Characterization of Acute and Recent HIV-1 Infections in Zurich: a Long-Term Observational Study
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...
Brief Summary
Official Title: “Characterization of Acute and Recent HIV-1 Infections in Zurich: a Long-Term Observational Study”
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
- Study Type: Interventional
- Study Design: Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
- Study Primary Completion Date: December 2015
Detailed Clinical Trial Description
By the end of 2008, we have enrolled 200 patients.
Intervention(s) in this Clinical Trial
- 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, Groups and Cohorts in this Clinical Trial
- No Intervention: Control
- Patients with primary HIV-1 infection who do not want to undergo early combination antiretroviral treatment
- Active Comparator: Intervention
- In this arm patients with primary HIV-1 infection will receive early combination antiretroviral therapy with standard drugs approved by Swiss Medic.
Outcome Measures for this Clinical Trial
Primary Measures
- To evaluate the effect of early-cART on the viral setpoint
- Time Frame: 2016
Safety Issue?: No
- Time Frame: 2016
Criteria for Participation in this Clinical Trial
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.
Gender Eligibility for this Clinical Trial: Both
Minimum Age for this Clinical Trial: 18 Years
Maximum Age for this Clinical Trial: 90 Years
Are Healthy Volunteers Accepted for this Clinical Trial?: No
Clinical Trial Investigator Information
Lead Investigator: University of Zurich Other
Overall Clinical Trial Officials and Contacts
Huldrych. Günthard, MD Principal Investigator UniversitaetsSpital Zuerich
Overall Contact: Huldrych Günthard, MD +41 (0)44 255 11 11 Huldrych.Guenthard@usz.ch
Related Publications
References
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.
Additional Information
Information obtained from ClinicalTrials.gov on February 12, 2012
Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00537966
Study ID Number: INFZ-ZPHI-01.01
ClinicalTrials.gov Identifier: NCT00537966
Health Authority: Switzerland: Swissmedic
Clinical Trials content is provided directly by the U.S. National Institutes of Health via ClinicalTrials.gov and is not reviewed separately by ClinicalTrialsFeeds.org. Every page of specific clinical trials information contains a unique identifier which can be used to find further details directly from the National Institutes of Health.
The URL of this page is:
http://clinicaltrialsfeeds.org/clinical-trials/show/NCT00537966
