Archive for April 14, 2009

Effect of Early versus Deferred Antiretroviral Therapy for HIV on Survival

N Engl J of Medicine April 2, 2009 V.360 N.14

Mari M. Kitahata, M.D., M.P.H., Stephen J. Gange, Ph.D., Alison G. Abraham, Ph.D., Barry Merriman, M.A., Michael S. Saag, M.D., Amy C. Justice, M.D., Ph.D., Robert S. Hogg, Ph.D., Steven G. Deeks, M.D., Joseph J. Eron, M.D., John T. Brooks, M.D., Sean B. Rourke, Ph.D., M. John Gill, M.B., Ch.B., Ronald J. Bosch, Ph.D., Jeffrey N. Martin, M.D., M.P.H., Marina B. Klein, M.D., Lisa P. Jacobson, Sc.D., Benigno Rodriguez, M.D., Timothy R. Sterling, M.D., Gregory D. Kirk, M.D., Ph.D., Sonia Napravnik, Ph.D., Anita R. Rachlis, M.D., Liviana M. Calzavara, Ph.D., Michael A. Horberg, M.D., Michael J. Silverberg, Ph.D., Kelly A. Gebo, M.D., M.P.H., James J. Goedert, M.D., Constance A. Benson, M.D., Ann C. Collier, M.D., Stephen E. Van Rompaey, Ph.D., Heidi M. Crane, M.D., M.P.H., Rosemary G. McKaig, Ph.D., Bryan Lau, Ph.D., Aimee M. Freeman, M.A., Richard D. Moore, M.D., for the NA-ACCORD Investigators

Background The optimal time for the initiation of antiretroviral therapy for asymptomatic patients with human immunodeficiency virus (HIV) infection is uncertain.

Methods We conducted two parallel analyses involving a total of 17,517 asymptomatic patients with HIV infection in the United States and Canada who received medical care during the period from 1996 through 2005. None of the patients had undergone previous antiretroviral therapy. In each group, we stratified the patients according to the CD4+ count (351 to 500 cells per cubic millimeter or >500 cells per cubic millimeter) at the initiation of antiretroviral therapy. In each group, we compared the relative risk of death for patients who initiated therapy when the CD4+ count was above each of the two thresholds of interest (early-therapy group) with that of patients who deferred therapy until the CD4+ count fell below these thresholds (deferred-therapy group).

Results In the first analysis, which involved 8362 patients, 2084 (25%) initiated therapy at a CD4+ count of 351 to 500 cells per cubic millimeter, and 6278 (75%) deferred therapy. After adjustment for calendar year, cohort of patients, and demographic and clinical characteristics, among patients in the deferred-therapy group there was an increase in the risk of death of 69%, as compared with that in the early-therapy group (relative risk in the deferred-therapy group, 1.69; 95% confidence interval [CI], 1.26 to 2.26; P<0.001). In the second analysis involving 9155 patients, 2220 (24%) initiated therapy at a CD4+ count of more than 500 cells per cubic millimeter and 6935 (76%) deferred therapy. Among patients in the deferred-therapy group, there was an increase in the risk of death of 94% (relative risk, 1.94; 95% CI, 1.37 to 2.79; P<0.001).

Conclusions The early initiation of antiretroviral therapy before the CD4+ count fell below two prespecified thresholds significantly improved survival, as compared with deferred therapy.

abstract

http://content.nejm.org/cgi/content/full/NEJMoa0807252?query=TOC

PDF

http://content.nejm.org/cgi/reprint/NEJMoa0807252v1.pdf

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April 14, 2009 at 11:31 pm Leave a comment

Rapidly Cleared Episodes of Herpes Simplex Virus Reactivation in Immunocompetent Adults

Journal of Infectious Diseases  15 October 2008  V.198, N.8  p.1141–1149
Karen E. Mark,1,4 Anna Wald,1,2,3,4 Amalia S. Magaret,3,4 Stacy Selke,3 Laura Olin,3 Meei-Li Huang,3 and
Lawrence Corey1,3,4
Departments of 1Medicine, 2Epidemiology, and 3Laboratory Medicine, University of Washington, and 4Vaccine and Infectious Diseases Institute, Fred Hutchinson Cancer Research Center, Seattle, Washington
Background.Herpes simplex virus (HSV) remains latent in nerve root ganglia of infected persons and is thought to reactivate several times yearly. Recent in situ data show the localization of HSV-specific CD8+ T cells at the dermal epidermal junction next to peripheral sensory nerve endings, suggesting that viral reactivation may occur more frequently than previously appreciated.
Methods.Twenty-five HSV-2–seropositive and 18 HSV-1–seropositive healthy adults collected anogenital and oral swabs, respectively, 4 times per day for 60 days. Swabs were assayed for HSV, using a quantitative polymerase chain reaction assay.
Results.Twenty-four percent of anogenital reactivations and 21% of oral reactivations lasted 6 h, and 49% of anogenital reactivations and 39% of oral reactivations lasted 12 h. Lesions were reported in only 3 (7%) of 44 anogenital reactivations and 1 (8%) of 13 oral reactivations lasting 12 h. The median HSV DNA levels at initial and last detection were 103.5 and 103.3 copies/mL, respectively, during anogenital reactivation and 103.7 and 103.0 copies/mL, respectively, during oral reactivation.
Conclusions.This high frequency of short subclinical HSV reactivation in immunocompetent hosts strongly suggests that the peripheral mucosal immune system plays a critical role in clearing HSV reactivations.
abstract
http://www.journals.uchicago.edu/doi/abs/10.1086/591913
PDF
http://www.journals.uchicago.edu/doi/pdf/10.1086/591913

April 14, 2009 at 5:44 pm Leave a comment

Emergence and Persistence of CXCR4-Tropic HIV-1 in a Population of Men from the Multicenter AIDS Cohort Study

Journal of Infectious Diseases  15 October 2008  V.198, N.8  p.1104–1112
James C. Shepherd,1,3 Lisa P. Jacobson,2 Wei Qiao,2 Beth D. Jamieson,5 John P. Phair,6,7 Paolo Piazza,8 Thomas C. Quinn,1,4 and Joseph B. Margolick2
1School of Medicine and 2Bloomberg School of Public Health, Johns Hopkins University, and 3School of Medicine, University of Maryland, Baltimore, and 4National Institute of Allergy and Infectious Diseases, Bethesda, Maryland; 5David Geffen School of Medicine, University of California, Los Angeles; 6Howard Brown Health Center and 7Feinberg School of Medicine, Northwestern University, Chicago, Illinois; and 8Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania
We examined the emergence of CXCR4 (i.e., X4) tropism in 67 male human immunodeficiency virus type 1 (HIV-1) seroconverters from the Multicenter AIDS Cohort Study (MACS) who were selected to reflect the full spectrum of rates of HIV-1 disease progression. A mean of 10 serial samples per donor were evaluated by a laboratory-validated, commercially available assay to determine phenotypic coreceptor use. A total of 52% of men had dual- or mixed-tropic HIV-1 detected at 1 or more of the time points tested. Use of X4 by HIV-1 was detected more frequently among men who developed AIDS (defined as a CD4+ T cell count of <200 cells/μL and/or an AIDS-defining illness) 11 years after seroconversion than among those who did not ( ), as well as among men who exhibited a total T cell count decline (i.e., a CD3+ inflection point), compared with those who did not ( ). For men in whom both X4 virus and an inflection point were detected, emergence of X4 virus preceded the inflection point by a median of 0.83 years. The median CD4+ T cell count at first detection of X4 viruses before the onset of AIDS was 475 cells/μL. We conclude that HIV-1 variants that used X4 frequently emerged at high CD4+ T cell counts and may contribute to the decrease in T cell numbers during late HIV-1 infection.
abstract
http://www.journals.uchicago.edu/doi/abs/10.1086/591623
PDF
http://www.journals.uchicago.edu/doi/pdf/10.1086/591623
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Journal of Infectious Diseases  15 October 2008  V.198, N.8  p.1095–1097
EDITORIAL COMMENTARY
HIV-1 Tropism, Disease Progression, and Clinical Management
Harold Burger1,2,3 and Donald Hoover4
1Wadsworth Center, New York State Department of Health, and Divisions of 2HIV Medicine and 3Infectious Diseases, Albany Medical College, Albany, New York; and 4Department of Statistics, Rutgers University, Piscataway, New Jersey
Full Text
http://www.journals.uchicago.edu/doi/full/10.1086/591624
PDF
http://www.journals.uchicago.edu/doi/pdf/10.1086/591624
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April 14, 2009 at 5:43 pm Leave a comment


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