The impact of HCV therapy in a high HIV-HCV prevalence population: A modeling study on people who inject drugs in Ho Chi Minh City, Vietnam

Background Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV) coinfection is a major global health problem especially among people who inject drugs (PWID), with significant clinical implications. Mathematical models have been used to great effect to shape HIV care, but few have been proposed for HIV/HCV. Methods We constructed a deterministic compartmental ODE model that incorporated layers for HIV disease progression, HCV disease progression and PWID demography. Antiretroviral therapy (ART) and Methadone Maintenance Therapy (MMT) scale-ups were modeled as from 2016 and projected forward 10 years. HCV treatment roll-out was modeled beginning in 2026, after a variety of MMT scale-up scenarios, and projected forward 10 years. Results Our results indicate that scale-up of ART has a major impact on HIV though not on HCV burden. MMT scale-up has an impact on incidence of both infections. HCV treatment roll-out has a measurable impact on reductions of deaths, increasing multifold the mortality reductions afforded by just ART/MMT scale-ups. Conclusion HCV treatment roll-out can have major and long-lasting effects on averting PWID deaths on top of those averted by ART/MMT scale-up. Efficient intervention scale-up of HCV alongside HIV interventions is critical in Vietnam

Embracing different approaches to estimating HIV incidence, prevalence and mortality

Background: Joint United Nations Programme on HIV/AIDS (UNAIDS) and Murray et al. have both produced sets of estimates for worldwide HIV incidence, prevalence and mortality. Understanding differences in these estimates can strengthen the interpretation of each

A Decline in New HIV Infections in South Africa: Estimating HIV Incidence from Three National HIV Surveys in 2002, 2005 and 2008

Three national HIV household surveys were conducted in South Africa, in 2002, 2005 and 2008. A novelty of the 2008 survey was the addition of serological testing to ascertain antiretroviral treatment (ART) use.We used a validated mathematical method to estimate the rate of new HIV infections (HIV incidence) in South Africa using nationally representative HIV prevalence data collected in 2002, 2005 and 2008. The observed HIV prevalence levels in 2008 were adjusted for the effect of antiretroviral treatment on survival. The estimated "excess" HIV prevalence due to ART in 2008 was highest among women 25 years and older and among men 30 years and older. In the period 2002-2005, the HIV incidence rate among men and women aged 15-49 years was estimated to be 2.0 new infections each year per 100 susceptible individuals (/100pyar) (uncertainty range: 1.2-3.0/100pyar). The highest incidence rate was among 15-24 year-old women, at 5.5/100pyar (4.5-6.5). In the period 2005-2008, incidence among men and women aged 15-49 was estimated to be 1.3/100 (0.6-2.5/100pyar), although the change from 2002-2005 was not statistically significant. However, the incidence rate among young women aged 15-24 declined by 60% in the same period, to 2.2/100pyar, and this change was statistically significant. There is evidence from the surveys of significant increases in condom use and awareness of HIV status, especially among youth.Our analysis demonstrates how serial measures of HIV prevalence obtained in population-based surveys can be used to estimate national HIV incidence rates. We also show the need to determine the impact of ART on observed HIV prevalence levels. The estimation of HIV incidence and ART exposure is crucial to disentangle the concurrent impact of prevention and treatment programs on HIV prevalence

Role of widows in the heterosexual transmission of HIV in Manicaland, Zimbabwe, 1998–2003

BACKGROUND: AIDS is the main driver of young widowhood in southern Africa. METHODS: The demographic characteristics of widows, their reported risk behaviours and the prevalence of HIV were examined by analysing a longitudinal population-based cohort of men and women aged 15-54 years in Manicaland, eastern Zimbabwe. The results from statistical analyses were used to construct a mathematical simulation model with the aim of estimating the contribution of widow behaviour to heterosexual HIV transmission. RESULTS: 413 (11.4%) sexually experienced women and 31 (1.2%) sexually experienced men were reported to be widowed at the time of follow-up. The prevalence of HIV was exceptionally high among both widows (61%) and widowers (male widows) (54%). Widows were more likely to have high rates of partner change and engage in a pattern of transactional sex than married women. Widowers took partners who were a median of 10 years younger than themselves. Mathematical model simulations of different scenarios of sexual behaviour of widows suggested that the sexual activity of widow(er)s may underlie 8-17% of new HIV infections over a 20-year period. CONCLUSIONS: This combined statistical analysis and model simulation suggest that widowhood plays an important role in the transmission of HIV in this rural Zimbabwean population. High-risk partnerships may be formed when widowed men and women reconnect to the sexual network

Augmenting forearm crutches with wireless sensors for lower limb rehabilitation

Forearm crutches are frequently used in the rehabilitation of an injury to the lower limb. The recovery rate is improved if the patient correctly applies a certain fraction of their body weight (specified by a clinician) through the axis of the crutch, referred to as partial weight bearing (PWB). Incorrect weight bearing has been shown to result in an extended recovery period or even cause further damage to the limb. There is currently no minimally invasive tool for long-term monitoring of a patient's PWB in a home environment. This paper describes the research and development of an instrumented forearm crutch that has been developed to wirelessly and autonomously monitor a patient's weight bearing over the full period of their recovery, including its potential use in a home environment. A pair of standard forearm crutches are augmented with low-cost off-the-shelf wireless sensor nodes and electronic components to provide indicative measurements of the applied weight, crutch tilt and hand position on the grip. Data are wirelessly transmitted between crutches and to a remote computer (where they are processed and visualized in LabVIEW), and the patient receives biofeedback by means of an audible signal when they put too much or too little weight through the crutch. The initial results obtained highlight the capability of the instrumented crutch to support physiotherapists and patients in monitoring usage

Soil pH moderates the resistance and resilience of C and N cycling to transient and persistent stress

The resilience of microbial functions like carbon (C) and nitrogen (N) cycling to stress is likely heavily dependent on pH. Past research, however, has been limited to laboratory manipulations or a pH gradient resulting from differences in soil mineralogy. In this study, soils were collected from a >50-year field trial where plots have been maintained at pH 4.9, 6 and 7.1. We selected copper (Cu) and heat to represent persistent and transient stresses, respectively. Changes in C mineralization, ammonia oxidation, denitrification, and gene (16S rRNA, nirK, nirS and amoA) abundance were immediately measured after heat- (40 °C for 16 h) and Cu- (500 μg Cu soil g−1 or 1 mg Cu soil g−1) induced stresses, during subsequent recovery over 56 days, and compared to an unstressed control. Higher soil pH significantly increased C mineralization (by 217 %), ammonia oxidation (by 617 %), and the gene abundances of 16S rRNA (by 77 %), nirK (by 976 %) and nirS (by 997 %). Soil pH had a significant (P < 0.001) selection effect on the phylotypes of bacterial communities and ammonium oxidizing bacteria (AOB). Ammonia oxidation was significantly (P < 0.05) more resistant and resilient to both Cu stresses in the pH 7.1 soil. C mineralization in the soil at pH 7.1 was significantly (P < 0.05) more resilient to low Cu than the soil at pH 4.9. Correspondingly, significantly (P < 0.001) distinct bacterial communities were present in these soils, indicating that bacterial composition triggered by the adaptation and tolerance to stress is a central factor governing functional resilience. Denitrification in the pH 7.1 soil was significantly (P < 0.05) more resilient to low and high Cu, compared to the soil at pH 4.9. Similarly, the abundances of nirS and nirK genes were greater in the higher pH soil. Although soil pH directly affects Cu but not heat stress, our results indicated that neutral soils harboured greater resilience of C and N cycling to both Cu (persistent) and heat (transient) stresses

A comparison of South African national HIV incidence estimates: A critical appraisal of different methods

BACKGROUND: The interpretation of HIV prevalence trends is increasingly difficult as antiretroviral treatment programs expand. Reliable HIV incidence estimates are critical to monitoring transmission trends and guiding an effective national response to the epidemic. Methods and FINDINGS: We used a range of methods to estimate HIV incidence in South Africa: (i) an incidence testing algorithm applying the Limiting-Antigen Avidity Assay (LAg-Avidity EIA) in combination with antiretroviral drug and HIV viral load testing; (ii) a modelling technique based on the synthetic cohort principle; and (iii) two dynamic mathematical models, the EPP/Spectrum model package and the Thembisa model. Overall, the different incidence estimation methods were in broad agreement on HIV incidence estimates among persons aged 15-49 years in 2012. The assay-based method produced slightly higher estimates of incidence, 1.72% (95% CI 1.38 - 2.06), compared with the mathematical models, 1.47% (95% CI 1.23 - 1.72) in Thembisa and 1.52% (95% CI 1.43 - 1.62) in EPP/Spectrum, and slightly lower estimates of incidence compared to the synthetic cohort, 1.9% (95% CI 0.8 - 3.1) over the period from 2008 to 2012. Among youth aged 15-24 years, a declining trend in HIV incidence was estimated by all three mathematical estimation methods. CONCLUSIONS: The multi-method comparison showed similar levels and trends in HIV incidence and validated the estimates provided by the assay-based incidence testing algorithm. Our results confirm that South Africa is the country with the largest number of new HIV infections in the world, with about 1 000 new infections occurring each day among adults aged 15-49 years in 2012

Errors in ‘BED’-Derived Estimates of HIV Incidence Will Vary by Place, Time and Age

The BED Capture Enzyme Immunoassay, believed to distinguish recent HIV infections, is being used to estimate HIV incidence, although an important property of the test--how specificity changes with time since infection--has not been not measured.We construct hypothetical scenarios for the performance of BED test, consistent with current knowledge, and explore how this could influence errors in BED estimates of incidence using a mathematical model of six African countries. The model is also used to determine the conditions and the sample sizes required for the BED test to reliably detect trends in HIV incidence.If the chance of misclassification by BED increases with time since infection, the overall proportion of individuals misclassified could vary widely between countries, over time, and across age-groups, in a manner determined by the historic course of the epidemic and the age-pattern of incidence. Under some circumstances, changes in BED estimates over time can approximately track actual changes in incidence, but large sample sizes (50,000+) will be required for recorded changes to be statistically significant.The relationship between BED test specificity and time since infection has not been fully measured, but, if it decreases, errors in estimates of incidence could vary by place, time and age-group. This means that post-assay adjustment procedures using parameters from different populations or at different times may not be valid. Further research is urgently needed into the properties of the BED test, and the rate of misclassification in a wide range of populations

What cost components are relevant for economic evaluations of palliative care, and what approaches are used to measure these costs? A systematic review

BACKGROUND: It is important to understand the costs of palliative and end-of-life care in order to inform decisions regarding cost allocation. However, economic research in palliative care is very limited and little is known about the range and extent of the costs that are involved in palliative care provision. AIM: To undertake a systematic review of the health and social care literature to determine the range of financial costs related to a palliative care approach and explore approaches used to measure these costs. DESIGN: A systematic review of empirical literature with thematic synthesis. Study quality was evaluated using the Weight of Evidence Framework. DATA SOURCES: The databases CINAHL, Cochrane, PsycINFO and Medline were searched from 1995 to November 2015 for empirical studies which presented data on the financial costs associated with palliative care. RESULTS: A total of 38 papers met our inclusion criteria. Components of palliative care costs were incurred within four broad domains: hospital care, community or home-based care, hospice care and informal care. These costs could be considered from the economic viewpoint of three providers: state or government, insurers/third-party/not-for-profit organisations and patient and family and/or society. A wide variety of costing approaches were used to derive costs. CONCLUSION: The evidence base regarding the economics of palliative care is sparse, particularly relating to the full economic costs of palliative care. Our review provides a framework for considering these costs from a variety of economic viewpoints; however, further research is required to develop and refine methodologies

Estimating HIV Incidence among Adults in Kenya and Uganda: A Systematic Comparison of Multiple Methods

CITATION: Kim, A. A. et al. 2011. Estimating HIV incidence among adults in Kenya and Uganda : a systematic comparison of multiple methods. PLos ONE, 6(3): e17535, doi:10.1371/journal.pone.0017535.The original publication is available at http://journals.plos.org/plosoneBackground: Several approaches have been used for measuring HIV incidence in large areas, yet each presents specific challenges in incidence estimation. Methodology/Principal Findings: We present a comparison of incidence estimates for Kenya and Uganda using multiple methods: 1) Epidemic Projections Package (EPP) and Spectrum models fitted to HIV prevalence from antenatal clinics (ANC) and national population-based surveys (NPS) in Kenya (2003, 2007) and Uganda (2004/2005); 2) a survey-derived model to infer age-specific incidence between two sequential NPS; 3) an assay-derived measurement in NPS using the BED IgG capture enzyme immunoassay, adjusted for misclassification using a locally derived false-recent rate (FRR) for the assay; (4) community cohorts in Uganda; (5) prevalence trends in young ANC attendees. EPP/Spectrum-derived and survey-derived modeled estimates were similar: 0.67 [uncertainty range: 0.60, 0.74] and 0.6 [confidence interval: (CI) 0.4, 0.9], respectively, for Uganda (2005) and 0.72 [uncertainty range: 0.70, 0.74] and 0.7 [CI 0.3, 1.1], respectively, for Kenya (2007). Using a local FRR, assay-derived incidence estimates were 0.3 [CI 0.0, 0.9] for Uganda (2004/2005) and 0.6 [CI 0, 1.3] for Kenya (2007). Incidence trends were similar for all methods for both Uganda and Kenya. Conclusions/Significance: Triangulation of methods is recommended to determine best-supported estimates of incidence to guide programs. Assay-derived incidence estimates are sensitive to the level of the assay's FRR, and uncertainty around high FRRs can significantly impact the validity of the estimate. Systematic evaluations of new and existing incidence assays are needed to the study the level, distribution, and determinants of the FRR to guide whether incidence assays can produce reliable estimates of national HIV incidence.http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0017535Publisher's versio