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Defining characteristics of genital health in South African adolescent girls and young women at high risk for HIV infection.

ABSTRACT: The genital tract of African women has been shown to differ from what is currently accepted as 'normal', defined by a pH?4.5 and lactobacilli-dominated microbiota. Adolescent girls and young women (AGYW) from sub-Saharan Africa are at high risk for HIV, and we hypothesized that specific biological factors are likely to be influential. This study aimed to compare characteristics of vaginal health in HIV-negative AGYW (16-22-years-old), from two South African communities, to international norms. We measured plasma hormones, vaginal pH, presence of BV (Nugent scoring), sexually transmitted infections (multiplex PCR for Chlamydia trachomatis, Neisseria gonorrhoea, Trichomonas vaginalis, Mycoplasma genitalium) and candidiasis (Gram stain) in AGYW (n = 298) from Cape Town and Soweto. Cervicovaginal microbiota was determined by 16S pyrosequencing; 44 genital cytokines were measured by Luminex; and cervical T-cell activation/proliferation (CCR5, HLA-DR, CD38, Ki67) was measured by multiparametric flow cytometry. 90/298 (30.2%) AGYW were negative for BV, candidiasis and bacterial STIs. L. crispatus and L. iners were the dominant bacteria in cervicovaginal swabs, and the median vaginal pH was 4.7. AGYW with L. crispatus-dominant microbiota (42.4%) generally had the lowest cytokine concentrations compared to women with more diverse microbiota (34/44 significantly upregulated cytokines). Frequencies of CCR5+CD4+ T-cells co-expressing CD38 and HLA-DR correlated positively with interleukin (IL)-6, TNF-?, GRO-?, macrophage inflammatory protein (MIP)-1?, and IL-9. While endogenous oestrogen had an immune-dampening effect on IL-6, TNF-related apoptosis-inducing ligand (TRAIL) and IL-16, injectable hormone contraceptives (DMPA and Net-EN) were associated with significantly lower endogenous hormone concentrations (p<0.0001 for oestrogen and progesterone) and upregulation of 34/44 cytokines. Since genital inflammation and the presence of activated CD4+ T cells in the genital tract have been implicated in increased HIV risk in South African women, the observed high levels of genital cellular activation and cytokines from AGYW may point towards biological factors increasing HIV risk in this region.

SUBMITTER: Dabee S

PROVIDER: S-EPMC6448899 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Project description:ImportanceIn South Africa, adolescent girls and young women aged 15 to 24 years are among the most high-risk groups for acquiring HIV. Progress in reducing HIV incidence in this population has been slow.ObjectiveTo describe HIV prevalence and HIV risk behaviors among a sample of adolescent girls and young women and to model the association between exposure to multiple or layered interventions and key HIV biological and behavioral outcomes.Design, setting, and participantsThis cross-sectional survey was conducted between March 13, 2017, and June 22, 2018, in 2 districts in Gauteng province and in 2 districts in KwaZulu-Natal province in South Africa. A stratified cluster random sampling method was used. Participants included adolescent girls and young women aged 12 to 24 years who lived in each sampled household. Overall, 10 384 participants were enrolled in Gauteng province and 7912 in KwaZulu-Natal province. One parent or caregiver was interviewed in each household. Data analysis was performed from March 12, 2021, to March 1, 2022.ExposuresDREAMS (Determined, Resilient, Empowered, AIDS-free, Mentored, and Safe)-like interventions.Main outcomes and measuresThe primary outcome was HIV prevalence. HIV status was obtained from laboratory-based testing of peripheral blood samples. Secondary outcomes included HIV testing and antiretroviral therapy uptake as well as numerous HIV risk variables that the DREAMS program sought to improve, such as pregnancy, sexually transmitted infection, intimate partner violence, and age-disparate sex.ResultsThe final sample included 18 296 adolescent girls and young women (median [IQR] age, 19 [15-21] years) in 10 642 households. Approximately half of participants (49.9%; n = 8414) reported engaging in sexual activity, and 48.1% (n = 3946) reported condom use at the most recent sexual encounter. KwaZulu-Natal province had a higher HIV prevalence than Gauteng province (15.1% vs 7.8%; P < .001). Approximately one-fifth of participants (17.6%; n = 3291) were not exposed to any interventions, whereas 43.7% (n = 8144) were exposed to 3 or more interventions. There was no association between exposure to DREAMS-like interventions and HIV status. Adolescent girls and young women who accessed 3 or more interventions were more likely to have undergone HIV testing (adjusted odds ratio, 2.39; 95% CI, 2.11-2.71; P < .001) and to have used condoms consistently in the previous 12 months (adjusted odds ratio, 1.68; 95% CI, 1.33-2.12; P < .001) than those who were not exposed to any interventions.Conclusions and relevanceResults of this study suggest that self-reported exposures to multiple or layered DREAMS-like interventions were associated with favorable behavioral outcomes. The beneficial aspects of layering HIV interventions warrant further research to support the sexual and reproductive health of adolescent girls and young women.

Project description:BackgroundFemale genital tract (FGT) inflammation is an important risk factor for HIV acquisition. The FGT microbiome is closely associated with inflammatory profile; however, the relative importance of microbial activities has not been established. Since proteins are key elements representing actual microbial functions, this study utilized metaproteomics to evaluate the relationship between FGT microbial function and inflammation in 113 young and adolescent South African women at high risk of HIV infection. Women were grouped as having low, medium, or high FGT inflammation by K-means clustering according to pro-inflammatory cytokine concentrations.ResultsA total of 3186 microbial and human proteins were identified in lateral vaginal wall swabs using liquid chromatography-tandem mass spectrometry, while 94 microbial taxa were included in the taxonomic analysis. Both metaproteomics and 16S rRNA gene sequencing analyses showed increased non-optimal bacteria and decreased lactobacilli in women with FGT inflammatory profiles. However, differences in the predicted relative abundance of most bacteria were observed between 16S rRNA gene sequencing and metaproteomics analyses. Bacterial protein functional annotations (gene ontology) predicted inflammatory cytokine profiles more accurately than bacterial relative abundance determined by 16S rRNA gene sequence analysis, as well as functional predictions based on 16S rRNA gene sequence data (p < 0.0001). The majority of microbial biological processes were underrepresented in women with high inflammation compared to those with low inflammation, including a Lactobacillus-associated signature of reduced cell wall organization and peptidoglycan biosynthesis. This signature remained associated with high FGT inflammation in a subset of 74 women 9 weeks later, was upheld after adjusting for Lactobacillus relative abundance, and was associated with in vitro inflammatory cytokine responses to Lactobacillus isolates from the same women. Reduced cell wall organization and peptidoglycan biosynthesis were also associated with high FGT inflammation in an independent sample of ten women.ConclusionsBoth the presence of specific microbial taxa in the FGT and their properties and activities are critical determinants of FGT inflammation. Our findings support those of previous studies suggesting that peptidoglycan is directly immunosuppressive, and identify a possible avenue for biotherapeutic development to reduce inflammation in the FGT. To facilitate further investigations of microbial activities, we have developed the FGT-DB application that is available at http://fgtdb.org/ . Video Abstract.

Project description:BACKGROUND:Evidence on the role of age-disparate partnerships in high HIV-infection rates among young women in sub-Saharan Africa remains inconclusive. This study examined the HIV-infection risk associated with age-disparate partnerships among 15- to 24-year-old women in a hyperendemic setting in South Africa. METHODS:Face-to-face questionnaire, and laboratory HIV and viral load data were collected during 2014-2015 among a representative sample (15-49 years old) in KwaZulu-Natal. The association between age-disparate partnerships (age difference ≥5 years) and HIV status among 15- to 24-year-old women (N = 1459) was assessed using multiple logistic regression analyses. Data from the male sample on all on-going partnerships (N = 1229) involving 15- to 24-year-old women were used to assess whether young women's age-disparate male partners were more likely to have a viral load ≥1000 copies per milliliter, a marker of HIV-infection risk. RESULTS:Women reporting an age disparity in any of their 3 most recent partnerships were more likely to test HIV positive compared to women with only age-similar partners [adjusted odds ratio (aOR): 1.58, 95% confidence interval (CI): 1.20 to 2.09, P < 0.01]. Among partnerships men reported with 15- to 24-year-old women, the age-disparate male partners were more likely to be HIV positive and have a viral load ≥1000 copies per milliliter (aOR: 2.05, 95% CI: 1.30 to 3.24, P < 0.01) compared with age-similar partners. Results were similar for each category of age disparity: partners 5-9 years older (aOR: 2.01, 95% CI: 1.18 to 3.43, P = 0.010) and those ≥10 years older (aOR: 2.17, 95% CI: 1.01-4.66, P = 0.048). CONCLUSIONS:Results indicate that age-disparate partnerships increase young women's HIV risk, although conclusive evidence was not ascertained. Interventions addressing risk from age-disparate sexual partnering, including expanding antiretroviral treatment among older partners, may help to reduce HIV incidence among young women.

Project description:OBJECTIVE:There is an urgent need to understand high HIV-infection rates among young women in sub-Saharan Africa. While age-disparate partnerships have been characterised with high-risk sexual behaviours, the mechanisms through which these partnerships may increase HIV-risk are not fully understood. This study assessed the association between age-disparate partnerships and herpes simplex virus type-2 (HSV-2) infection, a factor known to increase HIV-infection risk. METHODS:Cross-sectional face-to-face questionnaire data, and laboratory HSV-2 and HIV antibody data were collected among a representative sample in the 2014/2015 household survey of the HIV Incidence Provincial Surveillance System in KwaZulu-Natal, South Africa. Among 15-24-year-old women who reported having ever had sex (n=1550), the association between age-disparate partnerships (ie, male partner ≥5 years older) and HSV-2 antibody status was assessed using multivariable Poisson regression models with robust variance. Analyses were repeated among HIV-negative women. RESULTS:HSV-2 prevalence was 55% among 15-24-year-old women. Women who reported an age-disparate partnership with their most recent partner were more likely to test HSV-2 positive compared with women with age-similar partners (64% vs 51%; adjusted prevalence ratio (aPR):1.19 (95% CI 1.07 to 1.32, p<0.01)). HSV-2 prevalence was also significantly higher among HIV-negative women who reported age-disparate partnerships (51% vs 40 %; aPR:1.25 (95% CI 1.05 to 1.50, p=0.014)). CONCLUSIONS:Results indicate that age-disparate partnerships are associated with a greater risk of HSV-2 among young women. These findings point towards an additional mechanism through which age-disparate partnerships could increase HIV-infection risk. Importantly, by increasing the HSV-2 risk, age-disparate partnerships have the potential to increase the HIV-infection risk within subsequent partnerships, regardless of the partner age-difference in those relationships.

Project description:In sub-Saharan Africa, high HIV incidence rates in adolescent girls and young women (AGYW) persist despite extensive HIV prevention efforts. A prospective cohort of 2,710 HIV-negative AGYW (15-24 years) in KwaZulu-Natal, South Africa were interviewed at baseline and followed-up approximately 18 months later (2014-2017). Associations between HIV seroconversion and socio-demographic and behavioural variables measured at baseline and follow-up were examined using Cox regression and a proximate determinants framework. Inter-relationships between determinants were measured using logistic regression. Separate models were built for 15-19 and 20-24-year-olds. Weighted HIV incidence was 3.92 per 100 person-years (95% confidence interval: 3.27-4.69; 163 seroconversions over 4,016 person-years). Among 15-19-year-olds, absence of family support (adjusted hazards ratio (aHR): 3.82 (1.89-7.72)), having a circumcised partner (aHR: 0.5 (0.27-0.94)) or one who was HIV-positive and not on antiretroviral therapy (ART) (aHR: 6.21 (2.56-15.06)) were associated with HIV incidence. Those reporting an absence of family support were also more likely to report >1 partner during follow-up (odds ratio (OR): 2.7(1.11-6.57)). Among 20-24-year-olds, failure to complete secondary school (aHR: 1.89 (1.11-3.21)), inconsistent condom use (aHR: 3.01 (1.14-7.96)) and reporting partner(s) who were HIV-positive and not on ART (aHR: 7.75 (3.06-19.66)) were associated with HIV incidence. Failure to complete secondary school among 20-24-year-olds was associated with inconsistent condom use (OR: 1.82 (1.20-2.77)) and reporting an HIV-positive partner not on ART (OR: 3.53(1.59-7.82)) or an uncircumcised partner (OR: 1.39 (1.08-1.82). Absence of family support and incomplete schooling are associated with risky sexual behaviours and HIV acquisition in AGYW. In addition, partner-level prevention-condom use, medical circumcision, and viral suppression-continue to play an important role in reducing HIV risk in AGYW. These findings support the use of combination HIV prevention programs that consider structural as well as biological and behavioural HIV risk factors in their design.

Project description:BackgroundSouth African adolescent girls and young women (AGYW) report significant mental distress and sexual and reproductive health concerns. Mental health problems and trauma symptoms are consistently associated with sexual and reproductive health behavior. Despite their intersection, few interventions address them simultaneously or engage female caregivers (FC) as collaborators. This study presents findings from a pilot test of an empirically supported culturally adapted family-based HIV-prevention program, Informed Motivated Aware and Responsible Adolescents and Adults- South Africa (IMARA-SA), on AGYW anxiety, depression, and trauma.MethodsSixty 15-19-year-old AGYW (mean age = 17.1 years) and their FC from outside Cape Town were randomized to IMARA-SA or a health promotion control program. AGYW reported their anxiety using the GAD-7, depression using the PHQ-9, and trauma using the PC-PTSD-5 at baseline and follow-up (6-10 months post). Both interventions were delivered by Xhosa-speaking Black South African women in groups over 2 days for approximately 10 h. We examined intervention effects using zero-inflated negative binomial regression for anxiety, multinomial logistic regression for depression, and logistic regression for trauma.ResultsAt baseline, groups did not differ in demographic characteristics but AGYW randomized to IMARA-SA had higher depression scores than controls (p = 0.04) and a greater proportion screened positive for PTSD (p = .07). Controlling for baseline mental health scores, AGYW who received IMARA-SA compared to controls had significantly fewer anxiety symptoms at follow-up (adjusted incidence rate ratio for count model = 0.54, 95% CI = 0.29-0.99, p = 0.05), were less likely to report at least one depressive symptom relative to no symptoms (relative risk ratio = 0.22, 95% CI = 0.05, 0.95, p = 0.04), and were less likely to report symptoms of PTSD relative to no symptoms, but this difference was not statistically significant.ConclusionsMental health is implicated in risky sexual behavior, and reducing emotional distress can mitigate exposure to poor sexual and reproductive health outcomes. This pilot study yielded promising findings for the mental health impact of IMARA-SA, justifying replication in a larger randomized trial.Trial registrationClinicalTrials.gov Number NCT04758390 , accepted 17/02/2021.

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Defining characteristics of genital health in South African adolescent girls and young women at high risk for HIV infection.

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