Archive for August 6, 2008

The President’s Emergency Plan for AIDS Relief — Is the Emergency Over?

N Engl J of Medicine  August 7, 2008  V.359  N.6  p.553-555

Perspective

Wafaa M. El-Sadr, M.D., M.P.H., and David Hoos, M.D., M.P.H.

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August 6, 2008 at 11:27 pm Leave a comment

Malaria Prevention in Short-Term Travelers

N Engl J of Medicine  August 7, 2008  V.359  N.6  p.603-612

Clinical Practice

David O. Freedman, M.D.

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August 6, 2008 at 11:25 pm Leave a comment

Comprehensive Treatment of Extensively Drug-Resistant Tuberculosis

N Engl J of Medicine  August 7, 2008  V.359  N.6  p.563-574

Carole D. Mitnick, Sc.D., Sonya S. Shin, M.D., Kwonjune J. Seung, M.D., Michael L. Rich, M.D., Sidney S. Atwood, B.A., Jennifer J. Furin, M.D., Ph.D., Garrett M. Fitzmaurice, Sc.D., Felix A. Alcantara Viru, M.D., Sasha C. Appleton, Sc.M., Jaime N. Bayona, M.D., Cesar A. Bonilla, M.D., Katiuska Chalco, R.N., Sharon Choi, M.S., Molly F. Franke, B.A., Hamish S.F. Fraser, M.B., Ch.B., Dalia Guerra, Rocio M. Hurtado, M.D., Darius Jazayeri, M.S., Keith Joseph, M.D., Karim Llaro, R.N., Lorena Mestanza, R.N., Joia S. Mukherjee, M.D., Maribel Muñoz, R.N., Eda Palacios, R.N., Epifanio Sanchez, M.D., Alexander Sloutsky, Ph.D., and Mercedes C. Becerra, Sc.D.

ABSTRACT

Background Extensively drug-resistant tuberculosis has been reported in 45 countries, including countries with limited resources and a high burden of tuberculosis. We describe the management of extensively drug-resistant tuberculosis and treatment outcomes among patients who were referred for individualized outpatient therapy in Peru.

Methods A total of 810 patients were referred for free individualized therapy, including drug treatment, resective surgery, adverse-event management, and nutritional and psychosocial support. We tested isolates from 651 patients for extensively drug-resistant tuberculosis and developed regimens that included five or more drugs to which the infecting isolate was not resistant.

Results Of the 651 patients tested, 48 (7.4%) had extensively drug-resistant tuberculosis; the remaining 603 patients had multidrug-resistant tuberculosis. The patients with extensively drug-resistant tuberculosis had undergone more treatment than the other patients (mean [±SD] number of regimens, 4.2±1.9 vs. 3.2±1.6; P<0.001) and had isolates that were resistant to more drugs (number of drugs, 8.4±1.1 vs. 5.3±1.5; P<0.001). None of the patients with extensively drug-resistant tuberculosis were coinfected with the human immunodeficiency virus (HIV). Patients with extensively drug-resistant tuberculosis received daily, supervised therapy with an average of 5.3±1.3 drugs, including cycloserine, an injectable drug, and a fluoroquinolone. Twenty-nine of these patients (60.4%) completed treatment or were cured, as compared with 400 patients (66.3%) with multidrug-resistant tuberculosis (P=0.36).

Conclusions Extensively drug-resistant tuberculosis can be cured in HIV-negative patients through outpatient treatment, even in those who have received multiple prior courses of therapy for tuberculosis.

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Editorial
Facing Extensively Drug-Resistant Tuberculosis — A Hope and a Challenge

Mario C. Raviglione, M.D.

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August 6, 2008 at 11:23 pm Leave a comment

Antiretroviral Treatment of Adult HIV Infection – 2008 Recommendations of the International AIDS Society–USA Panel

JAMA  6 August 2008  V.300  N.5  p.555-570

HIV/AIDS

Scott M. Hammer, MD; Joseph J. Eron Jr, MD; Peter Reiss, MD, PhD; Robert T. Schooley, MD; Melanie A. Thompson, MD; Sharon Walmsley, MD; Pedro Cahn, MD; Margaret A. Fischl, MD; Jose M. Gatell, MD, PhD; Martin S. Hirsch, MD; Donna M. Jacobsen, BS; Julio S. G. Montaner, MD; Douglas D. Richman, MD; Patrick G. Yeni, MD; Paul A. Volberding, MD

Columbia University College of Physicians and Surgeons, New York, New York (Dr Hammer); University of North Carolina at Chapel Hill (Dr Eron); Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands (Dr Reiss); University of California San Diego, La Jolla (Dr Schooley); AIDS Research Consortium of Atlanta, Atlanta, Georgia (Dr Thompson); University of Toronto, Toronto, Ontario, Canada (Dr Walmsley); Hospital Juan Fernandez/University of Buenos Aires Medical School and Fundacion Huesped, Buenos Aires, Argentina (Dr Cahn); University of Miami, Miami, Florida (Dr Fischl); University of Barcelona, Barcelona, Spain (Dr Gatell); Harvard Medical School, Boston, Massachusetts (Dr Hirsch); International AIDS Society–USA (Ms Jacobsen) and University of California San Francisco and San Francisco Veterans Affairs Medical Center (Dr Volberding), San Francisco; University of British Columbia, Vancouver, British Columbia, Canada (Dr Montaner); University of California San Diego and Veterans Affairs San Diego Healthcare System, San Diego (Dr Richman); and Hôpital Bichat-Claude Bernard and Xavier Bichat Medical School, Paris, France (Dr Yeni).

Context  The availability of new antiretroviral drugs and formulations, including drugs in new classes, and recent data on treatment choices for antiretroviral-naive and -experienced patients warrant an update of the International AIDS Society–USA guidelines for the use of antiretroviral therapy in adult human immunodeficiency virus (HIV) infection.

Objectives  To summarize new data in the field and to provide current recommendations for the antiretroviral management and laboratory monitoring of HIV infection. This report provides guidelines in key areas of antiretroviral management: when to initiate therapy, choice of initial regimens, patient monitoring, when to change therapy, and how best to approach treatment options, including optimal use of recently approved drugs (maraviroc, raltegravir, and etravirine) in treatment-experienced patients.

Data Sources and Study Selection  A 14-member panel with expertise in HIV research and clinical care was appointed. Data published or presented at selected scientific conferences since the last panel report (August 2006) through June 2008 were identified.

Data Extraction and Synthesis  Data that changed the previous guidelines were reviewed by the panel (according to section). Guidelines were drafted by section writing committees and were then reviewed and edited by the entire panel. Recommendations were made by panel consensus.

Conclusions  New data and considerations support initiating therapy before CD4 cell count declines to less than 350/µL. In patients with 350 CD4 cells/µL or more, the decision to begin therapy should be individualized based on the presence of comorbidities, risk factors for progression to AIDS and non-AIDS diseases, and patient readiness for treatment. In addition to the prior recommendation that a high plasma viral load (eg, >100 000 copies/mL) and rapidly declining CD4 cell count (>100/µL per year) should prompt treatment initiation, active hepatitis B or C virus coinfection, cardiovascular disease risk, and HIV-associated nephropathy increasingly prompt earlier therapy. The initial regimen must be individualized, particularly in the presence of comorbid conditions, but usually will include efavirenz or a ritonavir-boosted protease inhibitor plus 2 nucleoside reverse transcriptase inhibitors (tenofovir/emtricitabine or abacavir/lamivudine). Treatment failure should be identified and managed promptly, with the goal of therapy, even in heavily pretreated patients, being an HIV-1 RNA level below assay detection limits.

abstract 
http://jama.ama-assn.org/cgi/content/abstract/300/5/555?etoc

August 6, 2008 at 5:42 pm Leave a comment

Highly Active Antiretroviral Therapy and Survival in HIV-Infected Injection Drug Users

JAMA  6 August 2008  V.300  N.5  p.550-554

HIV/AIDS

Evan Wood, MD, PhD; Robert S. Hogg, PhD; Viviane Dias Lima, PhD; Thomas Kerr, PhD; Benita Yip, BSc (Pharm); Brandon D. L. Marshall, MSc; Julio S. G. Montaner, MD, FRCPC

British Columbia Centre for Excellence in HIV/AIDS, St Paul’s Hospital, Vancouver; Faculty of Medicine, University of British Columbia, Vancouver (Drs Wood, Lima, Kerr, and Montaner); and Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia (Dr Hogg).

Context  Highly active antiretroviral therapy (HAART) is often withheld from injection drug users (IDUs) infected with the human immunodeficiency virus (HIV) based on the belief that their unstable lifestyles may predetermine a markedly inferior outcome with HAART. However, long-term evaluations of HIV treatment outcomes among IDUs in comparison with other risk groups are not available.

Objective  To compare survival rates among HIV-infected patients initiating HAART with and without a history of injection drug use.

Design, Setting, and Patients  Population-based, prospective cohort study (HAART Observational Medical Evaluation and Research [HOMER]) of 3116 antiretroviral-naive HIV-infected patients in a province-wide HIV/AIDS treatment program in British Columbia, Canada. Of the 3116 patients, 915 were IDUs (29.4%), 579 were female (18.6%), and the median age was 39.4 years (interquartile range, 33.3-46.4 years). Treatment with HAART was initiated between August 1, 1996, and June 30, 2006. The median duration of follow-up was 5.3 years (interquartile range, 2.8-8.3 years) for IDUs and 4.3 years (interquartile range, 2.0-7.6 years) for non-IDUs. Patients were followed up until June 30, 2007. Data were analyzed between November 1, 2007, and May 26, 2008.

Main Outcome Measure  All-cause mortality.

Results  Overall, 622 individuals died (20.0%) during the study period (232 IDUs and 390 non-IDUs), for a crude mortality rate of 20.0% (95% confidence interval [CI], 18.4%-21.5%). At 84 months after the initiation of HAART, the product limit estimate of the cumulative all-cause mortality rate was similar between the 915 IDUs (26.5%; 95% CI, 23.2%-29.8%) and 2201 non-IDUs (21.6%; 95% CI, 16.9%-26.2%) (Wilcoxon P = .47). In multivariate time-updated Cox regression, the hazard ratio of mortality was similar between IDUs and non-IDUs (1.09; 95% CI, 0.92-1.29).

Conclusion  In this study population, injection drug use was not associated with decreased survival among HIV-infected patients initiating HAART.

abstract 
http://jama.ama-assn.org/cgi/content/abstract/300/5/550?etoc

August 6, 2008 at 5:39 pm Leave a comment

Outcomes of Nevirapine- and Efavirenz-Based Antiretroviral Therapy When Coadministered With Rifampicin-Based Antitubercular Therapy

JAMA  6 August 2008  V.300  N.5  p.530-539

HIV/AIDS

Andrew Boulle, MBChB, MSc; Gilles Van Cutsem, MD, MPH; Karen Cohen, MBChB, MSc; Katherine Hilderbrand, MSc; Shaheed Mathee, MBChB, BSc; Musaed Abrahams, MBChB; Eric Goemaere, MD, DSc; David Coetzee, MBBCh, MSc; Gary Maartens, MBChB, MMed

School of Public Health and Family Medicine (Drs Boulle and Coetzee and Ms Hilderbrand), Division of Clinical Pharmacology, Department of Medicine (Drs Cohen and Maartens), University of Cape Town, Médecins Sans Frontières (Drs Van Cutsem and Goemaere and Ms Hilderbrand), and Site B Community Health Centre, Department of Health, Provincial Government of the Western Cape (Drs Mathee and Abrahams), Cape Town, South Africa.

Context  Rifampicin-based antitubercular therapy reduces the plasma concentrations of nevirapine and efavirenz. The virological consequences of these interactions are not well described.

Objective  To assess the effectiveness and tolerability of concomitant efavirenz- or nevirapine-based combination antiretroviral therapy and rifampicin-based antitubercular therapy.

Design, Setting, and Participants  Cohort analysis of prospectively collected routine clinical data in a community–based South African antiretroviral treatment program. Antiretroviral treatment-naive adults enrolled between May 2001 and June 2006 were included in the analysis, and were followed up until the end of 2006.

Interventions  Patients starting antiretroviral therapy with or without concurrent antitubercular therapy received either efavirenz or nevirapine at standard doses. Patients developing tuberculosis while taking antiretroviral therapy that included nevirapine were either changed to efavirenz or continued taking nevirapine.

Main Outcome Measures  Viral load of 400 copies/mL or more after 6, 12, and 18 months of antiretroviral therapy; time to the first viral load of 400 copies/mL or more; time to confirmed virological failure (2 consecutive values 5000 copies/mL); time to death; and time to treatment-limiting toxicity were assessed.

Results  The analysis included 2035 individuals who started antiretroviral therapy with efavirenz (1074 with concurrent tuberculosis) and 1935 with nevirapine (209 with concurrent tuberculosis). There were no differences in time to death or substitution of either antiretroviral drug for toxicity with and without concurrent tuberculosis. Patients starting nevirapine with concurrent tuberculosis were at a higher risk of elevated viral load most notably at 6 months (16.3%; 95% confidence interval [CI], 10.6%-23.5%) than those without tuberculosis (8.3%; 95% CI, 6.7%-10.0%; adjusted odds ratio [OR], 2.1; 95% CI, 1.2-3.4; and in the combined estimate, adjusted OR, 1.7; 95% CI, 1.2-2.6). In the time-to-event analysis of confirmed virological failure (2 consecutive values of 5000 copies/mL), patients starting nevirapine with concurrent tuberculosis developed virological failure sooner (adjusted hazard ratio [HR] 2.2; 95% CI, 1.3-3.7). There were no differences between patients starting efavirenz with and without concurrent tuberculosis (adjusted OR, 1.1; 95% CI, 0.8-1.5 [combined estimate] and adjusted HR, 1.1; 95% CI, 0.6-2.0, respectively). There was no difference in time to virological rebound in patients free of tuberculosis and those developing tuberculosis during follow-up while taking nevirapine (adjusted HR, 1.0; 95% CI, 0.5-2.0) or efavirenz (adjusted HR, 0.8; 95% CI, 0.4-1.7).

Conclusion  In this cohort study, virological outcomes were inferior when nevirapine-based antiretroviral therapy was commenced while taking antitubercular treatment (vs without concurrent tuberculosis) but comparable when starting efavirenz-based antiretroviral therapy (vs without concurrent tuberculosis) or when tuberculosis developed while taking established nevirapine- or efavirenz-based therapies.

abstract 
http://jama.ama-assn.org/cgi/content/abstract/300/5/530?etoc

August 6, 2008 at 5:36 pm Leave a comment

Estimation of HIV Incidence in the United States

JAMA  6 August 2008  V.300  N.5  p.520-529

HIV/AIDS

H. Irene Hall, PhD; Ruiguang Song, PhD; Philip Rhodes, PhD; Joseph Prejean, PhD; Qian An, MS; Lisa M. Lee, PhD; John Karon, PhD; Ron Brookmeyer, PhD; Edward H. Kaplan, PhD; Matthew T. McKenna, MD; Robert S. Janssen, MD; for the HIV Incidence Surveillance Group

 Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia (Drs Hall, Song, Rhodes, Prejean, Lee, McKenna, and Janssen); The Ginn Group Inc, Peachtree City, Georgia (Ms An); Emergint Corporation, Louisville, Kentucky (Dr Karon); Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland (Dr Brookmeyer); and Yale School of Management, Department of Epidemiology and Public Health, Yale School of Medicine, and Yale School of Engineering and Applied Science, New Haven, Connecticut (Dr Kaplan). Dr Janssen is now with Gilead Sciences Inc, Foster City, California.

Context  Incidence of human immunodeficiency virus (HIV) in the United States has not been directly measured. New assays that differentiate recent vs long-standing HIV infections allow improved estimation of HIV incidence.

Objective  To estimate HIV incidence in the United States.

Design, Setting, and Patients  Remnant diagnostic serum specimens from patients 13 years or older and newly diagnosed with HIV during 2006 in 22 states were tested with the BED HIV-1 capture enzyme immunoassay to classify infections as recent or long-standing. Information on HIV cases was reported to the Centers for Disease Control and Prevention through June 2007. Incidence of HIV in the 22 states during 2006 was estimated using a statistical approach with adjustment for testing frequency and extrapolated to the United States. Results were corroborated with back-calculation of HIV incidence for 1977-2006 based on HIV diagnoses from 40 states and AIDS incidence from 50 states and the District of Columbia.

Main Outcome Measure  Estimated HIV incidence.

Results  An estimated 39 400 persons were diagnosed with HIV in 2006 in the 22 states. Of 6864 diagnostic specimens tested using the BED assay, 2133 (31%) were classified as recent infections. Based on extrapolations from these data, the estimated number of new infections for the United States in 2006 was 56 300 (95% confidence interval [CI], 48 200-64 500); the estimated incidence rate was 22.8 per 100 000 population (95% CI, 19.5-26.1). Forty-five percent of infections were among black individuals and 53% among men who have sex with men. The back-calculation (n = 1.230 million HIV/AIDS cases reported by the end of 2006) yielded an estimate of 55 400 (95% CI, 50 000-60 800) new infections per year for 2003-2006 and indicated that HIV incidence increased in the mid-1990s, then slightly declined after 1999 and has been stable thereafter.

Conclusions  This study provides the first direct estimates of HIV incidence in the United States using laboratory technologies previously implemented only in clinic-based settings. New HIV infections in the United States remain concentrated among men who have sex with men and among black individuals.

abstract 
http://jama.ama-assn.org/cgi/content/abstract/300/5/520?etoc

August 6, 2008 at 5:34 pm Leave a comment

Low-Dose Physiological Growth Hormone in Patients With HIV and Abdominal Fat Accumulation

JAMA  6 August 2008  V.300  N.5  p.509-519

HIV/AIDS

Janet Lo, MD, MMSc; Sung Min You, BA; Bridget Canavan, MD; James Liebau, ANP; Greg Beltrani, BA; Polyxeni Koutkia, MD; Linda Hemphill, MD; Hang Lee, PhD; Steven Grinspoon, MD

Program in Nutritional Metabolism and Neuroendocrine Unit (Drs Lo, Canavan, Koutkia, and Grinspoon, and Ms You, and Messrs Liebau and Beltrani), Boston Heart Foundation (Dr Hemphill), and Department of Biostatistics (Dr Lee), Massachusetts General Hospital, Boston.

Context  Antiretroviral therapy can be associated with visceral adiposity and metabolic complications, increasing cardiovascular risk, and reduced growth hormone (GH) secretion may be a contributing factor.

Objective  To investigate the effects of low-dose physiological GH administration on body composition, glucose, and cardiovascular parameters in patients with human immunodeficiency virus (HIV) having abdominal fat accumulation and relative GH deficiency.

Design, Setting, and Patients  A randomized, double-blind, placebo-controlled trial of 56 patients with HIV, abdominal fat accumulation, and reduced GH secretion (peak GH <7.5 ng/mL) conducted at a US academic medical center between November 2003 and October 2007.

Intervention  Patients were randomly assigned to receive either subcutaneous GH or matching placebo titrated to the upper quartile of normal insulinlike growth factor 1 (IGF-1) range for 18 months. Starting dose was 2 µg/kg/d and increased to maximum dose of 6 µg/kg/d (average dose, 0.33 mg/d).

Main Outcome Measures  Change in body composition assessed by computed tomographic scan and dual-energy x-ray absorptiometry. Secondary outcomes included glucose, IGF-1, blood pressure (BP), and lipids. Treatment effect was the difference in the change between GH and placebo groups, using all available data.

Results  Fifty-five patients (26 with GH and 29 with placebo) were included in the safety analyses and 52 patients (25 with GH and 27 with placebo) were included in the efficacy analyses. Visceral adipose tissue area (treatment effect [last-value-carried-forward analysis {n = 56}, –19 cm2; 95% confidence interval {CI}, –37 to –0.3 cm2], –19 cm2; 95% CI, –38 to –0.5 cm2; P = .049); trunk fat (–0.8 kg; 95% CI, –1.5 to –0.04 kg; P = .04); diastolic BP (–7 mm Hg; 95% CI, –11 to –2 mm Hg; P = .006); and triglycerides (–7 mg/dL, P = .002) improved but 2-hour glucose levels on glucose tolerance testing increased in the GH group vs the placebo group (treatment effect, 22 mg/dL; 95% CI, 6-37 mg/dL; P = .009). The IGF-1 levels increased (treatment effect, 129 ng/mL; 95% CI, 95-164 ng/mL; P < .001). Adverse events were not increased for GH vs placebo (23%; 95% CI, 9%-44% vs 28%; 95% CI, 13%-47%; P = .70).

Conclusions  In HIV-associated abdominal fat accumulation and relative GH deficiency, low-dose GH received for 18 months resulted in significantly reduced visceral fat and truncal obesity, triglycerides, and diastolic BP, but 2-hour glucose levels on glucose tolerance testing were increased.

abstract 
http://jama.ama-assn.org/cgi/content/abstract/300/5/509?etoc

August 6, 2008 at 5:32 pm Leave a comment


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