Archive for November, 2009

When to Start Antiretroviral Therapy in Resource-Limited Settings

Annals of Internal Medicine  20 Jul 2009

Rochelle P. Walensky, MD, MPH; Lindsey L. Wolf, SB; Robin Wood, FCP, MMed, DTM&H; Mariam O. Fofana, AB; Kenneth A. Freedberg, MD, MSc; Neil A. Martinson, MBBCh, MPH; A. David Paltiel, PhD; Xavier Anglaret, MD, PhD; Milton C. Weinstein, PhD; and Elena Losina, PhD, for the CEPAC-International Investigators*

From the Massachusetts General Hospital, Brigham and Women’s Hospital, Harvard University Medical School, Harvard School of Public Health, and Boston University School of Public Health, Boston, Massachusetts; University of Cape Town, Cape Town, and Perinatal HIV Research Unit, Johannesburg, South Africa; Johns Hopkins University, Baltimore, Maryland; Yale School of Medicine, New Haven, Connecticut; and Université Victor Segalen Bordeaux 2, Bordeaux, France.

Background: The results of international clinical trials that are assessing when to initiate antiretroviral therapy (ART) will not be available for several years.

Objective: To inform HIV treatment decisions about the optimal CD4 threshold at which to initiate ART in South Africa while awaiting the results of these trials.

Design: Cost-effectiveness analysis by using a computer simulation model of HIV disease.

Data Sources: Published data from randomized trials and observational cohorts in South Africa.

Target Population: HIV-infected patients in South Africa.

Time Horizon: 5-year and lifetime.

Perspective: Modified societal.

Intervention: No treatment, ART initiated at a CD4 count less than 0.250 x 109 cells/L, and ART initiated at a CD4 count less than 0.350 x 109 cells/L.

Outcome Measures: Morbidity, mortality, life expectancy, medical costs, and cost-effectiveness.

Results of Base-Case Analysis: If 10% to 100% of HIV-infected patients are identified and linked to care, a CD4 count threshold for ART initiation of 0.350 x 109 cells/L would reduce severe opportunistic diseases by 22 000 to 221 000 and deaths by 25 000 to 253 000 during the next 5 years compared with ART initiation at 0.250 x 109 cells/L; cost increases would range from $142 million (10%) to $1.4 billion (100%). Either ART initiation strategy would increase long-term survival by at least 7.9 years, with a mean per-person life expectancy of 3.8 years with no ART and 12.5 years with an initiation threshold of 0.350 x 109 cells/L. Compared with an initiation threshold of 0.250 x 109 cells/L, a threshold of 0.350 x 109 cells/L has an incremental cost-effectiveness ratio of $1200 per year of life saved.

Results of Sensitivity Analysis: Initiating ART at a CD4 count less than 0.350 x 109 cells/L would remain cost-effective over the next 5 years even if the probability that the trial would demonstrate the superiority of earlier therapy is as low as 17%.

Limitation: This model does not consider the possible benefits of initiating ART at a CD4 count greater than 0.350 x 109 cells/L or of reduced HIV transmission.

Conclusion: Earlier initiation of ART in South Africa will probably reduce morbidity and mortality, improve long-term survival, and be cost-effective. While awaiting trial results, treatment guidelines should be liberalized to allow initiation at CD4 counts less than 0.350 x 109 cells/L, earlier than is currently recommended.

Primary Funding Source: National Institute of Allergy and Infectious Diseases and the Doris Duke Charitable Foundation.

abstract

http://www.annals.org/cgi/content/abstract/0000605-200908040-00138v1?papetoc

PDF

http://www.annals.org/cgi/reprint/0000605-200908040-00138v1.pdf

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November 30, 2009 at 11:43 pm Leave a comment

Clinical management of human infection with pandemic (H1N1) 2009

WHO World Health Organization

November 2009

Revised guidance OMS

Introduction

A novel influenza A (H1N1) virus of swine origin emerged among people in Mexico during the spring of 2009 and spread with travellers worldwide, resulting in the first influenza pandemic since 1968. As of October 2009, 195 countries have reported confirmed human cases of pandemic (H1N1) 2009. While the majority of illnesses caused by pandemic (H1N1) 2009 virus infection have been self-limited mild-to-moderate uncomplicated disease, severe complications including fatal outcomes have been reported….

PDF

http://www.who.int/csr/resources/publications/swineflu/clinical_management_h1n1.pdf

November 30, 2009 at 5:58 pm Leave a comment

The Emergency Use Authorization of Peramivir for Treatment of 2009 H1N1 Influenza

N Engl J of Medicine Nov. 2009

Debra Birnkrant, M.D., and Edward Cox, M.D., M.P.H.

On October 23, 2009, Food and Drug Administration (FDA) Commissioner Margaret Hamburg issued an Emergency Use Authorization (EUA) for peramivir for intravenous injection (BioCryst Pharmaceuticals). Peramivir is an unapproved investigational neuraminidase inhibitor that may be effective in treating certain hospitalized adult and pediatric patients with suspected or confirmed cases of 2009 H1N1 influenza. The EUA allows health care providers to use peramivir, subject to specified conditions. This is the first EUA that has been issued for an unapproved drug.

The legal standard for the authorization of an EUA during a declared public health emergency requires a finding that it is “reasonable to believe” that the product “may be effective,” as well as a finding that its known and potential benefits outweigh its known and potential risks.1 There must also be no other adequate, approved, and available treatment alternatives for the specific indication. This is a lower evidentiary standard than that used for marketing approval, which requires a finding of “substantial evidence” of efficacy for the proposed use based on adequate and well-controlled trials, as well as a robust safety evaluation…

Abstract

http://content.nejm.org/cgi/content/full/NEJMp0910479?query=TOC

PDF

http://content.nejm.org/cgi/reprint/NEJMp0910479v2.pdf

November 30, 2009 at 5:49 pm Leave a comment

Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents -November 3, 2008

Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents -November 3, 2008

Developed by the DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents – A Working Group of the Office of AIDS Research Advisory Council (OARAC)

http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf

November 30, 2009 at 12:41 pm Leave a comment

CD4+ Count–Guided Interruption of Antiretroviral Treatment

N Engl J of Medicine  No.30, 2006  V.355  N.22  p.2283-2296

The Strategies for Management of Antiretroviral Therapy (SMART) Study Group

Background Despite declines in morbidity and mortality with the use of combination antiretroviral therapy, its effectiveness is limited by adverse events, problems with adherence, and resistance of the human immunodeficiency virus (HIV).

Methods We randomly assigned persons infected with HIV who had a CD4+ cell count of more than 350 per cubic millimeter to the continuous use of antiretroviral therapy (the viral suppression group) or the episodic use of antiretroviral therapy (the drug conservation group). Episodic use involved the deferral of therapy until the CD4+ count decreased to less than 250 per cubic millimeter and then the use of therapy until the CD4+ count increased to more than 350 per cubic millimeter. The primary end point was the development of an opportunistic disease or death from any cause. An important secondary end point was major cardiovascular, renal, or hepatic disease.

Results A total of 5472 participants (2720 assigned to drug conservation and 2752 to viral suppression) were followed for an average of 16 months before the protocol was modified for the drug conservation group. At baseline, the median and nadir CD4+ counts were 597 per cubic millimeter and 250 per cubic millimeter, respectively, and 71.7% of participants had plasma HIV RNA levels of 400 copies or less per milliliter. Opportunistic disease or death from any cause occurred in 120 participants (3.3 events per 100 person-years) in the drug conservation group and 47 participants (1.3 per 100 person-years) in the viral suppression group (hazard ratio for the drug conservation group vs. the viral suppression group, 2.6; 95% confidence interval [CI], 1.9 to 3.7; P<0.001). Hazard ratios for death from any cause and for major cardiovascular, renal, and hepatic disease were 1.8 (95% CI, 1.2 to 2.9; P=0.007) and 1.7 (95% CI, 1.1 to 2.5; P=0.009), respectively. Adjustment for the latest CD4+ count and HIV RNA level (as time-updated covariates) reduced the hazard ratio for the primary end point from 2.6 to 1.5 (95% CI, 1.0 to 2.1).

Conclusions Episodic antiretroviral therapy guided by the CD4+ count, as used in our study, significantly increased the risk of opportunistic disease or death from any cause, as compared with continuous antiretroviral therapy, largely as a consequence of lowering the CD4+ cell count and increasing the viral load. Episodic antiretroviral therapy does not reduce the risk of adverse events that have been associated with antiretroviral therapy.

abstract

http://content.nejm.org/cgi/content/abstract/355/22/2283

PDF

http://content.nejm.org/cgi/reprint/355/22/2283.pdf

 

November 30, 2009 at 12:40 pm Leave a comment

When to Start Antiretroviral Therapy?

Clinical  Infect Diseases  15 Dec  2008  V.47  N.12  p. 1580-6

Timothy J. Wilkin and Roy M. Gulick

Division of International Medicine and Infectious Diseases, Weill‐Cornell Medical College, New York, New York

The optimal time to start antiretroviral therapy (ART) for human immunodeficiency virus (HIV)–infected individuals remains uncertain. Although current ART regimens are effective in suppressing viremia and enhancing immune function and are increasingly convenient and well tolerated, ongoing concerns remain about adherence, drug-related toxicities, drug resistance, and cost. Although few clinical trials results are currently available to inform the question of when to start ART, large clinical cohorts clearly have demonstrated the benefits of earlier initiation of ART for reducing both HIV-related and non-HIV–related clinical events. Additional data suggest that the strategy of earlier initiation of ART is cost-effective and efficient. Consequently, many antiretroviral guidelines from around the world now recommend routine initiation of ART when the CD4 cell count decreases to <350 cells/μL or at higher CD4 cell counts for certain subgroups of HIV-infected individuals, such as pregnant and/or breast-feeding women and persons with HIV-related nephropathy or hepatitis virus coinfection. Additional cohort and clinical trials data are needed.

abstract

http://www.journals.uchicago.edu/doi/abs/10.1086/593311

PDF

http://www.journals.uchicago.edu/doi/pdf/10.1086/593311

November 30, 2009 at 12:39 pm Leave a comment

Serum procalcitonin and C-reactive protein levels as markers of bacterial infection: a systematic review and meta-analysis.

Clin Infect Dis. 15 July 2004  V.39  N.2  p.206-17

REVIEW ARTICLE

Liliana Simon,1 France Gauvin, 2 Devendra K. Amre,2 Patrick Saint‐Louis,3 and Jacques Lacroix2

1Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut; and Departments of 2Pediatrics and 3Clinical Biochemistry, University of Montreal, Quebec

A meta-analysis was performed to evaluate the accuracy of determination of procalcitonin (PCT) and C-reactive protein (CRP) levels for the diagnosis of bacterial infection. The analysis included published studies that evaluated these markers for the diagnosis of bacterial infections in hospitalized patients. PCT level was more sensitive (88% [95% confidence interval {CI}, 80%–93%] vs. 75% [95% CI, 62%–84%]) and more specific (81% [95% CI, 67%–90%] vs. 67% [95% CI, 56%–77%]) than CRP level for differentiating bacterial from noninfective causes of inflammation. The Q value for PCT markers was higher (0.82 vs. 0.73). The sensitivity for differentiating bacterial from viral infections was also higher for PCT markers (92% [95% CI, 86%–95%] vs. 86% [95% CI, 65%–95%]); the specificities were comparable (73% [95% CI, 42%–91%] vs. 70% [95% CI, 19%–96%]). The Q value was higher for PCT markers (0.89 vs. 0.83). PCT markers also had a higher positive likelihood ratio and lower negative likelihood ratio than did CRP markers in both groups. On the basis of this analysis, the diagnostic accuracy of PCT markers was higher than that of CRP markers among patients hospitalized for suspected bacterial infections.

abstract

http://www.journals.uchicago.edu/doi/abs/10.1086/421997

PDF

http://www.journals.uchicago.edu/doi/pdf/10.1086/421997

ERRATUM

http://www.journals.uchicago.edu/doi/full/10.1086/429520

PDF

http://www.journals.uchicago.edu/doi/pdf/10.1086/429520

November 28, 2009 at 5:38 pm Leave a comment

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