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Background Preexposure prophylaxis (PrEP) programs present a platform for diagnostic sexually transmitted infection (STI) testing in low- and middle-income countries, and availability of targeted STI testing has been hypothesized to influence PrEP use. We evaluated the association of STI testing modality and PrEP uptake among pregnant women in antenatal care. Methods We enrolled pregnant, HIV-uninfected women (16 years or older) at their first antenatal visit with follow-up through 12 months postpartum. Women were offered oral PrEP and tested for Chlamydia trachomatis and Neisseria gonorrhoeae using a point-of-care (POC; Cepheid, August 2019-November 2020) or laboratory-based (Thermofisher, December 2020-October 2021) test. We compared the proportion of women initiating and continuing PrEP by STI test adjusting for confounders. Results We evaluated 1194 women (median age, 26 years [interquartile range, 22-31 years]) with an STI result (46% POC and 54% laboratory-based). The prevalence of any STI was the same in POC-tested (28%) and laboratory-tested (28%) women - 25% versus 23% for C. trachomatis (P = 0.35) and 7% versus 9% for N. gonorrhoeae (P = 0.11). Mean time from testing to result was 0 day for POC and 26 days for laboratory testing, and mean time from testing to treatment was 3 days for POC and 38 days for laboratory testing. Receiving a POC STI test was associated with higher PrEP initiation compared with women receiving a laboratory-based test (90% vs. 78%; adjusted odds ratio, 2.1; 95% confidence interval, 1.5-2.9), controlling for age, gravidity, STI diagnosis, intimate partner violence, gestational age, employment, HIV risk perception, and cohabiting status. Conclusions Point-of-care STI testing, offering same-day results and treatment initiation, may increase PrEP initiation among pregnant women in antenatal care.

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.

Purpose of review: Women in Africa bear the burden of the HIV epidemic, which has been associated with the high prevalence of bacterial vaginosis (BV) in the region. However, little progress has been made in finding an effective cure for BV. Drawing on advances in microbiome-directed therapies for gastrointestinal disorders, similar live-biotherapeutic based approaches for BV treatment are being evaluated. Here, we summarize current knowledge regarding vaginal microbiota in BV, explore geographical differences in vaginal microbiota, and argue that novel BV therapeutics should be tailored specifically to meet the needs of African women. Recent findings: Cervicovaginal microbiota dominated by Lactobacillus crispatus are optimal, although these are uncommon in African women. Besides socio-behavioural and environmental influences on the vaginal microbiota, host and microbial genetic traits should be considered, particularly those relating to glycogen metabolism. Novel microbiome-directed approaches being developed to treat BV should employ transfers of multiple microbial strains to ensure sustained colonization and BV cure. Summary: Improving the efficacy and durability of BV treatment with microbiome-directed therapies by appropriately accounting for host and microbial genetic factors, could potentially reduce the risk of HIV infection in African women. [ABSTRACT FROM AUTHOR]

Previous studies on the differences in gut microbiota between exclusively breastfed (EBF) and non-EBF infants have provided highly variable results. Here we perform a meta-analysis of seven microbiome studies (1825 stool samples from 684 infants) to compare the gut microbiota of non-EBF and EBF infants across populations. In the first 6 months of life, gut bacterial diversity, microbiota age, relative abundances of Bacteroidetes and Firmicutes, and predicted microbial pathways related to carbohydrate metabolism are consistently higher in non-EBF than in EBF infants, whereas relative abundances of pathways related to lipid metabolism, vitamin metabolism, and detoxification are lower. Variation in predicted microbial pathways associated with non-EBF infants is larger among infants born by Caesarian section than among those vaginally delivered. Longer duration of exclusive breastfeeding is associated with reduced diarrhea-related gut microbiota dysbiosis. Furthermore, differences in gut microbiota between EBF and non-EBF infants persist after 6 months of age. Our findings elucidate some mechanisms of short and long-term benefits of exclusive breastfeeding across different populations.

BackgroundExclusive breastfeeding reduces the rate of postnatal human immunodeficiency virus (HIV) transmission compared to nonexclusive breastfeeding; however, the mechanisms of this protection are unknown. Our study aimed to interrogate the mechanisms underlying the protective effect of exclusive breastfeeding.MethodsWe performed a prospective, longitudinal study of infants from a high-HIV-prevalence, low-income setting in South Africa. We evaluated the role of any non-breast milk feeds, excluding prescribed medicines on stool microbial communities via 16S rRNA gene sequencing, peripheral T-cell activation via flow cytometry, and buccal mucosal gene expression via quantitative polymerase chain reaction assay.ResultsA total of 155 infants were recruited at birth with mean gestational age of 38.9 weeks and mean birth weight of 3.2 kg. All infants were exclusively breastfed (EBF) at birth, but only 43.5% and 20% remained EBF at 6 or 14 weeks of age, respectively. We observed lower stool microbial diversity and distinct microbial composition in exclusively breastfed infants. These microbial communities, and the relative abundance of key taxa, were correlated with peripheral CD4+ T-cell activation, which was lower in EBF infants. In the oral mucosa, gene expression of chemokine and chemokine receptors involved in recruitment of HIV target cells to tissues, as well as epithelial cytoskeletal proteins, was lower in EBF infants.ConclusionsThese data suggest that nonexclusive breastfeeding alters the gut microbiota, increasing T-cell activation and, potentially, mucosal recruitment of HIV target cells. Study findings highlight a biologically plausible mechanistic explanation for the reduced postnatal HIV transmission observed in EBF infants.

Determinants of the acquisition and maintenance of maternal microchimerism (MMc) during infancy and the impact of MMc on infant immune responses are unknown. We examined factors that influence MMc detection and level across infancy and the effect of MMc on T cell responses to bacillus Calmette-Guerin (BCG) vaccination in a cohort of HIVexposed, uninfected and HIV-unexposed infants in South Africa. MMc was measured in whole blood from 58 infants using a panel of quantitative PCR assays at day 1, and 7, 15, and 36 weeks of life. Infants received BCG at birth, and selected whole blood samples from infancy were stimulated in vitro with BCG and assessed for polyfunctional [CD4.sup.+] T cell responses. MMc was present in most infants across infancy, with levels ranging from 0 to 1,193/100,000 genomic equivalents and was positively impacted by absence of maternal HIV, maternal and infant HLA compatibility, infant female sex, and exclusive breastfeeding. Initiation of maternal antiretroviral therapy prior to pregnancy partially restored MMc level in HIV-exposed, uninfected infants. Birth MMc was associated with an improved polyfunctional [CD4.sup.+] T cell response to BCG. These data emphasize that both maternal and infant factors influence the level of MMc, which may subsequently affect infant T cell responses., Introduction During pregnancy maternal cells are transferred to the fetus and persist in small quantities postnatally, a phenomenon known as maternal microchimerism (MMc). The impact of these maternal cells on [...]

Reporting bias in adolescent behavioural research may be overcome with the use of personal digital assistants (PDA) or other computer based technologies. However, there is little insight into the use of these tools among adolescents in low resource settings. We compared self-administered paper questionnaires with PDA questionnaires to collect sexual behaviour data from a sample of 11-19 year olds living in a periurban, Xhosa-speaking community in South Africa. There was a high level of agreement between sexual risk behaviour data collected via each method (kappas greater than or equal to 0.50). Data collected from the PDA questionnaires were more complete. Subjectively, adolescents found the use of PDA to be simple and confidential. PDA may be a useful method to collect sensitive, self-reported information from adolescents in resource-limited settings.

Cesarean section rates continue to rise globally, and C-sectioned infants are at a higher risk of adverse child outcomes. In this issue of Cell Host & Microbe , Zhou et al. report that vaginal microbial transfer (VMT) from birth mother to infant post-delivery may alter infant gut microbiota and improve neurodevelopment. [ABSTRACT FROM AUTHOR]