occurred in 97 of 4640 PLWH (2.1%; mean: 6.8 years to HF ) and 55 of 4250 controls (1.3%; mean: 6.7 years to HF ; multivariable-adjusted hazard ratio: 2.10; 95% confidence interval, 1.38-3.21). Among PLWH , higher HIV viral load ( hazard ratio per log10 higher time-updated viral load: 1.22; 95% confidence interval, 1.11-1.33) was associated with greater HF risk and higher CD 4+ T cell count was associated with lower HF risk ( hazard ratio per 100 cells/mm3 higher time-updated CD 4 count: 0.80; 95% confidence interval, 0.69-0.92). In exploratory analyses, the most accurate automated HF definitions had sensitivities of 67% to 75% and positive predictive values of 54% to 60%. Conclusions In a cohort with rigorous HF adjudication, PLWH had greater risks of HF than uninfected people after adjustment for demographics and cardiovascular risk factors. Higher HIV viral load and lower CD 4+ T cell count were associated with higher HF risk among PLWH . Automated methods of HF ascertainment exhibited poor accuracy for PLWH and uninfected people.
| S-EPMC6404176 | biostudies-literature
Project description:Objective This study sought to investigate associations between serum total and free 25(OH)D and bacterial vaginosis (BV) in early and later pregnancy among US black women to provide insight into the most clinically relevant measure of vitamin D status among pregnant black women with respect to risk for BV as well as insights into critical time points for measuring and/or addressing vitamin D status in pregnancy. Methods Data and biospecimens were derived from a subsample (N = 137) of women from the Emory University African American Vaginal, Oral, and Gut Microbiome in Pregnancy Cohort, for whom data related to vitamin D status (serum assays for total and free 25(OH)D) and Nugent score of Gram stained vaginal specimens in early (8-14 weeks) and later (24-30 weeks) were available. We compared total and free 25(OH)D concentrations for women according to Nugent score category (normal flora, intermediate flora, and BV) and assessed the odds of BV according to measures of vitamin D status. Results Thirty-seven (27%) women had adequate vitamin D status at baseline, whereas 70 (51%) had insufficient vitamin D and 30 (22%) were vitamin D deficient; there were not significant differences in the proportion of women with adequate, insufficient, or deficient vitamin D according to Nugent score category. However, the odds of BV later in pregnancy were significantly higher for women who experienced a smaller rise in total 25(OH)D and free 25(OH)D from 8-14 through 24-30 weeks gestation. Conclusion The change in measures of vitamin D status from early to later pregnancy is associated with the occurrence of BV in pregnancy. Further research is needed to examine the association between the change in vitamin D status over pregnancy and the occurrence of BV and other measures of vaginal microbial composition as well as to identify factors that influence change in vitamin D status over pregnancy.
| S-EPMC6332941 | biostudies-other
Project description:BackgroundReference values for hematological and biochemical assays in pregnant women and in newborn infants are based primarily on Caucasian populations. Normative data are limited for populations in sub-Saharan Africa, especially comparing women with and without HIV infection, and comparing infants with and without HIV infection or HIV exposure.MethodsWe determined HIV status and selected hematological and biochemical measurements in women at 20-24 weeks and at 36 weeks gestation, and in infants at birth and 4-6 weeks of age. All were recruited within a randomized clinical trial of antibiotics to prevent chorioamnionitis-associated mother-to-child transmission of HIV (HPTN024). We report nearly complete laboratory data on 2,292 HIV-infected and 367 HIV-uninfected pregnant African women who were representative of the public clinics from which the women were recruited. Nearly all the HIV-infected mothers received nevirapine prophylaxis at the time of labor, as did their infants after birth (always within 72 hours of birth, but typically within just a few hours at the four study sites in Malawi (2 sites), Tanzania, and Zambia.ResultsHIV-infected pregnant women had lower red blood cell counts, hemoglobin, hematocrit, and white blood cell counts than HIV-uninfected women. Platelet and monocyte counts were higher among HIV-infected women at both time points. At the 4-6-week visit, HIV-infected infants had lower hemoglobin, hematocrit and white blood cell counts than uninfected infants. Platelet counts were lower in HIV-infected infants than HIV-uninfected infants, both at birth and at 4-6 weeks of age. At 4-6 weeks, HIV-infected infants had higher alanine aminotransferase measures than uninfected infants.ConclusionNormative data in pregnant African women and their newborn infants are needed to guide the large-scale HIV care and treatment programs being scaled up throughout the continent. These laboratory measures will help interpret clinical data and assist in patient monitoring in a sub-Saharan Africa context.
| S-EPMC2746190 | biostudies-literature
Project description:BackgroundIntravaginal practices (IVP) (cleansing or introducing products inside the vagina for hygiene, health or to please sexual partners) are common among women with HIV. IVP increase the risk of developing bacterial Vaginosis (BV), the most common genital infection associated with transmission of sexually transmitted infections and HIV. This study tested a pilot intervention to reduce IVP and BV in HIV infected women in Zambia.MethodsOne hundred twenty-eight HIV infected women engaging in IVP were randomized to two conditions: enhanced standard of care (n = 70) and experimental (n = 58) from May 1, 2013 to February 28, 2014. All participants received a brief educational counseling session on discontinuation of IVP, and those with BV, were provided with medical treatment for BV. Women in the experimental condition received an additional group-based, culturally tailored intervention. Participants completed questionnaires assessing sexual risk factors and IVP and were assessed for BV using Nugent criteria at baseline, 6 months and 12 months.ResultsAt 12-month, the proportion of self-reported use of IVPs decreased in the experimental condition: soap (28% vs. 47%); cloth or a rag (19% vs. 38%); and traditional medicines (22% vs. 42%) (all p < 0.05)) compared with the enhanced standard of care condition. The prevalence of BV at 6 and 12 months did not differ by study condition but averaging over study condition, prevalence of BV decreased from 64.2% at baseline to 15.6% at 6 months (p < 0.01) and to 23.6% at 12 months (p = 0.15). Using an enhanced standard of care approach and an enhanced standard of care + a group intervention, IVP and BV decreased over time, but the experimental condition had greater reduction in self-reported use of IVP.ConclusionsFuture studies should address interventions in communities with high burden of IVP, BV and HIV. Interventions that could be administered during routine medical care and decrease IVP and BV are needed, and should be considered part of women's health programs.Trial registration numberNCT03134924 (retrospectively registered 21st April 2017).
| S-EPMC5427559 | biostudies-literature
Project description:Dual method use, use of condoms plus another effective contraceptive method, is important in settings with high rates of unintended pregnancy and HIV infection. We evaluated the association of HIV status with dual method use in a cohort of postpartum women. Women completed baseline surveys in the postpartum ward and telephone surveys about contraceptive use 3, 6, and 12 months later. Nonpregnant women who completed at least one follow-up survey were eligible for this secondary analysis. Prevalence ratios were calculated using generalized estimating equations. Of the 511 sexually active women who completed a follow-up survey, condom use increased from 17.6% to 27.7% and nonbarrier contraceptive use increased from 73.8% to 87.6% from 3 to 12 months after delivery. Dual method use increased from 1.0% to 18.9% at 3 to 12 months after delivery. Dual method use was negligible and comparable between HIV-infected and HIV-uninfected women at 3 months but significantly higher among HIV-infected women at 6 months (APR = 3.9, 95% CI 2.2, 7.1) and 12 months (APR = 2.7, 95% CI 1.7, 4.3). Dual method use was low but largely driven by condom use among HIV-infected women at 6 and 12 months after delivery.
| S-EPMC5540462 | biostudies-other