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Toll-like receptor gene variants associated with bacterial vaginosis among HIV-1 infected adolescents.

ABSTRACT: 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.

SUBMITTER: Royse KE

PROVIDER: S-EPMC3518650 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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Toll-like receptor gene variants associated with bacterial vaginosis among HIV-1 infected adolescents.

Royse Kathryn E KE Kempf Mirjam-Colette MC McGwin Gerald G Wilson Craig M CM Tang Jianming J Shrestha Sadeep S

Journal of reproductive immunology 20120928 1-2

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 (TL ...[more]

PMID: 23021866

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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.

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).

Dataset Information

Toll-like receptor gene variants associated with bacterial vaginosis among HIV-1 infected adolescents.

Publications

Toll-like receptor gene variants associated with bacterial vaginosis among HIV-1 infected adolescents.

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