Clinical trial NCT00537966: 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.
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: HIV Infections
Keywords: Primary HIV Infection
Lead sponsor: University of Zurich
Sponsor class: OTHER
First posted: 2007-10-02
Enrollment: 800
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Men and women \> 18 years with a documented acute or recent HIV-1 infection.

Brief summary: 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.

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.

Primary outcomes:
measure: Evaluation of early events between virus and host to better understand HIV-pathogenesis during the early course of HIV infection.
timeFrame: 30 years
Secondary outcomes:
measure: Systematic Collection and Analysis of Personal Health and Clinical Data
timeFrame: 30 Years
measure: Systematic Assessment of PHI to Identify Atypical Presentations
timeFrame: 30 Years
measure: Systematic Screening for Sexually Transmitted Infections (STIs)
timeFrame: 30 Years
measure: Identification of Transmission Networks for HIV and Acute Hepatitis C
timeFrame: 30 Years
measure: Investigation of Viral Factors in HIV-1 Pathogenesis
timeFrame: 30 Years
measure: Analysis of Biological Characteristics of Transmitted Viruses
timeFrame: 30 Years
measure: Study of HIV-Specific Immune Responses and Innate Immune System Factors
timeFrame: 30 Years
measure: Genetic Studies Using Next-Generation Sequencing to Investigate Traits Linked to HIV Progression
timeFrame: 30 Years
Other outcomes:
Locations:
city: Zurich
country: Switzerland
facility: University of Zurich
Study officials:
affiliation: UniversitaetsSpital Zuerich
name: Huldrych. Günthard, MD
role: PRINCIPAL_INVESTIGATOR
References:
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, 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.
citation: 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/JVI.79.14.9026-9037.2005.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: Ring A, Balakrishna S, Imkamp F, Burkard S, Triet F, Brunschweiler F, Grube C, Bodmer R, Kouyos RD, Gunthard HF, Braun DL. High Rates of Asymptomatic Mycoplasma genitalium Infections With High Proportion of Genotypic Resistance to First-Line Macrolide Treatment Among Men Who Have Sex With Men Enrolled in the Zurich Primary HIV Infection Study. Open Forum Infect Dis. 2022 Apr 27;9(6):ofac217. doi: 10.1093/ofid/ofac217. eCollection 2022 Jun.
citation: Rindler AE, Kusejko K, Kuster H, Neumann K, Leemann C, Zeeb M, Chaudron SE, Braun DL, Kouyos RD, Metzner KJ, Gunthard HF. The Interplay Between Replication Capacity of HIV-1 and Surrogate Markers of Disease. J Infect Dis. 2022 Sep 21;226(6):1057-1068. doi: 10.1093/infdis/jiac100.
citation: Braun DL, Marzel A, Steffens D, Schreiber PW, Grube C, Scherrer AU, Kouyos RD, Gunthard HF; Swiss HIV Cohort Study. High Rates of Subsequent Asymptomatic Sexually Transmitted Infections and Risky Sexual Behavior in Patients Initially Presenting With Primary Human Immunodeficiency Virus-1 Infection. Clin Infect Dis. 2018 Feb 10;66(5):735-742. doi: 10.1093/cid/cix873.
citation: Bastidas S, Graw F, Smith MZ, Kuster H, Gunthard HF, Oxenius A. CD8+ T cells are activated in an antigen-independent manner in HIV-infected individuals. J Immunol. 2014 Feb 15;192(4):1732-44. doi: 10.4049/jimmunol.1302027. Epub 2014 Jan 20.
citation: Metzner KJ, Leemann C, Di Giallonardo F, Grube C, Scherrer AU, Braun D, Kuster H, Weber R, Guenthard HF. Reappearance of minority K103N HIV-1 variants after interruption of ART initiated during primary HIV-1 infection. PLoS One. 2011;6(7):e21734. doi: 10.1371/journal.pone.0021734. Epub 2011 Jul 6.