Joachim Voss

Expression of toll-like receptors by human muscle cells in vitro and in vivo: TLR3 is highly expressed in inflammatory and HIV myopathies, mediates IL-8 release and up-regulation of NKG2D-ligands

The particular microenvironment of the skeletal muscle can be the site of complex immune reactions. Toll‐like receptors (TLRs) mediate inflammatory stimuli from pathogens and endogenous danger signals and link the innate and adaptive immune system. We investigated innate immune responses in human muscle. Analyzing TLR1–9 mRNA in cultured myoblasts and rhabdomyosarcoma cells, we found constitutive expression of TLR3. The TLR3 ligand Poly (I:C), a synthetic analog of dsRNA, and IFN‐γ increased TLR3 levels. TLR3 was mainly localized intracellularly and regulated at the protein level. Poly (I:C) challenge 1) activated nuclear factor‐κB (NF‐κB), 2) increased IL‐8 release, and 3) up‐regulated NKG2D ligands and NK‐cell‐mediated lysis of muscle cells. We examined muscle biopsy specimens of 6 HIV patients with inclusion body myositis/polymyositis (IBM/PM), 7 cases of sporadic IBM and 9 nonmyopathic controls for TLR3 expression. TLR3 mRNA levels were elevated in biopsy specimens from patients with IBM and HIV‐myopathies. Muscle fibers in inflammatory myopathies expressed TLR3 in close proximity of infiltrating mononuclear cells. Taken together, our study suggests an important role of TLR3 in the immunobiology of muscle, and has substantial implications for the understanding of the pathogenesis of inflammatory myopathies or therapeutic interventions like vaccinations or gene transfer.

Does "Asymptomatic" Mean Without Symptoms for Those Living with HIV Infection?

Abstract Throughout the history of the HIV epidemic, HIV-positive patients with relatively high CD4 counts and no clinical features of opportunistic infections have been classified as “asymptomatic” by definition and treatment guidelines. This classification, however, does not take into consideration the array of symptoms that an HIV-positive person can experience long before progressing to AIDS. This short report describes two international multi-site studies conducted in 2003–2005 and 2005–2007. The results from the studies show that HIV-positive people may experience symptoms throughout the trajectory of their disease, regardless of CD4 count or classification. Providers should discuss symptoms and symptom management with their clients at all stages of the disease.

Focus on Increasing Treatment Self-Efficacy to Improve Human Immunodeficiency Virus Treatment Adherence

PURPOSE Human immunodeficiency virus (HIV) treatment self-efficacy is the confidence held by an individual in her or his ability to follow treatment recommendations, including specific HIV care such as initiating and adhering to antiretroviral therapy (ART). The purpose of this study was to explore the potential mediating role of treatment adherence self-efficacy in the relationships between Social Cognitive Theory constructs and self- reported ART adherence. DESIGN Cross-sectional and descriptive. The study was conducted between 2009 and 2011 and included 1,414 participants who lived in the United States or Puerto Rico and were taking antiretroviral medications. METHODS Social cognitive constructs were tested specifically: behaviors (three adherence measures each consisting of one item about adherence at 3-day and 30-day along with the adherence rating scale), cognitive or personal factors (the Center for Epidemiology Studies Depression Scale to assess for depressive symptoms, the 12-Item Short Form Health Survey (SF-12) to assess physical functioning, one item about physical condition, one item about comorbidity), environmental influences (the Social Capital Scale, one item about social support), and treatment self-efficacy (HIV Adherence Self-Efficacy Scale). Analysis included descriptive statistics and regression. RESULTS The average participant was 47 years old, male, and a racial or ethnic minority, had an education of high school or less, had barely adequate or totally inadequate income, did not work, had health insurance, and was living with HIV/acquired immunodeficiency syndrome for 15 years. The model provided support for adherence self-efficacy as a robust predictor of ART adherence behavior, serving a partial mediating role between environmental influences and cognitive or personal factors. CONCLUSIONS Although other factors such as depressive symptoms and lack of social capital impact adherence to ART, nurses can focus on increasing treatment self-efficacy through diverse interactional strategies using principles of adult learning and strategies to improve health literacy. CLINICAL RELEVANCE Adherence to ART reduces the viral load thereby decreasing morbidity and mortality and risk of transmission to uninfected persons. Nurses need to use a variety of strategies to increase treatment self-efficacy.

Depressive Symptoms, Self-Esteem, HIV Symptom Management Self-Efficacy and Self-Compassion in People Living with HIV

The aims of this study were to examine differences in self-schemas between persons living with HIV/AIDS with and without depressive symptoms, and the degree to which these self-schemas predict depressive symptoms in this population. Self-schemas are beliefs about oneself and include self-esteem, HIV symptom management self-efficacy, and self-compassion. Becks cognitive theory of depression guided the analysis of data from a sample of 1766 PLHIV from the USA and Puerto Rico. Sixty-five percent of the sample reported depressive symptoms. These symptoms were significantly (p ≤ 0.05), negatively correlated with age (r = −0.154), education (r = −0.106), work status (r = −0.132), income adequacy (r = −0.204, self-esteem (r = −0.617), HIV symptom self-efficacy (r = − 0.408), and self-kindness (r = − 0.284); they were significantly, positively correlated with gender (female/transgender) (r = 0.061), white or Hispanic race/ethnicity (r = 0.047) and self-judgment (r = 0.600). Fifty-one percent of the variance (F = 177.530 (df = 1524); p < 0.001) in depressive symptoms was predicted by the combination of age, education, work status, income adequacy, self-esteem, HIV symptom self-efficacy, and self-judgment. The strongest predictor of depressive symptoms was self-judgment. Results lend support to Becks theory that those with negative self-schemas are more vulnerable to depression and suggest that clinicians should evaluate PLHIV for negative self-schemas. Tailored interventions for the treatment of depressive symptoms in PLHIV should be tested and future studies should evaluate whether alterations in negative self-schemas are the mechanism of action of these interventions and establish causality in the treatment of depressive symptoms in PLHIV.

A cross-sectional description of social capital in an international sample of persons living with HIV/AIDS (PLWH)

BackgroundSocial capital refers to the resources linked to having a strong social network. This concept plays into health outcomes among People Living with HIV/AIDS because, globally, this is a highly marginalized population. Case studies show that modifying social capital can lead to improvements in HIV transmission and management; however, there remains a lack of description or definition of social capital in international settings. The purpose of our paper was to describe the degree of social capital in an international sample of adults living with HIV/AIDS.MethodsWe recruited PLWH at 16 sites from five countries including Canada, China, Namibia, Thailand, and the United States. Participants (n = 1,963) completed a cross-sectional survey and data were collected between August, 2009 and December, 2010. Data analyses included descriptive statistics, factor analysis, and correlational analysis.ResultsParticipants mean age was 45.2 years, most (69%) identified as male, African American/Black (39.9%), and unemployed (69.5%). Total mean social capital was 2.68 points, a higher than average total social capital score. Moderate correlations were observed between self-reported physical (r = 0.25) and psychological condition (r = 0.36), social support (r = 0.31), and total social capital. No relationships between mental health factors, including substance use, and social capital were detected.ConclusionsThis is the first report to describe levels of total social capital in an international sample of PLWH and to describe its relationship to self-reported health in this population.

Development of Evidence-Based Exercise Recommendations for Older HIV-Infected Patients

&NA; Advances in antiretroviral therapy (ART) have decreased HIV‐related morbidity and mortality and contributed to rapidly increasing numbers of older people living with HIV. Successful management of ART‐related side effects (metabolic syndrome) and age‐related comorbidities (frailty) are major challenges for patients and providers. Exercise has proven beneficial for younger HIV‐infected patients, but we know little about which exercise regimens to recommend to the elderly. Our goal was to develop age‐appropriate, evidence‐based exercise recommendations for older HIV‐infected adults (age > 50). We reviewed randomized controlled trials on the effects of physical exercise for: (a) HIV‐infected young adults, (b) frail older adults, and (c) elderly individuals with metabolic syndrome. We recommend a combination of endurance and resistance exercises 3 times per week for at least 6 weeks to improve cardiovascular, metabolic, and muscle function. Further research is warranted to study the benefits and risks of physical exercise in older HIV‐infected patients.

Unhealthy behaviours for self-management of HIV-related peripheral neuropathy

Abstract The prevalence of peripheral neuropathy is frequent in HIV disease and is often associated with antiretroviral therapy. Unhealthy behaviours, particularly substance-use behaviours, are utilized by many HIV-positive individuals to manage neuropathic symptoms. As part of a larger study on self-care for symptoms in HIV disease, this study analyzed the prevalence and characteristics of unhealthy behaviours to self-manage peripheral neuropathy in HIV disease. Sociodemographic and disease-related correlates and unhealthy behaviours were examined in a convenience sample of 1,217 respondents who were recruited from data collection sites in several US cities, Puerto Rico, Colombia, and Taiwan. Results of the study indicated that respondents with peripheral neuropathy (n=450) identified a variety of unhealthy self-care behaviours including injection drug use, oral drug use, smoking cigarettes and alcohol ingestion. Specific unhealthy behaviours that participants reported to alleviate peripheral neuropathy included use of marijuana (n=67), smoking cigarettes (n=139), drinking alcohol (n=81) and street drugs (n=30). A subset of those individuals (n=160), who identified high levels of neuropathy (greater than five on a scale of 1–10), indicated significantly higher use of amphetamines and injection drug use in addition to alcohol use and cigarette smoking. For participants from Norway, substance use (using alcohol: 56%) was one of the most frequent self-management strategies. Implications for clinical practice include assessment and education of persons with HIV for self-care management of the complex symptom of peripheral neuropathy.

HIV Infection and Antiretroviral Therapy Have Divergent Effects on Mitochondria in Adipose Tissue

BACKGROUND Although human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) affect mitochondrial DNA (mtDNA) content and function, comprehensive evaluations of their effects on mitochondria in muscle, adipose tissue, and blood cells are limited. METHODS Mitochondrial DNA quantification, mitochondrial genome sequencing, and gene expression analysis were performed on muscle, adipose tissue, and peripheral blood mononuclear cell (PBMC) samples from untreated HIV-positive patients, HIV-positive patients receiving nucleoside reverse transcriptase inhibitor (NRTI)-based ART, and HIV-negative controls. RESULTS The adipose tissue mtDNA/nuclear DNA (nDNA) ratio was increased in untreated HIV-infected patients (ratio, 353) and decreased in those receiving ART (ratio, 162) compared with controls (ratio, 255; P < .05 for both comparisons); the difference between the 2 HIV-infected groups was also significant (P = .002). In HIV-infected participants, mtDNA/nDNA in adipose tissue correlated with the level of activation (CD38+ /HLA-DR+) for CD4+ and CD8+ lymphocytes. No significant differences in mtDNA content were noted in muscle or PMBCs among groups. Exploratory DNA microarray analysis identified differential gene expression between patient groups, including a subset of adipose tissue genes. CONCLUSIONS HIV infection and ART have opposing effects on mtDNA content in adipose tissue; immune activation may mediate the effects of HIV, whereas NRTIs likely mediate the effects of ART.

Nursing and midwifery regulation and HIV scale-up: establishing a baseline in east, central and southern Africa

Shifting HIV treatment tasks from physicians to nurses and midwives is essential to scaling‐up HIV services in sub‐Saharan Africa. Updating nursing and midwifery regulations to include task shifting and pre‐service education reform can help facilitate reaching new HIV targets. Donor‐supported initiatives to update nursing and midwifery regulations are increasing. However, there are gaps in our knowledge of current practice and education regulations and a lack of information to target and implement regulation strengthening efforts. We conducted a survey of national nursing and midwifery councils to describe current nursing and midwifery regulations in 13 African countries.

Nursing and midwifery regulatory reform in east, central, and southern Africa: a survey of key stakeholders

BackgroundIn sub-Saharan Africa, nurses and midwives provide expanded HIV services previously seen as the sole purview of physicians. Delegation of these functions often occurs informally by shifting or sharing of tasks and responsibilities. Normalizing these arrangements through regulatory and educational reform is crucial for the attainment of global health goals and the protection of practitioners and those whom they serve. Enacting appropriate changes in both regulation and education requires engagement of national regulatory bodies, but also key stakeholders such as government chief nursing officers (CNO), professional associations, and educators. The purpose of this research is to describe the perspectives and engagement of these stakeholders in advancing critical regulatory and educational reform in east, central, and southern Africa (ECSA).MethodsWe surveyed individuals from these three stakeholder groups with regard to task shifting and the challenges related to practice and education regulation reform. The survey used a convenience sample of nursing and midwifery leaders from countries in ECSA who convened on 28 February 2011, for a meeting of the African Health Profession Regulatory Collaborative.ResultsA total of 32 stakeholders from 13 ECSA countries participated in the survey. The majority (72%) reported task shifting is practiced in their countries; however only 57% reported their national regulations had been revised to incorporate additional professional roles and responsibilities. Stakeholders also reported different roles and levels of involvement with regard to nursing and midwifery regulation. The most frequently cited challenge impacting nursing and midwifery regulatory reform was the absence of capacity and resources needed to implement change.DiscussionWhile guidelines on task shifting and recommendations on transforming health professional education exist, this study provides new evidence that countries in the ECSA region face obstacles to adapting their practice and education regulations accordingly. Stakeholders such as CNOs, nursing associations, and academicians have varied and complementary roles with regard to reforming professional practice and education regulation.ConclusionThis study provides information for effectively engaging leaders in regulatory reform by clarifying their roles, responsibilities, and activities regarding regulation overall as well as their specific perspectives on task shifting and pre-service reform.