Archive for August 2, 2016

Hepatitis C virus coinfection as a risk factor for osteoporosis and fracture

Current Opinion In HIV and AIDS May 2016 V.11 N.3 P.285–293

Bedimo, Roger; Maalouf, Naim M.; Re, Vincent Lo III

aInfectious Diseases Section, Medical Service, Veterans Affairs North Texas Healthcare System

bDivision of Infectious Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center

cEndocrine Section, Medical Service, Veterans Affairs North Texas Healthcare System

dDivision of Mineral Metabolism, Department of Internal Medicine, and the Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, Texas

eDivision of Infectious Diseases, Department of Medicine

fDepartment of Biostatistics and Epidemiology, Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA

Purpose of review

With increased survival of HIV-infected patients, osteoporotic fractures have developed as a major cause of morbidity in these patients, and chronic hepatitis C virus (HCV) coinfection has emerged as a significant contributor to this increased fracture risk. The present article reviews the epidemiologic and clinical evidence for osteoporosis and increased fracture risk among HIV/HCV coinfected patients, and potential mechanisms for these outcomes with HCV coinfection.

Recent findings

Epidemiologic studies suggest that HIV/HCV coinfected patients exhibit a three-fold increased fracture incidence compared with uninfected controls, and 1.2–2.4-fold increased fracture risk compared with HIV monoinfected patients. Recent reports suggest that chronic HCV coinfection is independently associated with reduced bone mineral density in HIV, but that it is not associated with significantly increased bone turnover. The deleterious impact of chronic HCV on BMD and fracture risk occurs even in the absence of advanced liver fibrosis or cirrhosis. New tools to assess bone quality, including the trabecular bone score, high-resolution peripheral quantitative computed tomography, and in-vivo microindentation, may help improve understanding of the mechanisms of HCV-associated skeletal fragility. The impact of approved antiosteoporosis medications and direct-acting antivirals for the treatment of chronic HCV infection on patients’ bone health remain to be studied.

Summary

Chronic HCV infection is an independent risk factor for osteoporosis and fractures among HIV-infected patients, even before the development of cirrhosis. The underlying mechanisms are being unraveled, but major questions persist regarding the optimal evaluation and management of bone health in HIV/HCV coinfected patients.

FULL TEXT

http://journals.lww.com/co-hivandaids/Fulltext/2016/05000/Hepatitis_C_virus_coinfection_as_a_risk_factor_for.7.aspx

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August 2, 2016 at 1:24 pm

Efficacy and Safety of Ceftazidime-Avibactam Plus Metronidazole Versus Meropenem in the Treatment of Complicated Intra-abdominal Infection: Results From a Randomized, Controlled, Double-Blind, Phase 3 Program.

Clin Infect Dis. 2016 Jun 1;62(11):1380-9.

Mazuski JE1, Gasink LB2, Armstrong J3, Broadhurst H3, Stone GG4, Rank D5, Llorens L5, Newell P3, Pachl J6.

Author information

1Washington University School of Medicine, St Louis, Missouri.

2AstraZeneca, Wilmington, Delaware.

3AstraZeneca, Alderley Park, United Kingdom.

4AstraZeneca, Waltham, Massachusetts.

5Actavis, Oakland, California.

6The Charles University, Prague, Czech Republic.

Abstract

BACKGROUND:

When combined with ceftazidime, the novel non-β-lactam β-lactamase inhibitor avibactam provides a carbapenem alternative against multidrug-resistant infections. Efficacy and safety of ceftazidime-avibactam plus metronidazole were compared with meropenem in 1066 men and women with complicated intra-abdominal infections from 2 identical, randomized, double-blind phase 3 studies (NCT01499290 and NCT01500239).

METHODS:

The primary end point was clinical cure at test-of-cure visit 28-35 days after randomization, assessed by noninferiority of ceftazidime-avibactam plus metronidazole to meropenem in the microbiologically modified intention-to-treat (mMITT) population (in accordance with US Food and Drug Administration guidance), and the modified intention-to-treat and clinically evaluable populations (European Medicines Agency guidance). Noninferiority was considered met if the lower limit of the 95% confidence interval for between-group difference was greater than the prespecified noninferiority margin of -12.5%.

RESULTS:

Ceftazidime-avibactam plus metronidazole was noninferior to meropenem across all primary analysis populations. Clinical cure rates with ceftazidime-avibactam plus metronidazole and meropenem, respectively, were as follows: mMITT population, 81.6% and 85.1% (between-group difference, -3.5%; 95% confidence interval -8.64 to 1.58); modified intention-to-treat, 82.5% and 84.9% (-2.4%; -6.90 to 2.10); and clinically evaluable, 91.7% and 92.5% (-0.8%; -4.61 to 2.89). The clinical cure rate with ceftazidime-avibactam plus metronidazole for ceftazidime-resistant infections was comparable to that with meropenem (mMITT population, 83.0% and 85.9%, respectively) and similar to the regimen’s own efficacy against ceftazidime-susceptible infections (82.0%). Adverse events were similar between groups.

CONCLUSIONS:

Ceftazidime-avibactam plus metronidazole was noninferior to meropenem in the treatment of complicated intra-abdominal infections. Efficacy was similar against infections caused by ceftazidime-susceptible and ceftazidime-resistant pathogens. The safety profile of ceftazidime-avibactam plus metronidazole was consistent with that previously observed with ceftazidime alone.

CLINICAL TRIALS REGISTRATION: NCT01499290 and NCT01500239.

PDF

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872289/pdf/ciw133.pdf

August 2, 2016 at 1:22 pm

The protease inhibitors and HIV-associated bone loss

Current Opinion In HIV and AIDS May 2016 V.11 N.3 P. 333–342

Moran, Caitlin A.; Weitzmann, M. Neale; Ofotokun, Ighovwerha

aDepartment of Medicine, Division of Infectious Diseases, Emory University School of Medicine

bGrady Healthcare System, Atlanta

cDepartment of Medicine, Division of Endocrinology, Metabolism & Lipids, Emory University School of Medicine, Atlanta

dAtlanta Department of Veterans Affairs Medical Center, Decatur, Georgia, USA

Purpose of review

HIV infection is an established risk factor for osteoporosis and bone fracture. Combination antiretroviral therapy (cART) increases bone resorption leading to an additional 2–6% bone mineral density (BMD) loss within the first 1–2 years of therapy. Although tenofovir disoproxil fumarate is often blamed for antiretroviral drug-associated bone loss, evidence abounds to suggest that other agents, including the protease inhibitors (PIs), have adverse bone effects. In the current review, we examine bone loss associated with protease inhibitor use, describing the relative magnitude of bone loss reported for individual protease inhibitors. We also review the potential mechanisms associated with protease inhibitor-induced bone loss.

Recent findings

As a class, protease inhibitors contribute to a greater degree of bone loss than other anchor drugs. HIV disease reversal and the associated immune reconstitution following cART initiation play an important role in protease inhibitor-mediated bone loss in addition to plausible direct effects of protease inhibitors on bone cells.

Summary

Protease inhibitors remain an important component of cART despite their adverse effects on bone. A better understanding of factors that drive HIV/cART-induced bone loss is needed to stem the rising rate of fracture in the HIV-infected population.

FULL TEXT

http://journals.lww.com/co-hivandaids/Fulltext/2016/05000/The_protease_inhibitors_and_HIV_associated_bone.12.aspx

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August 2, 2016 at 8:22 am

Tenofovir and bone health

Current Opinion In HIV and AIDS May 2016 V.11 N.3 P.326–332

Grant, Philip M.; Cotter, Aoife G.

aDivision of Infectious Diseases; Department of Medicine; Stanford University, Palo Alto, CA, USA

bHIV Molecular Research Group, School of Medicine & Medical Science, University College Dublin

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

Purpose of review

With continued improvements to the antiviral efficacy and tolerability of antiretroviral therapy, long-term safety of antiretroviral therapy has become paramount. Low bone mineral density and fragility fractures are more common in HIV-infected individuals than in the general population. The aims of this review are to describe potential mechanisms underlying the adverse effects of tenofovir on bone, clinical studies of tenofovir disoproxil fumarate (TDF) and bone, and more recent bone data on tenofovir alafenamide.

Recent finding

Several studies have demonstrated an approximately 1–3% greater bone mineral density loss with TDF compared with other agents. Recent studies with tenofovir alafenamide have shown improved bone (and renal) safety with similar virologic efficacy when compared to TDF.

Summary

Given these findings, TDF-containing regimens may be gradually replaced with non-TDF containing regimens for the treatment of HIV infection, especially in those at higher risk for fragility fracture.

FULL TEXT

http://journals.lww.com/co-hivandaids/Fulltext/2016/05000/Tenofovir_and_bone_health.11.aspx

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August 2, 2016 at 8:21 am


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