Dataset Information

Host genetic and viral determinants of HIV-1 RNA set point among HIV-1 seroconverters from sub-saharan Africa.

ABSTRACT: We quantified the collective impact of source partner HIV-1 RNA levels, human leukocyte antigen (HLA) alleles, and innate responses through Toll-like receptor (TLR) alleles on the HIV-1 set point. Data came from HIV-1 seroconverters in African HIV-1 serodiscordant couple cohorts. Linear regression was used to determine associations with set point and R(2) to estimate variation explained by covariates. The strongest predictors of set point were HLA alleles (B*53:01, B*14:01, and B*27:03) and plasma HIV-1 levels of the transmitting partner, which explained 13% and 10% of variation in set point, respectively. HLA-A concordance between partners and TLR polymorphisms (TLR2 rs3804100 and TLR7 rs179012) also were associated with set point, explaining 6% and 5% of the variation, respectively. Overall, these factors and genital factors of the transmitter (i.e., male circumcision, bacterial vaginosis, and use of acyclovir) explained 46% of variation in set point. We found that both innate and adaptive immune responses, together with plasma HIV-1 levels of the transmitting partner, explain almost half of the variation in viral load set point.After HIV-1 infection, uncontrolled virus replication leads to a rapid increase in HIV-1 concentrations. Once host immune responses develop, however, HIV-1 levels reach a peak and subsequently decline until they reach a stable level that may persist for years. This stable HIV-1 set point represents an equilibrium between the virus and host responses and is predictive of later disease progression and transmission potential. Understanding how host and virus factors interact to determine HIV-1 set point may elucidate novel mechanisms or biological pathways for treating HIV-1 infection. We identified host and virus factors that predict HIV-1 set point in people who recently acquired HIV-1, finding that both innate and adaptive immune responses, along with factors that likely influence HIV-1 virulence and inoculum, explain ?46% of the variation in HIV-1 set point.

SUBMITTER: Mackelprang RD

PROVIDER: S-EPMC4338863 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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Host genetic and viral determinants of HIV-1 RNA set point among HIV-1 seroconverters from sub-saharan Africa.

Mackelprang Romel D RD Carrington Mary M Thomas Katherine K KK Hughes James P JP Baeten Jared M JM Wald Anna A Farquhar Carey C Fife Kenneth K Campbell Mary S MS Kapiga Saida S Gao Xiaojiang X Mullins James I JI Lingappa Jairam R JR

Journal of virology 20141203 4

<h4>Unlabelled</h4>We quantified the collective impact of source partner HIV-1 RNA levels, human leukocyte antigen (HLA) alleles, and innate responses through Toll-like receptor (TLR) alleles on the HIV-1 set point. Data came from HIV-1 seroconverters in African HIV-1 serodiscordant couple cohorts. Linear regression was used to determine associations with set point and R(2) to estimate variation explained by covariates. The strongest predictors of set point were HLA alleles (B*53:01, B*14:01, an ...[more]

PMID: 25473042

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Project description:Sub-Saharan Africa represents 69% of the total number of individuals living with HIV infection worldwide and 72% of AIDS deaths globally. Pulmonary infection is a common and frequently fatal complication, though little is known regarding the lower airway microbiome composition of this population. Our objectives were to characterize the lower airway microbiome of Ugandan HIV-infected patients with pneumonia, to determine relationships with demographic, clinical, immunological, and microbiological variables and to compare the composition and predicted metagenome of these communities to a comparable cohort of patients in the US (San Francisco). Bronchoalveolar lavage samples from a cohort of 60 Ugandan HIV-infected patients with acute pneumonia were collected. Amplified 16S ribosomal RNA was profiled and aforementioned relationships examined. Ugandan airway microbiome composition and predicted metagenomic function were compared to US HIV-infected pneumonia patients. Among the most common bacterial pulmonary pathogens, Pseudomonas aeruginosa was most prevalent in the Ugandan cohort. Patients with a richer and more diverse airway microbiome exhibited lower bacterial burden, enrichment of members of the Lachnospiraceae and sulfur-reducing bacteria and reduced expression of TNF-alpha and matrix metalloproteinase-9. Compared to San Franciscan patients, Ugandan airway microbiome were significantly richer, and compositionally distinct with predicted metagenomes that encoded a multitude of distinct pathogenic pathways e.g secretion systems. Ugandan pneumonia-associated airway microbiome is compositionally and functionally distinct from those detected in comparable patients in developed countries, a feature which may contribute to adverse outcomes in this population. Please note that the data from the comparable cohort of patients in the USUS data was published as supplemental material of PMID: 22760045 but not submitted to GEO The 'patient_info.txt' contains 12 clinical, 7 immunological and 3 microbiological variables for each patient.

Project description:OBJECTIVES:To identify the determinants of antenatal care (ANC) utilisation in sub-Saharan Africa. DESIGN:Systematic review. DATA SOURCES:Databases searched were PubMed, OVID, EMBASE, CINAHL and Web of Science. ELIGIBILITY CRITERIA:Primary studies reporting on determinants of ANC utilisation following multivariate analysis, conducted in sub-Saharan Africa and published in English language between 2008 and 2018. DATA EXTRACTION AND SYNTHESIS:A data extraction form was used to extract the following information: name of first author, year of publication, study location, study design, study subjects, sample size and determinants. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist for reporting a systematic review or meta-analysis protocol was used to guide the screening and eligibility of the studies. The Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies was used to assess the quality of the studies while the Andersen framework was used to report findings. RESULTS:74 studies that met the inclusion criteria were fully assessed. Most studies identified socioeconomic status, urban residence, older/increasing age, low parity, being educated and having an educated partner, being employed, being married and Christian religion as predictors of ANC attendance and timeliness. Awareness of danger signs, timing and adequate number of antenatal visits, exposure to mass media and good attitude towards ANC utilisation made attendance and initiation of ANC in first trimester more likely. Having an unplanned pregnancy, previous pregnancy complications, poor autonomy, lack of husband's support, increased distance to health facility, not having health insurance and high cost of services negatively impacted the overall uptake, timing and frequency of antenatal visits. CONCLUSION:A variety of predisposing, enabling and need factors affect ANC utilisation in sub-Saharan Africa. Intersectoral collaboration to promote female education and empowerment, improve geographical access and strengthened implementation of ANC policies with active community participation are recommended.

Dataset Information

Host genetic and viral determinants of HIV-1 RNA set point among HIV-1 seroconverters from sub-saharan Africa.

Publications

Host genetic and viral determinants of HIV-1 RNA set point among HIV-1 seroconverters from sub-saharan Africa.

Similar Datasets

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