Biology subjects

Yotebieng, M.

Publications and source records attributed to Yotebieng, M..

6 recordsLinked to original sources

bioRxiv2026

Compartment-specific soluble immune profiles associated with preterm birth, perinatal death, and low birthweight in pregnant individuals living with HIV

BackgroundHuman immunodeficiency virus (HIV) infection in pregnancy is associated with preterm birth (PTB), low birthweight (LBW), and perinatal death (PND). Although antiretroviral therapy (ART) suppresses viral load it does not prevent HIV-associated adverse pregnancy outcomes or resolve inflammation. As circulating maternal immune factors may not fully capture maternal-fetal interface immune dysregulation, this observational cohort study aimed to identify localized and systemic immune factors associated with PTB, LBW and PND in ART-treated pregnant people living with HIV (PPLWH). MethodsWe enrolled 118 PPLWH in Kinshasa, Democratic Republic of the Congo, during the second or third trimester. We collected maternal peripheral plasma (at enrollment, 1-3 days post-delivery, and postpartum) alongside umbilical cord and placental plasma at delivery. Concentrations of 45 immune factors were measured via LegendPlex and ELISAs and associations analyzed using Kruskal-Wallis tests with Dunns correction or Mann-Whitney tests. ResultsPlacental plasma exhibited the highest overall concentrations of immune factors, highlighting a distinct localized microenvironment. Among 118 pregnancies, 35 (30%) resulted in PTB, 10 (9%) in PND, and 9 (8%) in LBW. Compared to term births, PTB was associated with higher levels of the chemokines CCL20, CXCL9, and CXCL10 in cord and/or postdelivery plasma (p<0.01), while placental CCL20 levels were lower (p<0.05). Compared to live births, PND was associated with higher postdelivery CXCL1, cord IL-8, placental MPO and NGAL (p<0.05); higher postdelivery CXCL5 (p<0.01); and higher S100A8/A9 levels in cord and postdelivery plasma (p<0.01 and p<0.001, respectively). Finally, LBW was associated with higher enrollment IL-18 and S100A8/A9 levels (p<0.05 and p<0.01, respectively); as well as higher SAA levels in postdelivery and postpartum plasma (p<0.05). ConclusionsIn ART-treated PPLWH, distinct adverse birth outcomes are driven by time- and compartment-specific immune pathways. PTB is associated with localized T-cell chemokine responses, PND with neutrophil recruitment and activation, and LBW with pro-inflammatory cytokine and acute-phase protein responses. These pathways provide mechanistic insights into pregnancy complications in PPLWH and highlight potential compartment-specific biomarkers for risk stratification.

microbiology↗

bioRxiv2025

The cervicovaginal microbiome of pregnant people living with HIV on antiretroviral therapy in the Democratic Republic of Congo: A Pilot Study and Global Meta-analysis.

Recent studies are revealing that a suboptimal cervicovaginal microbiome (CVMB), including enrichment of anaerobic bacteria associated with multiple female genital disorders, and adverse pregnancy and birth outcomes in pregnant people. Problematically, however, the majority of the available data to date are biased towards highly developed, Global North countries, leaving underrepresented populations like the Democratic Republic of Congo (DRC) poorly characterised. Here, we investigate the CVMB from a cohort of 82 pregnant people living with HIV (PLWH) on antiretroviral therapy (ART) from the DRC. Specifically, we explore the associations between the CVMB via 16S rRNA gene sequencing and maternal peripheral immune factors. Additionally, we compare the CVMB of PLWH-ART from DRC to publicly available CVMB data (5 studies, 1861 samples) in a meta-analysis to elucidate the impact of HIV on the CVMB. Combined, these analyses revealed differences in community structure and predicted function of the microbiota between PLWH-ART and pregnant people without HIV (PWoH). Taxonomically, the CVMB of DRC PLWH-ART were enriched for Lactobacillus iners-dominated CVMBs (53%) or a diverse, polymicrobial CVMB, i.e., bacterial vaginosis (BV) (43%). Functional predictions made from these taxa suggested that protein-coupled receptors, amino sugar and nucleotide sugar metabolism, fatty acid metabolism, and polycyclic aromatic hydrocarbon degradation pathways were differentially abundant between communities. Correlation with host plasma immune factors revealed putative links between some CVMB metrics (e.g., alpha diversity and species abundance) that have been linked to adverse pregnancy and birth outcomes. ImportanceHIV remains prevalent in sub-Saharan Africa, where it has been linked to adverse birth outcomes. . Suboptimal CVMBs have shown similar links. This pilot study fills critical gaps in understanding how HIV interacts with the pregnant CVMB in populations underrepresented in microbiome research, like the Democratic Republic of Congo. We identified maternal systemic immune factors associated with suboptimal CVMBs that have been linked to poor birth outcomes. In a global meta-analysis, we found significant taxonomic and functional difference in the CVMBs between pregnant people living with and without HIV, revealing potential biomarkers that for increased risks for adverse birth outcomes. These findings provide crucial insights into CVMB features that may influence pregnancy health in pregnant people living with HIV, guiding future research and tailored interventions to support safer pregnancies in the DRC and similar populations.

microbiology↗

bioRxiv2020

HIV coinfection is associated with low fitness rpoB variants in rifampicin-resistant Mycobacterium tuberculosis

We analysed 312 drug-resistant genomes of Mycobacterium tuberculosis (Mtb) collected from HIV coinfected and HIV negative TB patients from nine countries with a high tuberculosis burden. We found that rifampicin-resistant Mtb strains isolated from HIV coinfected patients carried disproportionally more resistance-conferring mutations in rpoB that are associated with a low fitness in the absence of the drug, suggesting these low fitness rpoB variants can thrive in the context of reduced host immunity.

evolutionary biology↗

bioRxiv2019

Mortality among adults living with HIV treated for tuberculosis based on positive, negative, or no bacteriologic test results for tuberculosis: the IeDEA consortium

BackgroundIn resource-constrained settings, people living with HIV (PLWH) treated for tuberculosis (TB) despite negative bacteriologic tests have a higher mortality than those treated with positive tests. Many PLWH are treated without bacteriologic testing; their mortality compared to those with bacteriologic testing is uncertain.\n\nMethodsWe conducted an observational cohort study among PLWH [≥] 15 years of age who initiated TB treatment at clinical sites affiliated with four regions of the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium from 2012-2014: Caribbean, Central and South America, and Central, East, and West Africa. The primary exposure of interest was the TB bacteriologic test status at TB treatment initiation: positive, negative, or no test result. The hazard for death in the 12 months following TB treatment initiation was estimated using the Cox proportional hazard model, adjusted for patient- and site-level factors. Missing covariates were multiply imputed.\n\nResultsAmong 2,091 PLWH included, the median age at TB treatment initiation was 36 years, 44% were female, 53% had CD4 counts [≤] 200 cells/mm3, and 52% were on antiretroviral treatment (ART). Compared to patients with positive bacteriologic tests, the adjusted hazard for death was higher among patients with no test results (HR 1.56, 95% CI 1.08-2.26) but not different than those with negative tests (HR 1.28, 95% CI 0.91-1.81). Older age was also associated with a higher hazard for death, while being on ART, having a higher CD4 count, West Africa region, and tertiary facility level were associated with lower hazards for death.\n\nConclusionPLWH treated for TB with no bacteriologic test results were more likely to die than those treated with positive tests, underscoring the importance of TB bacteriologic diagnosis in resource-constrained settings. Research is needed to understand the causes of death among PLWH treated for TB in the absence of positive bacteriologic tests.

epidemiology↗

bioRxiv2018

Whole genome sequencing for drug resistance profile prediction in Mycobacterium tuberculosis

Whole genome sequencing allows rapid detection of drug-resistant M. tuberculosis isolates. However, high-quality data linking quantitative phenotypic drug susceptibility testing (DST) and genomic data have thus far been lacking.\n\nWe determined drug resistance profiles of 176 genetically diverse clinical M. tuberculosis isolates from Democratic Republic of the Congo, Ivory Coast, Peru, Thailand and Switzerland by quantitative phenotypic DST for 11 antituberculous drugs using the BD BACTEC MGIT 960 system and 7H10 agar dilution to generate a cross-validated phenotypic DST readout. We compared phenotypic drug susceptibility results with predicted drug resistance profiles inferred by whole genome sequencing.\n\nBoth phenotypic DST methods identically classified the strains into resistant/susceptible in 73-99% of the cases, depending on the drug. Changes in minimal inhibitory concentrations were readily explained by mutations identified by whole genome sequencing. Using the whole genome sequences we were able to predict quantitative drug resistance levels where wild type and mutant MIC distributions did not overlap. The utility of genome sequences to predict quantitative levels of drug resistance was partially limited due to incompletely understood mechanisms influencing the expression of phenotypic drug resistance. The overall sensitivity and specificity of whole genome-based DST were 86.8% and 94.5%, respectively.\n\nDespite some limitations, whole genome sequencing has high predictive power to infer resistance profiles without the need for time-consuming phenotypic methods.\n\nOne sentence summaryWhole genome sequencing of clinical M. tuberculosis isolates accurately predicts drug resistance profiles and may replace culture-based drug susceptibility testing in the future.

microbiology↗

bioRxiv2018

Drug susceptibility testing and mortality in patients treated for tuberculosis in high-burden countries

BackgroundDrug resistance and HIV co-infection are challenges for the global control of tuberculosis.\n\nMethodsWe collected Mycobacterium tuberculosis isolates from adult patients in Cote dIvoire, Democratic Republic of the Congo, Kenya, Nigeria, South Africa, Peru, and Thailand, stratified by HIV status and tuberculosis drug resistance. Molecular or phenotypic drug susceptibility testing (DST) was done locally and at the Swiss tuberculosis reference laboratory. We examined mortality during treatment according to DST results and treatment adequacy in logistic regression models adjusting for sex, age, sputum microscopy and HIV status.\n\nFindings634 tuberculosis patients were included; median age was 33.2 years, 239 (37.7%) were female, 272 (42.9%) HIV-positive and 69 (10.9%) patients died. Based on the reference laboratory DST, 394 (62.2%) strains were pan-susceptible, 45 (7.1%) mono-resistant, 163 (25.7%) multidrug-resistant (MDR-TB), and 30 (4.7%) had pre-extensive or extensive drug resistance (pre-XDR/XDR-TB). Results of reference and local laboratories were discordant in 121 (19.1%) cases, corresponding to a sensitivity of 84.3% and a specificity of 90.8%. In patients with drug-resistant tuberculosis, discordant results were associated with increased mortality (risk ratio 1.81; 95% CI 1.07-3.07). In logistic regression, compared to adequately treated patients with pan-susceptible strains, the adjusted odds ratio for death was 4.23 (95% CI 2.16-8.29) for adequately treated patients with drug-resistant strains and 21.54 (95% CI 3.36-138.1) for inadequately treated patients with drug-resistant strains. HIV status was not associated with mortality.\n\nInterpretationUsing a reference laboratory standard, inaccurate DST leading to inappropriate treatment of drug-resistant tuberculosis, but not HIV infection, contributed to mortality.

epidemiology↗