Young women in sub-Saharan Africa are disproportionally affected by HIV infection and unintended pregnancies. However, hormonal contraceptive (HC) use may influence HIV risk through changes in genital tract microbiota and inflammatory cytokines. To investigate this, 130 HIV negative adolescent females aged 15–19 years were enrolled into a substudy of UChoose, an open-label randomized crossover study (NCT02404038), comparing acceptability and contraceptive product preference as a proxy for HIV prevention delivery methods. Participants were randomized to injectable norethisterone enanthate (Net-En), combined oral contraceptives (COC) or etonorgesterol/ethinyl estradiol combined contraceptive vaginal ring (CCVR) for 16 weeks, then crossed over to another HC for 16 weeks. Cervicovaginal samples were collected at baseline, crossover and exit for characterization of the microbiota and measurement of cytokine levels; primary endpoints were cervical T cell activation, vaginal microbial diversity and cytokine concentrations. Adolescents randomized to COCs had lower vaginal microbial diversity and relative abundance of HIV risk-associated taxa compared to Net-En or CCVR. Cervicovaginal inflammatory cytokine concentrations were significantly higher in adolescents randomized to CCVR compared to COC and Net-En. This suggests that COC use may induce an optimal vaginal ecosystem by decreasing bacterial diversity and inflammatory taxa, while CCVR use is associated with genital inflammation.

Introduction: Young women in Southern Africa have extremely high HIV incidence rates necessitating the availability of female-controlled prevention methods. Understanding adolescent preference for seeking contraception would improve our understanding of acceptability, feasibility and adherence to similar modes of delivery for HIV prevention. Methods: UChoose was an open-label randomized crossover study over 32 weeks which aimed to evaluate the acceptability and preference for contraceptive options in healthy, HIV-uninfected, female adolescents aged 15 to 19 years, as a proxy for similar HIV prevention methods. Participants were assigned to a contraceptive method for a period of 16 weeks in the form of a bimonthly injectable contraceptive, monthly vaginal Nuvaring â or daily combined oral contraceptive (COC) and then asked to state their preference. At 16 weeks, participants crossed over to another contraceptive method, to ensure that all participants tried the Nuvaring â (least familiar modality) and additionally, either the injection or COC. Primary outcomes were contraceptive acceptability and preference. At the end of the 32 weeks they were also asked to imagine their preference for an HIV prevention modality. Secondary endpoints included changes in sexual behaviour, contraceptive adherence and preference for biomedical and behavioural HIV prevention methods. Results: Of the 180 participants screened, 130 were enrolled and randomized to the Nuvaring â (n = 45), injection (n = 45) or COC (n = 40). Significantly more Nuvaring â users (24/116; 20.7%) requested to change to another contraceptive option compared to injection (1/73; 1.4% p = 0.0002) and COC users (4/49; 8% p = 0.074). Of those that remained on the Nuvaring â , adherence was significantly higher than to COC (p < 0.0001). Significantly more injection users (77/80; 96.3%) thought this delivery mode was convenient to use compared to Nuvaring â (74/89; 83.1%; p = 0.0409) or COC (38/50; 76.0%; p = 0.0034). Overall, the preferred contraceptive choice was injection, followed by the ring and lastly the pill. Conclusions: Adherence to daily COC was difficult for adolescents in this cohort and the least favoured potential HIV prevention option. While some preferred vaginal ring use, these data suggest that long-acting injectables would be the preferred prevention method for adolescent girls and young women. This study highlights the need for additional options for HIV prevention in youth.

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Background Adolescents in sub-Saharan Africa are at risk for HIV infection and unintended pregnancies. Observational studies suggest that injectable hormonal contraceptives (HC) increase HIV risk, although their effects on genital inflammation, particularly HIV-susceptible Th17 cells, are unknown. In a randomized cross-over study, the effect of injectable norethisterone oenanthate (NET-EN), combined contraceptive vaginal rings (CCVR; NuvaRing®), and combined oral contraceptive pills (COCPs) on cervical Th17 cells and cytokines were compared. Methods Adolescents (n=130; 15-19 years), randomized 1:1:1 to NET-EN, CCVR, or COCPs for 16-weeks, subsequently crossed-over to another HC for 16-weeks. Estrogen (E2), follicular stimulating hormone (FSH), and luteinizing hormone (LH) were measured. CCR5, HLA-DR and CD38 expression by cervical cytobrush-derived CD4+ T cells was assessed by FACS. Th17 cells were defined as CCR6+CCR10-. Cervicovaginal Th17-related cytokines were measured by Luminex. Results CCVR use for the first 16-weeks was associated with reduced Th17 frequencies and lower FHS and LH concentrations compared to NET-EN/COCPs, with FHS concentrations and Th17 frequencies correlating significantly. However, Th17-related cytokine concentrations (IL-21, IL-1β, TNF-α, IFN-γ) and CCR5+HLA-DR+CD38+ Th17 frequencies were significantly higher in CCVR than NET-EN/COCP. At cross-over, CCVR users changing to COCPs or NET-EN did not resolve activation or cytokines, although switching from COCP to CCVRs increased cytokine concentrations. Conclusion CCVR use altered endogenous hormone levels and associated cervical Th17 cell frequencies to greater extent than NET-EN/COCPs, although Th17 cells were more activated and Th17-related cytokine concentrations were elevated. While CCVRs may impact HIV risk by regulating Th17 numbers, increased activation/inflammation may balance any risk gains.

Bacterial vaginosis (BV) and periodontal disease (PD) are characterised as bacterial dysbioses. Both are associated with an increased risk of poor pregnancy outcomes, yet it is unknown whether PD and BV are related. We characterised the oral microbiota of young South African females with a high prevalence of BV and investigated the association between oral communities and vaginal microbiota. DNA was extracted from vaginal lateral wall, saliva and supragingival plaque samples from 94 adolescent females (aged 15–19 years). 16S rRNA gene sequencing of the V4 hypervariable region was performed for analysis of the oral and vaginal microbiota and BV status was determined by Nugent scoring. The core oral microbiota was predominately comprised of Firmicutes followed by Proteobacteria and Bacteroidetes. The salivary microbiota of participants with BV was more diverse than those with lactobacillus-dominated communities (p = 0.030). PD-associated bacterial species, including Prevotella intermedia and Porphyromonas endodontalis were enriched in the supragingival microbiota of women with non-optimal vaginal communities compared to those with Lactobacillus-dominant communities, while Pseudomonas aeruginosaand Prevotella intermedia were enriched in the saliva of women with non-optimal vaginal microbiota. These data suggest a relationship between oral and vaginal dysbiosis, warranting further investigation into whether they are casually related.

ObjectivesYoung women in sub-Saharan Africa are at high risk of STIs and unintended pregnancies, yet hormonal contraceptive (HC) use may affect STI risk. We compared the influence of three HCs on the incidence and prevalence of STIs and bacterial vaginosis (BV) in South African adolescents.MethodsOne hundred and thirty adolescents between 15 and 19 years were randomised to the injectable norethisterone enanthate (Net-En), combined oral contraceptives (COC) (Triphasil or Nordette) or a combined contraceptive vaginal ring (CCVR; NuvaRing) for 16 weeks (clinicaltrials.gov/NCT02404038). Vaginal samples were collected at baseline and 16 weeks post contraceptive initiation for STI and BV testing.ResultsIn an intention-to-treat analysis, no significant differences in BV prevalence were found between study arms. The overall incidence of any STI at follow-up was high: 16.2% in the COC arm; 25.7% in the Net-En arm; and 37.1% in the CCVR arm. The incidence rate (IR) of any STI was similar between Net-En (IR 0.74 (95% CI 0.34 to 1.41)) and the oestrogen-containing contraceptives (IR 0.78 (95% CI 0.47 to 1.22)). A lower IR of Chlamydia trachomatis (incidence rate ratio (IRR) 0.68 (95% CI 0.19 to 1.99)) and Neisseria gonorrhoeae (IRR 0.25 (95% CI 0.01 to 1.35)) but a higher IR of Mycoplasma genitalium (IRR 16.0 (95% CI 2.96 to 400)), was observed in the Net-En arm compared with the oestrogen-containing contraceptives, although the overall incidence of M. genitalium was low (4.7%). In an exploratory analysis, the risk of any STI and N. gonorrhoeae was lower in the COC arm compared with CCVR. A per-protocol analysis yielded similar results.ConclusionOur results suggest that use of Net-En may be associated with increased risk of M. genitalium compared with oestrogen-containing contraceptives but not with overall STI risk. COC use may decrease STI risk relative to CCVR.

BackgroundProbiotics are widely used to improve gastrointestinal (GI) health, but they may also be useful to prevent or treat gynaecological disorders, including bacterial vaginosis (BV) and candidiasis. BV prevalence is high in South Africa and is associated with increased HIV risk and pregnancy complications. We aimed to assess the availability of probiotics for vaginal health in retail stores (pharmacies, supermarkets and health stores) in two major cities in South Africa.MethodsA two-stage cluster sampling strategy was used in the Durban and Cape Town metropoles. Instructions for use, microbial composition, dose, storage and manufacturers’ details were recorded.ResultsA total of 104 unique probiotics were identified in Cape Town and Durban (66.4% manufactured locally). Cape Town had more products than Durban (94 versus 59 probiotics), although 47% were common between cities (49/104). Only four products were explicitly for vaginal health. The remainder were for GI health in adults (51.0%) or infants (17.3%). The predominant species seen overall included Lactobacillus acidophilus (53.5%), L. rhamnosus (37.6%), Bifidobacterium longum ssp. longum (35.6%) and B. animalis ssp. lactis (33.7%). Products for vaginal health contained only common GI probiotic species, with a combination of L. acidophilus/B. longum ssp. longum/B. bifidum, L. rhamnosus/L. reuteri or L. rhamnosus alone, despite L. crispatus, L. gasseri, and L. jensenii being the most common commensals found in the lower female reproductive tract.ConclusionThis survey highlights the paucity of vaginal probiotics available in South Africa, where vaginal dysbiosis is common. Most vaginal products contained organisms other than female genital tract commensals.Electronic supplementary materialThe online version of this article (doi:10.1186/s12905-017-0362-6) contains supplementary material, which is available to authorized users.

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