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: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. The G2 PhyloChip microarray platform (commercially available from Second Genome, Inc.) was used to profile bacteria in lower airway samples from 60 subjects

Project description:IntroductionIn many low- and middle-income countries, HIV viral load (VL) testing occurs at centralized laboratories and time-to-result-delivery is lengthy, preventing timely monitoring of HIV treatment adherence. Near point-of-care (POC) devices, which are placed within health facility laboratories rather than clinics themselves (i.e. "true" POC), can offer VL in conjunction with centralized laboratories to expedite clinical decision making and improve outcomes, especially for patients at high risk of treatment failure. We assessed impacts of near-POC VL testing on result receipt and clinical action in public sector programmes in Cameroon, Democratic Republic of Congo, Kenya, Malawi, Senegal, Tanzania and Zimbabwe.MethodsRoutine health data were collected retrospectively after introducing near-POC VL testing at 57 public sector health facilities (2017 to 2019, country-dependent). Where possible, key indicators were compared to data from patients receiving centralized laboratory testing using hazard ratios and the Somers' D test.ResultsData were collected from 6795 tests conducted on near-POC and 17614 tests on centralized laboratory-based platforms. Thirty-one percent (2062/6694) of near-POC tests were conducted for high-risk populations: pregnant and breastfeeding women, children and those with suspected failure. Compared to conventional testing, near-POC improved the median time from sample collection to return of results to patient [six vs. sixty-eight days, effect size: -32.2%; 95% CI: -41.0% to -23.4%] and to clinical action for individuals with an elevated HIV VL [three vs. fourty-nine days, effect size: -35.4%; 95% CI: -46.0% to -24.8%]. Near-POC VL results were two times more likely to be returned to the patient within 90 days compared to centralized tests [50% (1781/3594) vs. 27% (4172/15271); aHR: 2.22, 95% CI: 2.05 to 2.39]. Thirty-seven percent (340/925) of patients with an elevated near-POC HIV VL result had documented clinical follow-up actions within 30 days compared to 7% (167/2276) for centralized testing.ConclusionsNear-POC VL testing enabled rapid test result delivery for high-risk populations and led to significant improvements in the timeliness of patient result receipt compared to centralized testing. While there was some improvement in time-to-clinical action with near-POC VL testing, major gaps remained. Strengthening of systems supporting the utilization of results for patient management are needed to truly capitalize on the benefits of decentralized testing.

Project description:BackgroundWe examined the epidemiology and transmission potential of HIV population viral load (VL) in 12 sub-Saharan African countries.MethodsWe analyzed data from Population-based HIV Impact Assessments (PHIAs), large national household-based surveys conducted between 2015 and 2019 in Cameroon, Cote d'Ivoire, Eswatini, Kenya, Lesotho, Malawi, Namibia, Rwanda, Tanzania, Uganda, Zambia, and Zimbabwe. Blood-based biomarkers included HIV serology, recency of HIV infection, and VL. We estimated the number of people living with HIV (PLHIV) with suppressed viral load (<1,000 HIV-1 RNA copies/mL) and with unsuppressed viral load (viremic), the prevalence of unsuppressed HIV (population viremia), sex-specific HIV transmission ratios (number female incident HIV-1 infections/number unsuppressed male PLHIV per 100 persons-years [PY] and vice versa) and examined correlations between a variety of VL metrics and incident HIV. Country sample sizes ranged from 10,016 (Eswatini) to 30,637 (Rwanda); estimates were weighted and restricted to participants 15 years and older.ResultsThe proportion of female PLHIV with viral suppression was higher than that among males in all countries, however, the number of unsuppressed females outnumbered that of unsuppressed males in all countries due to higher overall female HIV prevalence, with ratios ranging from 1.08 to 2.10 (median: 1.43). The spatial distribution of HIV seroprevalence, viremia prevalence, and number of unsuppressed adults often differed substantially within the same countries. The 1% and 5% of PLHIV with the highest VL on average accounted for 34% and 66%, respectively, of countries' total VL. HIV transmission ratios varied widely across countries and were higher for male-to-female (range: 2.3-28.3/100 PY) than for female-to-male transmission (range: 1.5-10.6/100 PY). In all countries mean log10 VL among unsuppressed males was higher than that among females. Correlations between VL measures and incident HIV varied, were weaker for VL metrics among females compared to males and were strongest for the number of unsuppressed PLHIV per 100 HIV-negative adults (R2 = 0.92).ConclusionsDespite higher proportions of viral suppression, female unsuppressed PLHIV outnumbered males in all countries examined. Unsuppressed male PLHIV have consistently higher VL and a higher risk of transmitting HIV than females. Just 5% of PLHIV account for almost two-thirds of countries' total VL. Population-level VL metrics help monitor the epidemic and highlight key programmatic gaps in these African countries.

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Have the explosive HIV epidemics in sub-Saharan Africa been driven by higher community viral load?

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Have the explosive HIV epidemics in sub-Saharan Africa been driven by higher community viral load?

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