Characterization of Acute and Recent HIV-1 Infections in Zurich: a Long-Term Observational Study - Full Text View

Sponsor:	University of Zurich
Information provided by:	University of Zurich
ClinicalTrials.gov Identifier:	NCT00537966

Purpose

Aim of the study: To describe the epidemiology, longitudinally follow, test the effect of early antiretroviral treatment and investigate early events of virus-host interactions in patients with documented acute or recent HIV-1 infection in Zurich.

Study design: This is an open label, non-randomized, observational, single center study at the University Hospital Zurich, Division of Infectious Diseases and Hospital Epidemiology. We aim at enrolling approximately 300 patients over a 10 year period. All patients who fulfill the inclusion criteria of a documented acute or recent HIV infection can participate in the study. Patients are offered early combination antiretroviral treatment (cART), if treatment start falls within 90 days after diagnosis of acute HIV-infection. After one year of suppressed HIV-plasma viremia (< 50 copies/ml) patients can chose to stop cART. Patients who have not chosen to undergo early-cART, respectively will stop cART after one year will be followed for a total of 5 years. Viral setpoints reached after treatment interruptions will be compared to historic controls and to the control group not having received cART during acute infection. A battery of virological and immunological assays will be performed on blood samples obtained to better understand early virus-host interactions, which are thought to play a key role in HIV-pathogenesis research.

Summary: In summary, this study will provide comprehensive knowledge on early HIV-infection with regard to epidemiology, impact of early-cART on the course of disease and forms the base for a variety of translational research projects addressing early key pathogenesis events between virus and host, relevant for the course of disease, for transmission, for development of vaccines and new treatment strategies.

Trial with medicinal product

Condition	Intervention
HIV Infections	Drug: lopinavir Drug: atazanavir Drug: efavirenz Drug: fosamprenavir Drug: darunavir Drug: tipranavir Drug: ritonavir Drug: nevirapine Drug: zidovudine Drug: lamivudine Drug: tenofovir Drug: emtricitabine Drug: abacavir

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Parallel Assignment, Efficacy Study
Official Title:	Characterization of Acute and Recent HIV-1 Infections in Zurich: a Long-Term Observational Study

Resource links provided by NLM:

Further study details as provided by University of Zurich:

Primary Outcome Measures:

To evaluate the effect of early-cART on the viral setpoint [ Time Frame: 2016 ] [ Designated as safety issue: No ]

Estimated Enrollment:	2016
Study Start Date:	January 2002
Estimated Study Completion Date:	December 2016
Estimated Primary Completion Date:	December 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Control: No Intervention Patients with primary HIV-1 infection who do not want to undergo early combination antiretroviral treatment
Intervention: Active Comparator In this arm patients with primary HIV-1 infection will receive early combination antiretroviral therapy with standard drugs approved by Swiss Medic.	Drug: lopinavir In this arm patients with primary HIV-1 infection are treated with standard antiretroviral combination therapy (only drugs that have been approved by Swiss Medic) Drug: atazanavir standard dosage Drug: efavirenz standard dosage Drug: fosamprenavir standard dosage Drug: darunavir standard dosage Drug: tipranavir standard dosage Drug: ritonavir used only as booster for the protease inhibitors that are prescribed in this study according to standard boosting Drug: nevirapine standard dosage Drug: zidovudine standard dosage Drug: lamivudine standard dosage Drug: tenofovir standard dosage Drug: emtricitabine standard dosage Drug: abacavir standard dosage

Arms

Assigned Interventions

Control: No Intervention

Patients with primary HIV-1 infection who do not want to undergo early combination antiretroviral treatment

Intervention: Active Comparator

In this arm patients with primary HIV-1 infection will receive early combination antiretroviral therapy with standard drugs approved by Swiss Medic.

Drug: lopinavir

In this arm patients with primary HIV-1 infection are treated with standard antiretroviral combination therapy (only drugs that have been approved by Swiss Medic)

Drug: atazanavir

standard dosage

Drug: efavirenz

standard dosage

Drug: fosamprenavir

standard dosage

Drug: darunavir

standard dosage

Drug: tipranavir

standard dosage

Drug: ritonavir

used only as booster for the protease inhibitors that are prescribed in this study according to standard boosting

Drug: nevirapine

standard dosage

Drug: zidovudine

standard dosage

Drug: lamivudine

standard dosage

Drug: tenofovir

standard dosage

Drug: emtricitabine

standard dosage

Drug: abacavir

standard dosage

Detailed Description:

By the end of 2008, we have enrolled 200 patients.

Eligibility

Ages Eligible for Study:	18 Years to 90 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion criteria:

A) Acute HIV-1 infection, defined as:

Acute retroviral syndrome [78] (ARS) and negative or indeterminate Westernblot in the presence of a positive p24 Ag and/or detectable plasma HIV-1 RNA
Documented seroconversion with or without symptoms within 90 days.

or

B) Recent HIV-1 infection, defined as:

Possible ARS, positive Westernblot and detectable HIV-RNA, and a negative HIV-gp120 avidity [82, 83], respectively detuned assay [84].
Documented acute HIV-1 infection, however, referral to our center more than 90 days after presumed date of infection.

Exclusion criteria:

Hemoglobin < 10 g/dl (men) and < 9 g/dl (women) at the time of enrollment.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00537966

Contacts

Contact: Huldrych Günthard, MD

+41 (0)44 255 11 11

Huldrych.Guenthard@usz.ch

Locations

Switzerland
University of Zurich	Recruiting
Zurich, Switzerland
Contact: Huldrych. Günthard Huldrych.guenthard@usz.ch

Sponsors and Collaborators

University of Zurich

Investigators

Principal Investigator:

Huldrych. Günthard, MD

UniversitaetsSpital Zuerich

More Information

Publications:

Rusert P, Kuster H, Joos B, Misselwitz B, Gujer C, Leemann C, Fischer M, Stiegler G, Katinger H, Olson WC, Weber R, Aceto L, Günthard HF, Trkola A. Virus isolates during acute and chronic human immunodeficiency virus type 1 infection show distinct patterns of sensitivity to entry inhibitors. J Virol. 2005 Jul;79(13):8454-69.

Joos B, Trkola A, Fischer M, Kuster H, Rusert P, Leemann C, Böni J, Oxenius A, Price DA, Phillips RE, Wong JK, Hirschel B, Weber R, Günthard HF; Swiss HIV Cohort Study. Low human immunodeficiency virus envelope diversity correlates with low in vitro replication capacity and predicts spontaneous control of plasma viremia after treatment interruptions. J Virol. 2005 Jul;79(14):9026-37.

Aceto L, Karrer U, Grube Ch, Oberholzer R, Hasse B, Presterl E, Böni J, Kuster H, Trkola A, Weber R, Günthard HF. [Primary HIV-1 infection in Zurich: 2002-2004] Praxis (Bern 1994). 2005 Aug 10;94(32):1199-205. German.

Joos B, Trkola A, Kuster H, Aceto L, Fischer M, Stiegler G, Armbruster C, Vcelar B, Katinger H, Günthard HF. Long-term multiple-dose pharmacokinetics of human monoclonal antibodies (MAbs) against human immunodeficiency virus type 1 envelope gp120 (MAb 2G12) and gp41 (MAbs 4E10 and 2F5). Antimicrob Agents Chemother. 2006 May;50(5):1773-9.

Huber M, Fischer M, Misselwitz B, Manrique A, Kuster H, Niederöst B, Weber R, von Wyl V, Günthard HF, Trkola A. Complement lysis activity in autologous plasma is associated with lower viral loads during the acute phase of HIV-1 infection. PLoS Med. 2006 Nov;3(11):e441.

Manrique A, Rusert P, Joos B, Fischer M, Kuster H, Leemann C, Niederöst B, Weber R, Stiegler G, Katinger H, Günthard HF, Trkola A. In vivo and in vitro escape from neutralizing antibodies 2G12, 2F5, and 4E10. J Virol. 2007 Aug;81(16):8793-808. Epub 2007 Jun 13.

Trkola A, Kuster H, Rusert P, von Wyl V, Leemann C, Weber R, Stiegler G, Katinger H, Joos B, Günthard HF. In vivo efficacy of human immunodeficiency virus neutralizing antibodies: estimates for protective titers. J Virol. 2008 Feb;82(3):1591-9. Epub 2007 Nov 21.

Huber M, von Wyl V, Ammann CG, Kuster H, Stiegler G, Katinger H, Weber R, Fischer M, Stoiber H, Günthard HF, Trkola A. Potent human immunodeficiency virus-neutralizing and complement lysis activities of antibodies are not obligatorily linked. J Virol. 2008 Apr;82(8):3834-42. Epub 2008 Jan 30.

Responsible Party:	University Hospital Zurich ( Huldrych Günthard, MD, Professor )
Study ID Numbers:	INFZ-ZPHI-01.01
Study First Received:	September 25, 2007
Last Updated:	May 12, 2009
ClinicalTrials.gov Identifier:	NCT00537966 History of Changes
Health Authority:	Switzerland: Swissmedic

Keywords provided by University of Zurich:

Primary HIV Infection

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Communicable Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Zidovudine
Lamivudine
Infection
Darunavir
Reverse Transcriptase Inhibitors
Tipranavir
Anti-Retroviral Agents
Lopinavir
Emtricitabine

Therapeutic Uses
Tenofovir
Retroviridae Infections
Nucleic Acid Synthesis Inhibitors
Efavirenz
HIV Protease Inhibitors
RNA Virus Infections
Anti-HIV Agents
Immune System Diseases
Acquired Immunodeficiency Syndrome
Enzyme Inhibitors
Atazanavir
Antiviral Agents
Pharmacologic Actions
Immunologic Deficiency Syndromes

ClinicalTrials.gov processed this record on February 08, 2010