Point-of-Care Viral Load Testing for Sub-Saharan Africa: Informing a Target Product Profile.
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SUBMITTER: Phillips AN
PROVIDER: S-EPMC5047406 | biostudies-other | 2016 Sep
REPOSITORIES: biostudies-other
Publications
Point-of-Care Viral Load Testing for Sub-Saharan Africa: Informing a Target Product Profile.
Phillips Andrew N AN Cambiano Valentina V Nakagawa Fumiyo F Ford Deborah D Apollo Tsitsi T Murungu Joseph J Rousseau Christine C Garnett Geoff G Ehrenkranz Peter P Bansi-Matharu Loveleen L Vojnov Lara L Katz Zachary Z Peeling Rosanna R Revill Paul P
Open forum infectious diseases 20160729 3
Point-of-care viral load tests are being developed to monitor patients on antiretroviral therapy (ART) in sub-Saharan Africa. Test design involves trade-offs between test attributes, including accuracy, complexity, robustness, and cost. We used a model of the human immunodeficiency virus epidemic and ART program in Zimbabwe and found that the attributes of a viral load testing approach that are most influential for cost effectiveness are avoidance of a high proportion of failed tests or results ...[more]
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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.
| S-EPMC7811577 | biostudies-literature
Project description:Poor access to HIV viral load (VL) testing prevents the timely monitoring of HIV treatment adherence and efficacy. Factors enabling clinical benefits of VL testing when added to local standards of care, can inform the development of more cost-effective routine VL scale-up plans. We compared antiretroviral therapy (ART) switch practices in 13 clinics across 6 countries, with full (N = 8), phasing-in (N = 3) or no onsite access (N = 2) to VL. The analysis used data from the Pan-African Studies to Evaluate Resistance (PASER), observing virological and drug resistance outcomes among adults receiving first- or second-line ART between 2008 and 2015. Study plasma viral load (sVL) determined at baseline, every 12 months thereafter and at the time of switch served for retrospectively validating switch decisions, categorized into "necessary," "unnecessary," and "missed." Virological failure was defined as two consecutive sVL ≥1,000 HIV-RNA copies/mL. One thousand nine hundred ninety-five of the 2,420 (82.4%) study participants had continuous virological suppression during the median 30 months of follow-up. Among the 266 virological failures (11.0%), the proportion of necessary switches were similar in clinics with full (37%), phasing-in (25%), or no access (39%) to local VL testing. Documented utilization of local VL results for the switch decision was associated with higher percentage of necessary switch (87.6% vs. 67.9%). Shorter time to necessary switch was associated with higher rates of long-term virological suppression, regardless of access to local viral load. Availability of HIV VL testing capacity does not systematically result in adequate switch practices or better virological outcomes. Systems supporting sufficient test demand execution, and actual utilization of results for patient management need strengthening.
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Project description:The HIV epidemic has carved contrasting trajectories around the world with sub-Saharan Africa (SSA) being most affected. We hypothesized that mean HIV-1 plasma RNA viral loads are higher in SSA than other areas, and that these elevated levels may contribute to the scale of epidemics in this region.To evaluate this hypothesis, we constructed a database of means of 71,668 viral load measurements from 44 cohorts in seven regions of the world. We used linear regression statistical models to estimate differences in viral load between regions. We also constructed and analyzed a mathematical model to describe the impact of the regional viral load differences on HIV epidemic trajectory.We found substantial regional viral load heterogeneity. The mean viral load in SSA was 0.58 log(10) copies/ml higher than in North America (95% confidence interval 0.45-0.71); this represents about a four-fold increase. The highest mean viral loads were found in Southern and East Africa, whereas in Asia, Europe, North America, and South America, mean viral loads were comparable. Mathematical modeling indicated that conservatively 14% of HIV infections in a representative population in Kenya could be attributed to the enhanced infectiousness of patients with heightened viral load.We conclude that community viral load appears to be higher in SSA than in other regions and this may be a central driver of the massive HIV epidemics in this region. The elevated viral loads in SSA may reflect, among other factors, the high burden of co-infections or the preponderance of HIV-1 subtype C infection.
| S-EPMC3725236 | biostudies-literature
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.
2014-02-20 | GSE52791 | GEO
Project description:Using mathematical modelling, we describe the temporal evolution of population HIV-1 viral load in Tanzania throughout the epidemic. Population log10 viral load was found to be stable and not sensitive to epidemic dynamics. However, even modest increases in antiretroviral therapy (ART) coverage were reflected as appreciable reductions in population log10 viral load. As ART coverage expands in sub-Saharan Africa, population log10 viral load will increasingly become a powerful proxy for monitoring ART implementation and HIV incidence trends.
| S-EPMC3966913 | biostudies-literature
Project description:Konzo, a disease characterized by sudden, irreversible spastic paraparesis, affecting up to 10% of the population in some regions of Sub-Saharan Africa during outbreaks and is strongly associated with dietary exposure to cyanogenic bitter cassava. The molecular mechanisms underlying the development of konzo, remain largely unknown. Here, through an analysis of 16 individuals with konzo and matched healthy controls from the same outbreak zones, we identified 117 differentially methylated loci involved in numerous biological processes that may identify cyanogenic- sensitive regions of the genome, providing the first study of epigenomic alterations associated with sub-lethal cyanide exposure and a clinical phenotype.
2022-12-31 | GSE180119 | GEO
Project description:The Out-of-Africa (OOA) dispersal ∼ 50,000 y ago is characterized by a series of founder events as modern humans expanded into multiple continents. Population genetics theory predicts an increase of mutational load in populations undergoing serial founder effects during range expansions. To test this hypothesis, we have sequenced full genomes and high-coverage exomes from seven geographically divergent human populations from Namibia, Congo, Algeria, Pakistan, Cambodia, Siberia, and Mexico. We find that individual genomes vary modestly in the overall number of predicted deleterious alleles. We show via spatially explicit simulations that the observed distribution of deleterious allele frequencies is consistent with the OOA dispersal, particularly under a model where deleterious mutations are recessive. We conclude that there is a strong signal of purifying selection at conserved genomic positions within Africa, but that many predicted deleterious mutations have evolved as if they were neutral during the expansion out of Africa. Under a model where selection is inversely related to dominance, we show that OOA populations are likely to have a higher mutation load due to increased allele frequencies of nearly neutral variants that are recessive or partially recessive.
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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. The G2 PhyloChip microarray platform (commercially available from Second Genome, Inc.) was used to profile bacteria in lower airway samples from 60 subjects
2014-02-20 | E-GEOD-52791 | biostudies-arrayexpress
Project description:UnlabelledWe 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.ImportanceAfter 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.
| S-EPMC4338863 | biostudies-literature
Project description:Measurement of incidence rates of childhood cancer in Africa is difficult. The study 'Cancer of Childhood in sub Saharan Africa' [Stefan C, Bray F, Ferlay J, Parkin DM and Liu B (2017) Cancer of Childhood in sub-Saharan Africaecancer11(755)] brings together results from 16 population-based registries which, as members of the African Cancer Registry Network (AFCRN), have been evaluated as achieving adequate coverage of their target population. The cancers are classified according to the third revision of the International Classification of Childhood Cancer (ICCC-3) and recorded rates in Africa are compared with those in childhood populations in the UK, France, and the USA. It is clear that, in many centres, lack of adequate diagnostic and treatment facilities, leads to under-diagnosis (and enumeration) of leukaemias and brain cancers. However, for several childhood cancers, incidence rates in Africa are higher than those in high income countries. This applies to infection-related cancers such as Kaposi sarcoma, Burkitt lymphoma, Hodgkin lymphoma and hepatocellular carcinoma, and also to two common embryonal cancers-retinoblastoma and nephroblastoma. These (and other) observations are unlikely to be artefact, and are of considerable interest when considering possible aetiological factors, including ethnic differences in risk (and hence genetic/familial antecedents). The data reported are the most extensive so far available on the incidence of cancer in sub Saharan Africa, and clearly indicate the need for more resources to be devoted to cancer registration, especially in the childhood age range, as part of an overall programme to improve the availability of diagnosis and treatment of this group of cancers, many of which have-potentially-an excellent prognosis.
| S-EPMC5533598 | biostudies-other