Effect of stigma reduction intervention strategies on HIV test uptake in low- and middle-income countries: a realist review protocol

Background Several stigma reduction intervention strategies have been developed and tested for effectiveness in terms of increasing human immunodeficiency virus (HIV) test uptake. These strategies have been more effective in some contexts and less effective in others. Individual factors, such as lack of knowledge and fear of disclosure, and social-contextual factors, such as poverty and illiteracy, might influence the effect of stigma reduction intervention strategies on HIV test uptake in low- and middle-income countries. So far, it is not clearly known how the stigma reduction intervention strategies interact with these contextual factors to increase HIV test uptake. Therefore, we will conduct a review that will synthesize existing studies on stigma reduction intervention strategies to increase HIV test uptake to better understand the mechanisms underlying this process in low- and middle-income countries. Methods A realist review will be conducted to unpack context-mechanism-outcome configurations of the effect of stigma reduction intervention strategies on HIV test uptake. Based on a scoping review, we developed a preliminary theoretical framework outlining a potential mechanism of how the intervention strategies influence HIV test uptake. Our realist synthesis will be used to refine the preliminary theoretical framework to better reflect mechanisms that are supported by existing evidence. Journal articles and grey literature will be searched following a purposeful sampling strategy. Data will be extracted and tested against the preliminary theoretical framework. Data synthesis and analysis will be performed in five steps: organizing extracted data into evidence tables, theming, formulating chains of inference from the identified themes, linking the chains of inference and developing generative mechanisms, and refining the framework. Discussion This will be the first realist review that offers both a quantitative and a qualitative exploration of the available evidence to develop and propose a theoretical framework that explains why and how HIV stigma reduction intervention strategies influence HIV test uptake in low- and middle-income countries. Our theoretical framework is meant to provide guidance to program managers on identifying the most effective stigma reduction intervention strategies to increase HIV test uptake. We also include advice on how to effectively implement these strategies to reduce the rate of HIV transmission.status: publishe

Modelling the Effect of Temperature on Respiration Rate of Fresh Cut Papaya (Carica papaya L.) Fruits.

A respiration rate (RR) model based on Peleg’s equation was developed for predicting RRs of fresh cut papaya. Respiration data for fresh cut papaya at 3/4 maturity were generated at temperatures 5, 10, 15, 20, 25 and 30°C using a closed system. RRs was found to be significantly influenced by storage temperature and increased from 0.021 to 0.289 mL[O2]/kg·h and 0.063 to 0.393 mL[CO2]/kg·h as a function of O2 and CO2 gas concentrations, respectively. Peleg’s constant K 1 and K 2 were obtained from linear regression analysis using GraphPad Prism 5.0 software and regression coefficients have good fit with values close to unity. The model was verified to assess the capability of its predictability of the RRs over the temperatures. There was good agreement with the experimentally estimated RRs. Information derived from the model can contribute in the design of successful modified atmospheric systems for storage of fresh cut papaya

Developing a matrix to identify and prioritise research recommendations in HIV Prevention

BACKGROUND: HIV prevention continues to be problematic in the UK, as it does globally. The UK Department of Health has a strategic direction with greater focus on prevention as part of its World Class Commissioning Programme. There is a need for targeted evidence-based prevention initiatives. This is an exploratory study to develop an evidence mapping tool in the form of a matrix: this will be used to identify important gaps in contemporary HIV prevention evidence relevant to the UK. It has the potential to aid prioritisation in future research.METHODS: Categories for prevention and risk groups were developed for HIV prevention in consultation with external experts. These were used as axes on a matrix tool to map evidence. Systematic searches for publications on HIV prevention were undertaken using electronic databases for primary and secondary research undertaken mainly in UK, USA, Canada, Australia and New Zealand, 2006-9. Each publication was screened for inclusion then coded. The risk groups and prevention areas in each paper were counted: several publications addressed multiple risk groups. The counts were exported to the matrix and clearly illustrate the concentrations and gaps of literature in HIV prevention.RESULTS: 716 systematic reviews, randomised control trials and other primary research met the inclusion criteria for HIV prevention. The matrix identified several under researched areas in HIV prevention.CONCLUSIONS: This is the first categorisation system for HIV prevention and the matrix is a novel tool for evidence mapping. Some important yet under-researched areas have been identified in HIV prevention evidence: identifying the undiagnosed population; international adaptation; education; intervention combinations; transgender; sex-workers; heterosexuals and older age groups.<br/

Predictors of early death in a cohort of Ethiopian patients treated with HAART

BACKGROUND: HAART has improved the survival of HIV infected patients. However, compared to patients in high-income countries, patients in resource-poor countries have higher mortality rates. Our objective was to identify independent risk factors for death in Ethiopian patients treated with HAART. METHODS: In a district hospital in Ethiopia, we treated adult HIV infected patients with HAART based on clinical and total lymphocyte count (TLC) criteria. We measured body weight and complete blood cell count at baseline, 4 weeks later, then repeated weight every month and complete blood cell count every 12 weeks. Time to death was the main outcome variable. We used the Kaplan Meier and Cox regression survival analyses to identify prognostic markers. Also, we calculated mortality rates for the different phases of the follow-up. RESULTS: Out of 162 recruited, 152 treatment-naïve patients contributed 144.1 person-years of observation (PYO). 86 (57%) of them were men and their median age was 32 years. 24 patients died, making the overall mortality rate 16.7 per 100 PYO. The highest death rate occurred in the first month of treatment. Compared to the first month, mortality declined by 9-fold after the 18(th )week of follow-up. Being in WHO clinical stage IV and having TLC<= 750/mcL were independent predictors of death. Haemoglobin (HGB) <= 10 g/dl and TLC<= 1200/mcL at baseline were not associated with increased mortality. Body mass index (BMI) <= 18.5 kg/m2 at baseline was associated with death in univariate analysis. Weight loss was seen in about a third of patients who survived up to the fourth week, and it was associated with increased death. Decline in TLC, HGB and BMI was associated with death in univariate analysis only. CONCLUSION: The high mortality rate seen in this cohort was associated with advanced disease stage and very low TLC at presentation. Patients should be identified and treated before they progress to advanced stages. The underlying causes for early death in patients presenting at late stages should be investigated

Formative Assessment of ARM-U: A Modular Intervention for Decreasing Risk Behaviors Among HIV-Positive and HIV-Negative Methamphetamine-Using MSM

BACKGROUND: Methamphetamine is a major contributor to HIV transmission among men who have sex with men (MSM). Recent studies show that up to one-third of methamphetamine-using MSM (MUMSM) inject the drug. We developed a behavioral intervention for MUMSM to decrease unprotected anal intercourse and increase awareness of parenteral HIV transmission risk. This 6-session (3 in-person, 3 by telephone) modular intervention was designed to be tailored to participants' HIV (+/-) and injection drug user ([IDU] yes/no) status. We present results of formative research used to evaluate the content and to assess feasibility and acceptability of this individual-level HIV risk-reduction intervention. SETTING: HIV research clinic in a high MSM and methamphetamine prevalence neighborhood. PROJECT: Avoiding Risks from Methamphetamine-Use (ARM-U) is a brief toolbox intervention that allows counselors to select modules that suit a client's individual risk profile and intervention needs employing motivational interviewing and cognitive behavioral theory. We evaluated the format and content of the intervention through focus groups and pre-testing of the entire intervention using volunteers from the target population stratified into four groups (HIV+/IDU, HIV-/IDU, HIV+/non-IDU, HIV-/non-IDU). Four individuals in each stratum were recruited to undergo the intervention and complete a satisfaction survey at the end of each in-person session. RESULTS: In total, 25 MUMSM attended one of five focus groups. Participants thought all proposed intervention topics were important and could aid in reducing sexual risk behaviors among MUMSM. However, the neurocognitive effects of methamphetamine were reported to be a barrier to practicing safer sex, condom use negotiation or HIV status disclosure. Fifteen (94%) of 16 participants completed all 6 sessions and the satisfaction survey. On average, participants felt the intervention was useful for MUMSM, made them contemplate and move toward behavior change, and would recommend the program to their peers. LESSONS LEARNED: Based on our formative research, we revised the ARM-U intervention to emphasize pre-planning to avoid combining methamphetamine use and sex or develop strategies to avoid sex risk following methamphetamine use. We also increased emphasis on referrals for care and other requested services. Future efficacy trials are needed to evaluate the intervention's ability to reduce HIV-associated risk behaviors

Plasma Proteomic Profiling in HIV-1 Infected Methamphetamine Abusers

We wanted to determine whether methamphetamine use affects a subset of plasma proteins in HIV-infected persons. Plasma samples from two visits were identified for subjects from four groups: HIV+, ongoing, persistent METH use; HIV+, short-term METH abstinent; HIV+, long term METH abstinence; HIV negative, no history of METH use. Among 390 proteins identified, 28 showed significant changes in expression in the HIV+/persistent METH+ group over the two visits, which were not attributable to HIV itself. These proteins were involved in complement, coagulation pathways and oxidative stress. Continuous METH use is an unstable condition, altering levels of a number of plasma proteins

Methamphetamine Increases LPS-Mediated Expression of IL-8, TNF-α and IL-1β in Human Macrophages through Common Signaling Pathways

The use of methamphetamine (MA) has increased in recent years, and is a major health concern throughout the world. The use of MA has been associated with an increased risk of acquiring HIV-1, along with an increased probability of the acquisition of various sexually transmitted infections. In order to determine the potential effects of MA exposure in the context of an infectious agent, U937 macrophages were exposed to various combinations of MA and bacterial lipopolysaccharide (LPS). Treatment with MA alone caused significant increases in the levels of TNF-α, while treatment with both MA and LPS resulted in significant increases in TNF-α, IL-1β and the chemokine IL-8. The increases in cytokine or chemokine levels seen when cells were treated with both LPS and MA were generally greater than those increases observed when cells were treated with only LPS. Treatment with chemical inhibitors demonstrated that the signal transduction pathways including NF-kB, MAPK, and PI3-Akt were involved in mediating the increased inflammatory response. As discussed in the paper, these pathways appear to be utilized by both MA and LPS, in the induction of these inflammatory mediators. Since these pathways are involved in the induction of inflammation in response to other pathogens, this suggests that MA-exacerbated inflammation may be a common feature of infectious disease in MA abusers

Allergen particle binding by human primary bronchial epithelial cells is modulated by surfactant protein D

<p>Abstract</p> <p>Background</p> <p>Allergen-containing subpollen particles (SPP) are released from whole plant pollen upon contact with water or even high humidity. Because of their size SPP can preferentially reach the lower airways where they come into contact with surfactant protein (SP)-D. Our previous work demonstrated that SP-D increases the uptake of SPP by alveolar macrophages. In the present study, we investigated the uptake of SPP in human primary epithelial cells and the potential modulation by SP-D. The patho-physiological consequence was evaluated by measurement of pro-inflammatory mediators.</p> <p>Methods</p> <p>SPP were isolated from timothy grass and subsequently fluorescently labelled. Human primary bronchial epithelial cells were incubated with SPP or polystyrene particles (PP) in the presence and absence of surfactant protein D. In addition, different sizes and surface charges of the PP were studied. Particle uptake was evaluated by flow cytometry and confocal microscopy. Soluble mediators were measured by enzyme linked immunosorbent assay or bead array.</p> <p>Results</p> <p>SPP were taken up by primary epithelial cells in a dose dependent manner. This uptake was coincided with secretion of Interleukin (IL)-8. SP-D increased the fraction of bronchial epithelial cells that bound SPP but not the fraction of cells that internalized SPP. SPP-induced secretion of IL-8 was further increased by SP-D. PP were bound and internalized by epithelial cells but this was not modulated by SP-D.</p> <p>Conclusions</p> <p>Epithelial cells bind and internalize SPP and PP which leads to increased IL-8 secretion. SP-D promotes attachment of SPP to epithelial cells and may thus be involved in the inflammatory response to inhaled allergen.</p

Morphine Induces Expression of Platelet-Derived Growth Factor in Human Brain Microvascular Endothelial Cells: Implication for Vascular Permeability

Despite the advent of antiretroviral therapy, complications of HIV-1 infection with concurrent drug abuse are an emerging problem. Morphine, often abused by HIV-infected patients, is known to accelerate neuroinflammation associated with HIV-1 infection. Detailed molecular mechanisms of morphine action however, remain poorly understood. Platelet-derived growth factor (PDGF) has been implicated in a number of pathological conditions, primarily due to its potent mitogenic and permeability effects. Whether morphine exposure results in enhanced vascular permeability in brain endothelial cells, likely via induction of PDGF, remains to be established. In the present study, we demonstrated morphine-mediated induction of PDGF-BB in human brain microvascular endothelial cells, an effect that was abrogated by the opioid receptor antagonist-naltrexone. Pharmacological blockade (cell signaling) and loss-of-function (Egr-1) approaches demonstrated the role of mitogen-activated protein kinases (MAPKs), PI3K/Akt and the downstream transcription factor Egr-1 respectively, in morphine-mediated induction of PDGF-BB. Functional significance of increased PDGF-BB manifested as increased breach of the endothelial barrier as evidenced by decreased expression of the tight junction protein ZO-1 in an in vitro model system. Understanding the regulation of PDGF expression may provide insights into the development of potential therapeutic targets for intervention of morphine-mediated neuroinflammation