Archive for July, 2016

Which HIV patients should be screened for osteoporosis: an international perspective

Current Opinion In HIV and AIDS May 2016 V.11 N.3 P.268–276

Alvarez, Elena; Belloso, Waldo H.; Boyd, Mark A

aHIV Molecular Research Group, School of Medicine, University College Dublin, Dublin, Ireland

bInfectious Diseases and Clinical Pharmacology Sections, Internal Medicine Service, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina

cThe Kirby Institute for Infection and Immunity in Society, University of New South Wales, Sydney, Australia

dSchool of Medicine, Hacettepe University, Ankara, Turkey

eDepartment of Infectious Diseases at Peking Union Medical College Hospital, Beijing, China

fInfectious Diseases Institute (IDI) HIV outpatient clinic at Mulago Hospital Complex, Makerere University College of Health Sciences, Kampala, Uganda

gMoscow Regional AIDS Centre, Moscow, Russia

hInfectious Diseases Unit Hospital Clinic – Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain

iICH Study Center, Hamburg, Germany

jToronto General Research Institute (TGRI), University Health Network (NHN), Toronto General Hospital, Toronto, Canada

kDivision of Endocrinology, Diabetes & Metabolism, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

lMater Misericordiae University Hospital, Department of Infectious Diseases, Dublin, Ireland

Purpose of review

This review provides international insights into the real-world clinical approach to screening for bone mineral density (BMD) and osteoporosis in people living with HIV (PLWH) using opinions from HIV physicians from key regions around the world.

Recent findings

Although a significant proportion of PLWH are aged over 50, the relative importance of low BMD to clinical care differs significantly between countries and regions, based on factors such as the population at risk, access to adequate screening resources, and physicians’ knowledge. Generally, management of osteoporosis in PLWH follows similar principals as for the general population, with risk factors for fracture combined with measurement of BMD by dual energy X-ray absorptiometry in algorithms such as Fracture Risk Assessment Tool, designed to provide an overall risk estimation. Although in most regions age is considered among the most important factors contributing to low BMD and fractures, considerable country and region-specific factors become apparent, such as malnutrition, inactivity and impact of comorbidities, substance abuse, and increasing use of tenofovir disoproxil fumarate.

Summary

These opinions highlight the diversity that still exists in the approach to the long-term management of PLWH and highlight challenges facing development of consensus guidelines that can be effectively implemented worldwide.

FULL TEXT

http://journals.lww.com/co-hivandaids/Fulltext/2016/05000/Which_HIV_patients_should_be_screened_for.5.aspx

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July 31, 2016 at 9:33 pm

How to predict the risk of fracture in HIV?

Current Opinion In HIV and AIDS May 2016 V.11 N.3 P.261–267

Yin, Michael T.; Falutz, Julian

aDivision of Infectious Diseases, Columbia University Medical Center, New York, New York, USA

bChronic Viral Illness Service, Division of Infectious Diseases, McGill University Health Center, Montreal, Quebec, Canada

Purpose of review

Skeletal fractures are more common in HIV, and impact the medical, functional and economic status of frequently vulnerable patients. Identifying asymptomatic patients with low bone mineral density (BMD)/osteoporosis requiring intervention can be expected to reduce fracture risk and complications. Clinical tools are available to determine fracture risk in the general population and are being evaluated in HIV patients. The FRAX® calculator, incorporating demographics and risk factors for osteoporosis, with or without BMD results, has been investigated most often in HIV patients.

Recent findings

The few published studies that have calculated the 10-year FRAX® risk for both major osteoporosis and hip fractures without BMD generally show limited precision in predicting the presence of osteoporosis severe enough to initiate treatment. It remains uncertain whether using HIV as a secondary risk factor and adding dual X-ray absorptiometry (DXA)-BMD information improves case-finding compared with using DXA results only. Not incorporating risks relevant to aging HIV patients such as antiretroviral exposure, hepatitis C virus coinfection and history of falls is other potential limitation.

Summary

Accurate screening tools using clinical risk factors alone to determine fracture risk in HIV are not yet available. Further research and validation studies are necessary.

FULL TEXT

http://journals.lww.com/co-hivandaids/Fulltext/2016/05000/How_to_predict_the_risk_of_fracture_in_HIV_.4.aspx

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July 31, 2016 at 9:32 pm

Does systemic inflammation and immune activation contribute to fracture risk in HIV?

Current Opinion In HIV and AIDS May 2016 V.11 N.3 P.253–260

McGinty, Tara; Mirmonsef, Paria; Mallon, Patrick W.G.

aHIV Molecular Research Group, School of Medicine, University College Dublin

bDepartment of Infectious Diseases, Mater Misericordiae University Hospital, Dublin, Ireland

cDepartment of Immunology/Microbiology, Rush University Medical Center, Chicago, Illinois, USA

*Tara McGinty and Paria Mirmonsef have contributed equally to the writing of this article.

Purpose of review

There is increasing evidence pointing toward an important role of heightened immune activation and inflammation in people living with HIV contributing to the development of non-AIDS comorbidities. This review aims to explore low bone mineral density (BMD) in HIV with a focus on the underlying mechanisms and relationships between the immune and skeletal systems.

Recent findings

Baseline immune activation and inflammation negatively impact BMD at antiretroviral therapy (ART) initiation. B- and T-cell alterations in HIV lead to an imbalance in the osteoblastic osteoprotegerin (OPG) and osteoclastic receptor activator of NF-κB ligand (RANKL) cytokines which favours osteoclastogenesis and bone resorption. These findings suggest an important role for immune-mediated mechanisms in the pathogenesis of low BMD in HIV.

Summary

Bone homeostasis is in part regulated by cells of the immune system through complex interactions with the RANK/RANKL/OPG Disturbances in the normal functioning of T, B cells, and monocytes in HIV and the resulting proinflammatory state may contribute to dysregulation of this finely controlled balance leading to increased bone loss. Pre-ART levels of immune activation and inflammation have a consistently negative effect on BMD and further suggest the immunocentric basis of bone loss in HIV alongside supporting the benefits of earlier ART initiation. Further longitudinal studies will help determine the effect this will have on fracture risk in people living with HIV.

FULL TEXT

http://journals.lww.com/co-hivandaids/Fulltext/2016/05000/Does_systemic_inflammation_and_immune_activation.3.aspx

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July 31, 2016 at 9:30 pm

Working towards an understanding of bone disease in HIV

Current Opinion In HIV and AIDS May 2016 V.11 N.3 P.251–252

Editorial

Brown, Todd T.; Mallon, Patrick W.G.

aDivision of Endocrinology, Diabetes, and Metabolism, Johns Hopkins University, Baltimore, Maryland, USA

bHIV Molecular Research Group, School of Medicine, University College Dublin, Dublin, Ireland

Over the next 15 years, the population of older people living with HIV is expected to increase markedly. In the Dutch ATHENA cohort, for example, the proportion of HIV-infected persons 60 years and older will increase from 8% in 2010 to 39% in 2030, with expected increases in aging-related comorbidities [1]. Osteoporotic fracture is a quintessential disease of aging whose incidence increases exponentially after age 65–70 years in the general population. It is also a major cause of morbidity, mortality, reduced quality of life, and healthcare expenditure…

FULL TEXT

http://journals.lww.com/co-hivandaids/Fulltext/2016/05000/Editorial___Working_towards_an_understanding_of.2.aspx

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July 31, 2016 at 12:30 pm

Strategies for targeting residual HIV infection

Current Opinion In HIV and AIDS July 2016 V.11 N.4 P.359–361

Chomont, Nicolas; Perreau, Matthieu

aCentre de Recherche du CHUM

bDepartment of Microbiology, Infectious Diseases and Immunology, Université de Montréal, Montréal, Quebec, Canada

cDivision of Immunology and Allergy, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland

Seven years ago, Hutter et al.[1] reported the unique case of a 40-year-old HIV-infected man who was cured of HIV infection following an allogeneic bone marrow transplant. Timothy Ray Brown, also known as the ‘Berlin Patient’ is until today the only person from whom HIV has been eradicated. This extraordinary and largely unexpected success fostered HIV cure research by opening novel therapeutic possibilities that could potentially surpass combination antiretroviral therapy (ART). Indeed, although ART has dramatically reduced the death rate from AIDS and improved the quality of life of many HIV-infected individuals, the possible long-term toxicity associated with ART, stigma and cost all contribute to the necessity of finding a cure….

FULL TEXT

http://journals.lww.com/co-hivandaids/Fulltext/2016/07000/Strategies_for_targeting_residual_HIV_infection.2.aspx

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July 31, 2016 at 12:29 pm

Current approaches to assess HIV-1 persistence

Current Opinion In HIV and AIDS July 2016 V.11 N.4 P. 424–431

Banga, Riddhima; Procopio, Francesco A.; Perreau, Matthieu

Division of Immunology and Allergy, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland

Purpose of review

The persistence of HIV within long-lived HIV-infected CD4+ T cells is the primary obstacle towards HIV eradication and numerous strategies are currently being evaluated to target and kill HIV-infected cells to ultimately find a cure. HIV reservoirs are classically quantified by standard methods such as integrated HIV DNA (Alu PCR) and/or quantitative viral outgrowth assay; however, recent technical advances may offer new opportunities to comprehensively assess the impact of clinical interventions.

Recent findings

Digital droplet PCR, tat/rev-induced limiting dilution analysis, enhanced quantitative viral outgrowth assay, and whole genome sequencing technologies offer increased precision and/or higher sensitivity to quantify and characterize HIV reservoirs in antiretroviral therapy-treated HIV-infected patients.

Summary

The objective of this review is to highlight the characteristics and limits of recent technical advances that may help to monitor the impact of clinical interventions in antiretroviral therapy-treated patients.

FULL TEXT

http://journals.lww.com/co-hivandaids/Fulltext/2016/07000/Current_approaches_to_assess_HIV_1_persistence.12.aspx

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July 31, 2016 at 12:27 pm

Persistent HIV-1 replication during antiretroviral therapy

Current Opinion In HIV and AIDS July 2016 V.11 N.4 P.417–423

Martinez-Picado, Javier; Deeks, Steven G

aAIDS Research Institute IrsiCaixa, Institut d’Investigació en Ciències de la Salut Germans Trias i Pujol (IGTP), Universitat Autònoma de Barcelona, Badalona

bUniversity of Vic-Central University of Catalonia (UVic-UCC), Vic

cInstitució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain

dDepartment of Medicine, University of California, San Francisco, California, USA

Purpose of review

The present review will highlight some of the recent findings regarding the capacity of HIV-1 to replicate during antiretroviral therapy (ART).

Recent findings

Although ART is highly effective at inhibiting HIV replication, it is not curative. Several mechanisms contribute to HIV persistence during ART, including HIV latency, immune dysfunction, and perhaps persistent low-level spread of the virus to uninfected cells (replication). The success in curing HIV will depend on efficiently targeting these three aspects. The degree to which HIV replicates during ART remains controversial. Most studies have failed to find any evidence of HIV evolution in blood, even with samples collected over many years, although a recent very intensive study of three individuals suggested that the virus population does shift, at least during the first few months of therapy. Stronger but still not definitive evidence for replication comes from a series of studies in which standard regimens were intensified with an integration inhibitor, resulting in changes in episomal DNA (blood) and cell-associated RNA (tissue). Limited drug penetration within tissues and the presence of immune sanctuaries have been argued as potential mechanisms allowing HIV to spread during ART. Mathematical models suggest that HIV replication and evolution is possible even without the selection of fully drug-resistant variants. As persistent HIV replication could have clinical consequences and might limit the efficacy of curative interventions, determining if HIV replicates during ART and why, should remain a key focus of the HIV research community.

Summary

Residual viral replication likely persists in lymphoid tissues, at least in a subset of individuals. Abnormal levels of immune activation might contribute to sustain virus replication.

FULL TEXT

http://journals.lww.com/co-hivandaids/Fulltext/2016/07000/Persistent_HIV_1_replication_during_antiretroviral.11.aspx

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July 29, 2016 at 7:17 pm

Strategies to target HIV-1 in the central nervous system

Current Opinion In HIV and AIDS July 2016 V.11 N.4

Gray, Lachlan R.; Brew, Bruce J.; Churchill, Melissa J.

Strategies to target HIV-1 in the central nervous system

Gray, Lachlan R.; Brew, Bruce J.; Churchill, Melissa J.

aCenter for Biomedical Research, Burnet Institute

bDepartment of Infectious Diseases, Monash University, Melbourne, Victoria

cDepartments of Neurology, Immunology and Infectious Diseases and Peter Duncan Neurosciences Unit, St Vincent’s Centre for Applied Medical Research, St Vincent’s Hospital, Sydney, New South Wales

dDepartment of Microbiology, Monash University, Clayton, Victoria

eDepartment of Medicine, Monash University, Melbourne, Victoria, Australia

Purpose of review

To review current knowledge of viral reservoirs in the central nervous system (CNS) and identify the CNS-specific barriers and strategies to cure human immunodeficiency virus type 1 (HIV-1) within the brain.

Recent findings

The cumulative data of HIV-1 infection of the CNS support the ability of the CNS to act as a viral reservoir for HIV-1. The HIV-1 viral strains found in the CNS are distinct to those found in other parts of the body. These differences have been well documented for env and also extend to the viral promoter, the long terminal repeat, and influence the ability of the virus to replicate, establish latency and respond to latency-reversing agents (LRAs). In addition, the bioavailability and activity of LRAs and antiretrovirals within the CNS suggest altered properties compared with the blood, which may influence their effectiveness. Selected LRAs were shown to have reduced effectiveness against CNS-derived viral strains compared with blood-derived strains from the same patients. Finally, altered immune surveillance within the CNS may also interfere with the efficiency of cure strategies within this compartment.

Summary

Together, these data suggest that the CNS viral reservoir is unique and presents a distinct set of challenges that need to be overcome to ensure successful viral elimination within this compartment. Future studies will need to develop CNS-active LRAs and biomarkers to enable monitoring and evaluation of treatment outcomes within the CNS during HIV-1 cure clinical trials.

FULL TEXT

http://journals.lww.com/co-hivandaids/Fulltext/2016/07000/Strategies_to_target_HIV_1_in_the_central_nervous.4.aspx

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July 29, 2016 at 7:15 pm

Surviving Severe Sepsis: Is That Enough?

Critical Care Medicine August 2016 V.44 N.8 P.1603–1604

Editorials

Anderson-Shaw, Lisa

Department of Clinical Ethics Consult Service, UI Health, University of Illinois at Chicago, Chicago, IL

Sepsis and severe forms of sepsis is a frequent diagnosis in the ICU setting. “Sepsis is one of the oldest and most elusive syndromes in medicine” (1). The definition of severe sepsis includes a systemic inflammatory response to infection complicated by acute organ dysfunction (1). “Over 1,665,000 cases of sepsis occur in the United States each year, with a mortality rate up to 50%” (2). In the ICU setting survival of severe sepsis is a primary goal, however, quality-of-life (QoL) issues for these patients after discharge is of great concern to the patient and to their family and physicians who will be providing the follow-up care that may be complex and ongoing (3). Long after hospitalization, survivors of severe sepsis experience an impaired QoL and an ongoing feeling that they may be imposing a burden of care to their family and loved ones. This is especially true for survivors who where physically independent prior to severe sepsis, but after discharge are left with dependence on others in daily activities. Although the goal of care in the ICU setting is appropriately to cure sepsis and minimize morbidity, it may be that many survivors are not getting the ongoing care required for their complex physical, psychological, and emotional needs after discharge. A recent study reported that after 6 months, up to 80% of severe sepsis/septic shock survivors stopped coming to their follow-up consultations (4). It is important to study QoL for survivors of sepsis in order to provide patient-centered care and to assess goals of care frequently so survivors and their families are offered holistic care and are not lost to follow-up…..

abstract

http://journals.lww.com/ccmjournal/Fulltext/2016/08000/Surviving_Severe_Sepsis___Is_That_Enough__.16.aspx

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July 29, 2016 at 2:30 pm

Sepsis-3: What is the Meaning of a Definition?

Critical Care Medicine August 2016 V.44 N.8 P.1459–1460

Marshall, John C.

Departments of Surgery and Critical Care Medicine, Keenan Research Centre for Biomedical Science of the Li Ka Shing Knowledge Institute, St. Michael’s Hospital, University of Toronto, Toronto, Ontario, Canada

The recent publication of Sepsis-3–the latest iteration of an effort to define sepsis–has evoked an impressive response (1). To date it has been viewed more than one million times on the JAMA website, making it one of the most highly accessed articles there in recent years. It has also generated a flurry of commentaries–some supportive, some opposing, and almost all thoughtful (2–4). Indeed recognizing as the original paper did that the new definition is simply the next step in the evolution of a challenging process, the controversy is as important as the Sepsis-3 document in clarifying what has been accomplished and what remains undone.According to the Merriam-Webster Dictionary, a definition is “…an explanation of the meaning of a word…”. Sepsis to the Greeks denoted a range of processes characterized by putrefaction and a foul smell (5). With the identification of the pathogenic role of microorganisms in disease, sepsis has come to take on a meaning related to the consequences of infection. This meaning has changed as our understanding of the biology of infection and the host response has evolved. In the early 1970s, Stedman’s Medical Dictionary defined sepsis as “…the presence of pus-forming organisms in the bloodstream…”, however this definition rapidly became obsolete with the discovery that the adverse sequelae of infection arose through the activation of a host response, rather than as a consequence of the intrinsic toxicity of the microorganism or its products. A new definition was needed. In 1991, a consensus conference of the SCCM and ACCP suggested that sepsis is “…the systemic host response to invasive infection …” (6). Further cognizant of the fact that an identical clinical response could be evoked by non-infectious stimuli, they proposed a neologism, the systemic inflammatory response syndrome (SIRS), to denote the response independent of its cause. Time and reflection rendered this definition inadequate…..

abstract

http://journals.lww.com/ccmjournal/Fulltext/2016/08000/Sepsis_3___What_is_the_Meaning_of_a_Definition_.1.aspx

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July 29, 2016 at 2:29 pm

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