Characterization of Acute and Recent HIV-1 Infections in Zurich: a Long-term Observational Study

HIV Infections Clinical Trial

Official title:

Characterization of Acute and Recent HIV-1 Infections in Zurich: a Long-term Observational Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00537966
• Other study ID #: INFZ-ZPHI-01.01
• Status: Recruiting
• Phase: N/A
• First received: September 25, 2007
• Last updated: November 7, 2017
• Start date: January 2002
• Est. completion date: January 2025

Study information

• Verified date: November 2017
• Source: University of Zurich
• Contact: Huldrych Günthard, MD
• Phone: +41 (0)44 255 11 11
• Email: Huldrych.Guenthard[@]usz.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

By the end of 2017 we have enrolled 450 patients.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2017
• Est. completion date: January 2025
• Est. primary completion date: January 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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.

Related Conditions & MeSH terms

• Communicable Diseases
• HIV Infections
• Infection

Intervention

Drug:
• Dolutegravir
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)
• Elvitegravir, Cobicistat, Emtricitabine, and Tenofovir Alafenamid Fumarate
standard dosage
• Raltegravir
standard dosage
• Darunavir
standard dosage
• Ritonavir
used only as booster for the protease inhibitors that are prescribed in this study according to standard boosting
• Rilpivirine
standard dosage
• Lamivudine
standard dosage
• tenofovir
standard dosage
• Emtricitabine
standard dosage
• Abacavir
standard dosage

Locations

Country	Name	City	State
Switzerland	University of Zurich	Zurich

Sponsors (1)

Lead Sponsor	Collaborator
University of Zurich

Country where clinical trial is conducted

Switzerland, 

References & Publications (8)

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. — View Citation

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. — View Citation

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. doi: 10.1128/JVI.02569-07. Epub 2008 Jan 30. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To evaluate the effect of early-cART on the viral setpoint		2016