Interventions for Neurocognitive Dysfunction

Purpose of Review

This study aimed to evaluate current barriers to HIV cure strategies and interventions for neurocognitive dysfunction with a particular focus on recent advancements over the last 3 years.

Recent Findings

Optimal anti-retroviral therapy (ART) poses challenges to minimise neurotoxicity, whilst ensuring blood-brain barrier penetration and minimising the risk of cerebrovascular disease. CSF biomarkers, BCL11B and neurofilament light chain may be implicated with a neuroinflammatory cascade leading to cognitive impairment. Diagnostic imaging with diffusion tensor imaging and resting-state fMRI show promise in future diagnosis and monitoring of HAND.

Summary

The introduction of ART has resulted in a dramatic decline in HIV-associated dementia. Despite this reduction, milder forms of HIV-associated neurocognitive disorder (HAND) are still prevalent and are clinically significant. The central nervous system (CNS) has been recognised as a probable reservoir and sanctuary for HIV, representing a significant barrier to management interventions.

     

<Emphasis Type="Italic">Helicobacter bilis</Emphasis>-Associated Suppurative Cholangitis in a Patient with X-Linked Agammaglobulinemia

?

Helicobacter bilis is a commensal bacterium causing chronic hepatitis and colitis in mice. In humans, enterohepatic Helicobacter spp. are associated with chronic hepatobiliary diseases.

Purpose

We aimed at understanding the microbial etiology in a patient with X-linked agammaglobulinemia presenting with suppurative cholangitis.

Methods

16S rDNA PCR directly performed on a liver biopsy retrieved DNA of H. bilis.

Results

Clinical outcome resulted in the normalization of clinical and biological parameters under antibiotic treatment by a combination of ceftriaxone, metronidazole, and doxycyclin followed by a 2-week treatment with moxifloxacin and a 2-month treatment with azithromycin.

Conclusion

In conclusion, these data suggest a specific clinical and microbiological approach in patients with humoral deficiency in order to detect H. bilis hepatobiliary diseases.

     

Successful use of extracorporeal membrane oxygenation in a human immunodeficiency virus infected patient with severe acute respiratory distress syndrome

Introduction

We report a case of an adult patient with human immunodeficiency virus (HIV), acute respiratory distress syndrome (ARDS) and ventilator associated pneumonia (VAP) caused by multidrug resistant (MDR) bacteria that was successfully managed with veno-venous extracorporeal membrane oxygenation (ECMO).

Case report

A 25 year old male with no significant past medical history had been admitted to a local hospital due to dyspnea and fever. His pulmonary function subsequently failed necessitating mechanical ventilation (MV) and introduction of ECMO support. The patient was transported for 300 km by road on ECMO to a tertiary medical center. The diagnosis of ARDS, HIV infection and MDR bacterial and fungal VAP was made. Patient was successfully treated with antiretroviral therapy (ART), anti-infective agents and 58 days of veno-venous ECMO support, with complete resolution of the respiratory symptoms.

Conclusion

HIV infected patients with ARDS and MDR bacterial VAP whose HIV replication is controlled by ART could be successfully managed with ECMO.

     

HIV patients stable on ART retain evidence of a high CMV load but changes to Natural Killer cell phenotypes reflect both HIV and CMV

Background

Whilst ART corrects many effects of HIV disease, T cell populations retain features of accelerated immunological aging.

Methods

Here we analyse phenotypic changes to natural killer (NK) cells in HIV patients who began ART with <200 CD4 T-cells/µl and maintained virological control for 12–17 years, compared with CMV seropositive and seronegative healthy control donors.

Results

Humoral responses to CMV antigens (lysate, gB, IE-1) remain elevated in the patients (P < 0.0001) despite the long duration of ART. Patient’s NK cells responded poorly to K562 cells when assessed by CD107a and IFNγ, but this could not be attributed to CMV as responses were low in CMV-seronegative controls. Moreover HIV (and not CMV) increased expression of CD57 on CD56^lo cells.

Conclusions

Comparisons with published studies suggest that CMV accelerates age-related increases in CD57 expression but levels plateau by 60–70 years of age, so the effect of CMV disappears. In HIV patients the plateau is higher and perhaps reached sooner.

     

What Is Behavioural Medicine? Commentary on Definition Proposed by Dekker,Stauder and Penedo

Purpose

Dekker et al. (2016) propose an updated definition of behavioural medicine.

Method

In this commentary, we discuss how the field and the disciplines involved have changed over time before suggesting small amendments to the proposed definition.

Results

We suggest that the range of medicine which might be considered ‘behavioural’ is increasing to encompass virtually all medical practice. In addition, the role of behaviour and the potential for behaviour change as a means of improving health have become increasingly important. A defining characteristic of behavioural medicine is the involvement of multiple disciplines, working together or in parallel and, as the extent of the field expands, more disciplines are likely to be involved.

Conclusion

We therefore propose that the definition should represent the full width of the research, practice and disciplines involved in behavioural medicine.

     

Impact of tuberculosis on mortality among HIV-infected patients receiving antiretroviral therapy in Uganda: a prospective cohort analysis

Background

Tuberculosis (TB) disease affects survival among HIV co-infected patients on antiretroviral therapy (ART). Yet, the magnitude of TB disease on mortality is poorly understood.

Methods

Using a prospective cohort of 22,477 adult patients who initiated ART between August 2000 and June 2009 in Uganda, we assessed the effect of active pulmonary TB disease at the initiation of ART on all-cause mortality using a Cox proportional hazards model. Propensity score (PS) matching was used to control for potential confounding. Stratification and covariate adjustment for PS and not PS-based multivariable Cox models were also performed.

Results

A total of 1,609 (7.52%) patients had active pulmonary TB at the start of ART. TB patients had higher proportions of being male, suffering from AIDS-defining illnesses, having World Health Organization (WHO) disease stage III or IV, and having lower CD4 cell counts at baseline (p?<?0.001). The percentages of death during follow-up were 10.47% and 6.38% for patients with and without TB, respectively. The hazard ratio (HR) for mortality comparing TB to non-TB patients using 1,686 PS-matched pairs was 1.37 (95% confidence interval [CI]: 1.08 – 1.75), less marked than the crude estimate (HR?=?1.74, 95% CI: 1.49 – 2.04). The other PS-based methods and not PS-based multivariable Cox model produced similar results.

Conclusions

After controlling for important confounding variables, HIV patients who had TB at the initiation of ART in Uganda had an approximate 37% increased hazard of overall mortality relative to non-TB patients.

     

Factors Associated With Insulin Resistance in Adults With HIV Receiving Contemporary Antiretroviral Therapy: a Brief Update

Purpose of Review

This narrative review summarizes recent data on factors associated with insulin resistance (IR) in adults with HIV, including contemporary antiretroviral therapy (ART).

Recent Findings

IR remains common in persons with HIV, even those receiving contemporary ART. Generalized and abdominal obesity and ectopic fat are correlates of IR, and emerging data have identified associations with biomarkers of inflammation and immune activation. Small studies suggest associations between mitochondria and IR. In ART-naïve individuals, IR increased within 4 weeks of starting ART in persons receiving contemporary boosted protease inhibitors or an integrase inhibitor.

Summary

The importance of IR in non-diabetic persons with HIV will continue to grow as the population ages and obesity increases. Non-invasive estimates of IR appear to perform well in persons with HIV, but clinically relevant cutoffs are uncertain. Unexpected metabolic effects of newer HIV integrase inhibitors have been reported; thus, careful observation for and studies of IR are still warranted.

     

Key challenges in simulated patient programs: An international comparative case study

Background

The literature on simulated or standardized patient (SP) methodology is expanding. However, at the level of the program, there are several gaps in the literature. We seek to fill this gap through documenting experiences from four programs in Australia, Canada, Switzerland and the United Kingdom. We focused on challenges in SP methodology, faculty, organisational structure and quality assurance.

Methods

We used a multiple case study method with cross-case synthesis. Over eighteen months during a series of informal and formal interactions (focused meetings and conference presentations) we documented key characteristics of programs and drew on secondary document sources.

Results

Although programs shared challenges in SP methodology they also experienced differences. Key challenges common to programs included systematic quality assurance and the opportunity for research. There were differences in the terminology used to describe SPs, in their recruitment and training. Other differences reflected local conditions and demands in organisational structure, funding relationships with the host institution and national trends, especially in assessments.

Conclusion

This international case study reveals similarities and differences in SP methodology. Programs were highly contextualised and have emerged in response to local, institutional, profession/discipline and national conditions. Broader trends in healthcare education have also influenced development. Each of the programs experienced challenges in the same themes but the nature of the challenges often varied widely.

     

Hygiene Behaviour and Associated Factors among In-School Adolescents in Nine African Countries

Background

This report examines hygiene behaviour and associated factors among 13-15 year old in-school adolescents in nine African countries.

Purpose

The total sample included 25,760 school children aged 13-15 years from nationally representative samples from nine African countries.

Method

We examined the prevalence of and relationship between tooth brushing, hand washing before eating, hand washing after toileting, hand washing with soap and a range of psychosocial factors such as socio-demographic characteristics, health behaviour, mental health or well-being and protective factors.

Results

Overall, sub-optimal hygiene behaviour was reported, the proportions of school children reporting optimal (>once a day) tooth brushing (77.3%) was higher than the proportions reported for washing their hands regularly before meals (62.2%), after toileting (58.4%) and washing their hands with soap (35.0%). In multivariate analysis higher education, health-enhancing behaviours such as daily fruits or vegetable consumption, and protective factors such as caregiver supervision were associated with tooth brushing, hand washing before meals, hand washing after toileting and washing of hands with soap.

Conclusion

The cross-national data on hygiene behaviour from nine African countries found sub-optimal hygiene behaviour. Various determinants of optimal hygiene behaviour were identified that can guide programmes to improve hygiene behaviour of this adolescent population.

     

eHealth for Stigma Reduction Efforts Designed to Improve Engagement in Care for People Living with HIV

Purpose of Review

HIV-related stigma remains a significant barrier to engagement in care for persons living with HIV (PLWH) worldwide. This review examines the use of eHealth technologies for reducing stigma as a pathway toward improved engagement in care for PLWH. We provide a brief overview of effective stigma reduction interventions for PLWH, both eHealth and others; identify gaps in the research on use of eHealth technologies for stigma reduction; and suggest potential research avenues moving forward.

Recent Findings

The majority of HIV-related eHealth studies use technology to improve ART adherence. To date, few HIV-related eHealth studies have included any measurement of stigma.

Summary

Given the current narrow evidence base, further research is needed to determine whether eHealth technologies can help to reduce stigma and improve engagement in care for PLWH.

     

The effect of Tenofovir on renal function among Ugandan adults on long-term antiretroviral therapy: a cross-sectional enrolment analysis

Background

WHO recommends using Tenofovir containing first line antiretroviral therapy (ART), however, Tenofovir has been reported to be associated with renal impairment and dysfunction. We compared renal function among individuals on Tenofovir and those on non-Tenofovir containing ART.

Methods

In a cross-sectional study of HIV-Positive adults on ART, at enrolment into a prospective cohort to study the long-term complications of ART in Uganda, information on biophysical measurements, medical history, clinical examination and renal function tests (RFTs) was collected. Fractional Tubular phosphate reabsorption and estimated glomerular filtration rate (eGFR) were calculated. Mean values of RFTs and proportions with abnormal RFTs were compared between non-Tenofovir containing (Non-TDF) and Tenofovir containing (TDF-ART) ART regimen groups using a general linear regression model. Durations of TDF exposure were also compared.

Results

Between July 2013 and October 2014, we enrolled 953 individuals on ART for 6 or more months, median duration on ART was 9.3 years, 385 (40.4 %) were on non-TDF and 568 (59.6 %) on TDF-ART regimens. The proportion of participants with Proteinuria (>30 mg/dl) was higher among the TDF-ART group than the non-TDF ART group. However, in multivariable analysis, there were no significant differences in the adjusted mean differences of eGFR, serum urea, serum creatinine, fractional tubular reabsorption of phosphate and serum phosphates when patients on TDF-ART were compared with those on non-TDF containing ART. There were no differences in renal function even when different durations on Tenofovir were compared.

Conclusions

We found no differences in renal function among patients on Tenofovir and non-Tenofovir containing ART for almost a decade. Tenofovir based first line ART can therefore safely be initiated even in settings without routine renal function monitoring.

     

Plasma HIV-1 RNA viral load rebound among people who inject drugs receiving antiretroviral therapy (ART) in a Canadian setting: an ethno-epidemiological study

Background

People who inject drugs (PWID) living with HIV often experience sub-optimal antiretroviral therapy (ART) treatment outcomes, including HIV plasma viral load (PVL) rebound. While previous studies have identified risk factors for PVL rebound among PWID, no study has examined the perspectives of PWID who have experienced PVL rebound episodes. We conducted an ethno-epidemiological study to investigate the circumstances surrounding the emergence of rebound episodes among PWID in Vancouver, BC, Canada.

Methods

Comprehensive clinical records linked to a community-based prospective observational cohort of HIV-positive drug users were used to identify PWID who had recently experienced viral rebound. In-depth qualitative interviews with 16 male and 11 female participants explored participant perspectives regarding the emergence of viral rebound. A timeline depicting each participant’s HIV viral load and adherence to ART was used to elicit discussion of circumstances surrounding viral rebound.

Findings

Viral rebound episodes were shaped by interplay between various individual, social, and environmental factors that disrupted routines facilitating adherence. Structural-environmental influences resulting in non-adherence included housing transitions, changes in drug use patterns and intense drug scene involvement, and inadequate care for co-morbid health conditions. Social-environmental influences on ART adherence included poor interactions between care providers and patients producing non-adherence, and understandings of HIV treatment that fostered intentional treatment discontinuation.

Conclusions

This study describes key pathways which led to rebound episodes among PWID receiving ART and illustrates how environmental forces may increase vulnerability for non-adherence leading to treatment failure. Our findings have potential to help inform interventions and supports that address social-structural forces that foster non-adherence among PWID.

     

Varied sensitivity to therapy of HIV-1 strains in CD4<Superscript>+</Superscript> lymphocyte sub-populations upon ART initiation

Background

Although antiretroviral therapy (ART) has proven its success against HIV-1, the long lifespan of infected cells and viral latency prevent eradication. In this study we analyzed the sensitivity to ART of HIV-1 strains in naïve, central memory and effector memory CD4⁺ lymphocyte subsets.

Methods

From five patients cellular HIV-1 infection levels were quantified before and after initiation of therapy (2-5 weeks). Through sequencing the C2V3 region of the HIV-1 gp120 envelope, we studied the effect of short-term therapy on virus variants derived from naïve, central memory and effector memory CD4⁺ lymphocyte subsets.

Results

During short-term ART, HIV-1 infection levels declined in all lymphocyte subsets but not as much as RNA levels in serum. Virus diversity in the naïve and central memory lymphocyte populations remained unchanged, whilst diversity decreased in serum and the effector memory lymphocytes. ART differentially affected the virus populations co-circulating in one individual harboring a dual HIV-1 infection. Changes in V3 charge were found in all individuals after ART initiation with increases within the effector memory subset and decreases found in the naïve cell population.

Conclusions

During early ART virus diversity is affected mainly in the serum and effector memory cell compartments. Differential alterations in V3 charge were observed between effector memory and naïve populations. While certain cell populations can be targeted preferentially during early ART, some virus strains demonstrate varied sensitivity to therapy, as shown from studying two strains within a dual HIV-1 infected individual.

     

Novel Mutation in <Emphasis Type="Italic">CECR1</Emphasis> Leads to Deficiency of ADA2 with Associated Neutropenia

Purpose

Adenosine deaminase 2 (ADA2) have been reported to cause vasculitic diseases and immunodeficiency recently. Patients present with stroke episodes and rashes mimicking polyarteritis nodosa (PAN). We report a patient who has been followed up with severe neutropenia and found an unexpectedly revealed novel mutation in CECR1 affecting ADA2.

Methods

We reviewed medical records and clinical history of the patient. No mutations in other known neutropenia genes such as ELA, G6PC3, HAX1, AP3B1, LAMTOR2, VPS13B, VPS45, GFI1, JAGN1, or WAS could be detected. Sanger sequencing was used to confirm the genetic variants in the patient and relatives.

Results

Genetic analysis by exome sequencing revealed a novel mutation in the gene CECR1 (c.G962A; p.G321E) which segregated perfectly in the relatives.

Conclusion

This is the first DADA2 patient presenting with severe neutropenia. We suggest that in patients with unexplained cytopenias combined with immunodeficiency, fevers of unknown origin and high inflammation markers, DADA2 should be considered.

     

The Fat of the Matter: Obesity and Visceral Adiposity in Treated HIV Infection

Purpose of Review

The aim of this review is to summarize knowledge of the prevalence, relevant physiology, and consequences of obesity and visceral adiposity in HIV-infected adults, including highlighting gaps in current knowledge and future research directions.

Recent Findings

Similar to the general population, obesity prevalence is increasing among HIV-infected persons, and obesity and visceral adiposity are associated with numerous metabolic and inflammatory sequelae. However, HIV- and antiretroviral therapy (ART)-specific factors may contribute to fat gain and fat quality in treated HIV infection, particularly to the development of visceral adiposity, and sex differences may exist.

Summary

Obesity and visceral adiposity commonly occur in HIV-infected persons and have significant implications for morbidity and mortality. Future research should aim to better elucidate the HIV- and ART-specific contributors to obesity and visceral adiposity in treated HIV infection, with the goal of developing targeted therapies for the prevention and treatment of obesity and visceral adiposity in the modern ART era.

     

Glücklich als Paar – glücklicher Schlaf?

Background

Millions of people share a bed with their partner. Sleep und relationship could possibly influence each other.

Objectives

To identify and discuss connections between relationship and sleep quality.

Methods

Review of the literature in electronic databases.

Results

Conflict and violence in relationships lead to decreases in both partners’ sleep quality. Constructive approaches to resolving conflicts is necessary for good sleep, and vice versa. Women prefer partners with sleep-wake rhythms matching their own and report higher relationship satisfactions when the couple’s chronotypes are compatible.

Conclusions

Sleep and circadian rhythms play important roles in relationships. When treating insomnia, the relationship and the partner’s sleep should be taken into account.

     

Continued Interest and Controversy: Vitamin D in HIV

Purpose of Review

Vitamin D (VitD) deficiency is highly prevalent among HIV-infected individuals. Given the overlapping risk for several chronic disease and immunomodulatory outcomes from both long-standing HIV and VitD deficiency, there is great interest in clarifying the clinical role of VitD for this population.

Recent Findings

Recent studies have expanded our knowledge regarding the epidemiology and mechanisms of VitD deficiency-associated outcomes in the setting of HIV. Clinical trials focusing on VitD supplementation have demonstrated a positive impact on bone mineral density in subgroups of HIV-infected individuals initiating ART or on suppressive ART regimens; however, significant heterogeneity exists between studies and data are less consistent with other clinical outcomes.

Summary

Further research is needed to clarify uncertainly in several domains, including identifying patients at greatest risk for poor outcomes from VitD deficiency, standardizing definitions and measurement techniques, and better quantifying the benefits and risks of VitD supplementation across different demographic strata for skeletal and extra-skeletal outcomes.

     

Inflammatory myofibroblastic tumor of the lacrimal gland: case report of an exceptional location

Background

Inflammatory myofibroblastic tumour (IMT) is a mesenchymal neoplasm of intermediate biological potential that may affect a wide range of anatomic sites but has a particular predilection for the lung and intra-abdominal soft tissues.

Case presentation

We report here an exceptional case of inflammatory myofibroblastic tumor arising in the lacrimal gland and presenting as an orbital mass in a 24-year-old male.

Conclusion

This report aims to discuss the importance of histopathological and immunohistochemical findings in arriving at the diagnosis, which helps dictate the management, treatment and prognosis of the patient.

     

Prevalence of persistent median artery in carpal tunnel syndrome: sonographic assessment

Purpose

This study investigated the frequency of persistent median artery (PMA) in patients with carpal tunnel syndrome (CTS) and controls.

Methods

A total of 84 CTS patient wrists, and 136 wrists of control subjects without CTS, were examined on ultrasonography (US) and color Doppler US (CDUS), and by electrophysiological evaluations. The frequency of PMA in CTS was evaluated.

Results

Of 84 CTS patient wrists, 2 (2.4 %) had a PMA (both on the right side). Of 136 control wrists, 12 (9 %) had a PMA, which was unilateral in eight (three right and five left), and bilateral in two, cases. There was no significant difference between the CTS patient and control groups with respect to the frequency of PMA (P > 0.05).

Conclusions

There was no significant difference between the CTS patient and control groups in the frequency of PMA. We suggest that an ipsilateral PMA does not increase the risk of CTS.