Characterization of Acute and Recent HIV-1 Infections in Zurich.

Official title

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

Overview

Aim of the study: To study and to describe factors which could influence the course of primary HIV infection (PHI) and factors that in turn could be influenced through PHI. 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.

Detailed description

The ZPHI is a longitudinal, observational, multi-center study. The ZPHI study started in 2002: The first patient visit (FPFV) was in January 2002. Since then, we continuously enrolled patients fulfilling the inclusion criteria. Because the ZPHI is an observational, longitudinal study and the HIV epidemic in Switzerland evolves continuously a clear study end point is not possible. We plan to critically revise the current protocol every 5 years and at that point, also evaluate whether the study should be continued.

This study so far has been highly successful in the recruitment of patients with a PHI. To date we have enrolled more than 480 patients with a documented PHI since project start in 2002.

Primary outcome measures

• Evaluation of early events between virus and host to better understand HIV-pathogenesis during the early course of HIV infection. [Time frame: 30 years]

Secondary outcome measures (8)

• Systematic Collection and Analysis of Personal Health and Clinical Data [Time frame: 30 Years]
• Systematic Assessment of PHI to Identify Atypical Presentations [Time frame: 30 Years]
• Systematic Screening for Sexually Transmitted Infections (STIs) [Time frame: 30 Years]
• Identification of Transmission Networks for HIV and Acute Hepatitis C [Time frame: 30 Years]
• Investigation of Viral Factors in HIV-1 Pathogenesis [Time frame: 30 Years]
• Analysis of Biological Characteristics of Transmitted Viruses [Time frame: 30 Years]
• Study of HIV-Specific Immune Responses and Innate Immune System Factors [Time frame: 30 Years]
• Genetic Studies Using Next-Generation Sequencing to Investigate Traits Linked to HIV Progression [Time frame: 30 Years]

Eligibility criteria

Inclusion criteria

A) acute HIV-1 infection, defined as:

• negative or evolving immunoblot in the presence of positive p24 Ag and/or detectable plasma HIV-1 RNA and/or
• documented HIV seroconversion within 90 dayswith or with-out symptoms and/or clinical signs of PHI (e.g. acute retro-viral syndrome).

B) recent HIV-1 infection, defined as:

• documented seroconversion of more than 90 days but within 180 days and/or
• evolving immunoblot after unambiguous transmission risk (e.g. iv drug use, sexual contact) within 180 days and/or
• documented HIV infection and unambiguous transmission risk (iv drug use, sexual contact) within 180 days and/or
• documented HIV infection and possible transmission risk (iv drug use, sexual contact) within the last 180 days after infection AND < 0.5% fraction of ambiguous nucleotides

Exclusion criteria

• Documented HIV infection, however, established diagnosis more than 180 days after presumed date of infection.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Switzerland · 1 center

• University of Zurich — Zurich

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, Gunthard 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. doi: 10.1128/JVI.79.13.8454-8469.2005. PMID 15956589
• Joos B, Trkola A, Fischer M, Kuster H, Rusert P, Leemann C, Boni J, Oxenius A, Price DA, Phillips RE, Wong JK, Hirschel B, Weber R, Gunthard 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. doi: 10.1128/ PMID 15994796
• Aceto L, Karrer U, Grube Ch, Oberholzer R, Hasse B, Presterl E, Boni J, Kuster H, Trkola A, Weber R, Gunthard HF. [Primary HIV-1 infection in Zurich: 2002-2004]. Praxis (Bern 1994). 2005 Aug 10;94(32):1199-205. doi: 10.1024/0369-8394.94.32.1199. German. PMID 16128207
• Joos B, Trkola A, Kuster H, Aceto L, Fischer M, Stiegler G, Armbruster C, Vcelar B, Katinger H, Gunthard 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. doi: 10.1128/AAC.50.5.1773-1779.2006. PMID 16641449
• Huber M, Fischer M, Misselwitz B, Manrique A, Kuster H, Niederost B, Weber R, von Wyl V, Gunthard 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. doi: 10.1371/journal.pmed.0030441. PMID 17121450
• Manrique A, Rusert P, Joos B, Fischer M, Kuster H, Leemann C, Niederost B, Weber R, Stiegler G, Katinger H, Gunthard HF, Trkola A. In vivo and in vitro escape from neutralizing antibodies 2G12, 2F5, and 4E10. J Virol. 2007 Aug;81(16):8793-808. doi: 10.1128/JVI.00598-07. Epub 2007 Jun 13. PMID 17567707
• Trkola A, Kuster H, Rusert P, von Wyl V, Leemann C, Weber R, Stiegler G, Katinger H, Joos B, Gunthard HF. In vivo efficacy of human immunodeficiency virus neutralizing antibodies: estimates for protective titers. J Virol. 2008 Feb;82(3):1591-9. doi: 10.1128/JVI.01792-07. Epub 2007 Nov 21. PMID 18032508
• Huber M, von Wyl V, Ammann CG, Kuster H, Stiegler G, Katinger H, Weber R, Fischer M, Stoiber H, Gunthard 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. PMID 18234794

Identifiers

NCT: NCT00537966 · INFZ-ZPHI-01.01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗