The effect of antiretroviral treatment of different durations in primary HIV infection.

OBJECTIVES: To compare immunological, virological and clinical outcomes in persons initiating combination antiretroviral therapy (cART of different durations within 6 months of seroconversion (early treated) with those who deferred therapy (deferred group). DESIGN: CD4 cell and HIV-RNA measurements for 'early treated' individuals following treatment cessation were compared with the corresponding ART-free period for the 'deferred' group using piecewise linear mixed models. Individuals identified during primary HIV infection were included if they seroconverted from 1st January 1996 and were at least 15 years of age at seroconversion. Those with at least 2 CD4 less than 350 cells/microl or AIDS within the first 6 months following seroconversion were excluded. RESULTS: Of 348 'early treated' patients, 147 stopped cART following treatment for at least 6 (n = 38), more than 6-12 (n = 40) or more than 12 months (n = 69). CD4 cell loss was steeper for the first 6 months following cART cessation, but subsequent loss rate was similar to the 'deferred' group (n = 675, P = 0.26). Although those treated for more than 12 months appeared to maintain higher CD4 cell counts following cART cessation, those treated for 12 months or less had CD4 cell counts 6 months after cessation comparable to those in the 'deferred' group. There was no difference in HIV-RNA set points between the 'early' and 'deferred' groups (P = 0.57). AIDS rates were similar but death rates, mainly due to non-AIDS causes, were higher in the 'deferred' group (P = 0.05). CONCLUSION: Transient cART, initiated within 6 months of seroconversion, seems to have no effect on viral load set point and limited beneficial effect on CD4 cell levels in individuals treated for more than 12 months. Its long-term effects remain inconclusive and need further investigation.

Human cytomegalovirus glycoprotein UL141 targets the TRAIL death receptors to thwart host innate antiviral defenses.

Death receptors (DRs) of the TNFR superfamily contribute to antiviral immunity by promoting apoptosis and regulating immune homeostasis during infection, and viral inhibition of DR signaling can alter immune defenses. Here we identify the human cytomegalovirus (HCMV) UL141 glycoprotein as necessary and sufficient to restrict TRAIL DR function. Despite showing no primary sequence homology to TNF family cytokines, UL141 binds the ectodomains of both human TRAIL DRs with affinities comparable to the natural ligand TRAIL. UL141 binding promotes intracellular retention of the DRs, thus protecting virus infected cells from TRAIL and TRAIL-dependent NK cell-mediated killing. The identification of UL141 as a herpesvirus modulator of the TRAIL DRs strongly implicates this pathway as a regulator of host defense to HCMV and highlights UL141 as a pleiotropic inhibitor of NK cell effector function.

Johnston, Special Investigation Public Works Department, July 1, 1999 - February 17, 2003

City Audit Report, Special Investigation

Report on Special Investigation of the City of Van Horne, June 01, 2000 - December 31, 2002

City Audit Report, Special Investigation

Special Investigation of the Hardin County Recorder's Office, July 1, 2000 - April 28, 2003

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Special Investigation of the Johnson County Mental Health/Developmental Disabilities Department, June 30, 2002

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Report on Special Investigation of the Webster County Sheriff's Office, July 1, 1997 - February 28, 2003

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Fourth Judicial District Department of Correctional Services - Special Investigation, September 1, 2000 - March 7, 2002

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Report on Special Investigation of the City of Preston Library, June 14, 1999 - August 25, 2003

City Audit Report - Special Investigation

Special Investigation Anita Municipal Utilities, Anita Iowa, December 30, 2003

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Report on the Special Investigation of the Nutrition Department of the Boone Community School District, For the Period August 30, 2004 through March 31, 2006 and Selected Activity for the period February 28, 2000 through March 31, 2006

Community School District Audit Report - Special Investigation

Report on Special Investigation of the Parkersburg Economic Development Corporation in Parkersburg Iowa, May 1, 1999 - October 16, 2003

City Audit Report

Report on Special Investigation of the Taylor County Sanitarian's Office, July 29, 2002 through December 31, 2003

County Audit Report - Special Investigation