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

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

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.

Study Overview

• Status: Recruiting
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Dolutegravir; Drug: Elvitegravir, Cobicistat, Emtricitabine, and Tenofovir Alafenamid Fumarate; Drug: Raltegravir; Drug: Darunavir; Drug: Ritonavir; Drug: Rilpivirine; Drug: Lamivudine; Drug: tenofovir; Drug: Emtricitabine; Drug: Abacavir

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.

• Study Type: Observational
• Enrollment (Estimated): 800
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Huldrych Günthard, MD; Phone Number: +41 (0)44 255 11 11; Email: Huldrych.Guenthard@usz.ch

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Men and women > 18 years with a documented acute or recent HIV-1 infection.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Primo - Cohort; The patients with primary HIV-1 infection will receive combination antiretroviral therapy with standard drugs approved by Swiss Medic.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of early events between virus and host to better understand HIV-pathogenesis during the early course of HIV infection.	The enrolment and the longitudinal follow up of patients with a documented PHI will allow us to study early events between virus and host and to better understand HIV-pathogenesis during the early course of HIV infection. We aim to expand the established biobank in order to collect samples from patients with an acute or recent HIV infection: For the biobank, we will collect blood samples which are obtained in addition to the routinely collected clinical samples. This concerns ETDA blood samples, initially collected every 3 months until week 48, followed by every six months until week 240 and thereafter once yearly from week 240 onwards. Moreover, a stool sample will be collected and stored for research purposes only. In addition, we will store routinely collected CSF, STI swabs (rectal, virginal, urethral, pharyngeal), urethral swabs, stool samples and in case of high-resolution anoscopy also rectal biopsy materialin the biobanks of the accoding institutes.	30 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Systematic Collection and Analysis of Personal Health and Clinical Data	Secondary Outcome: Number of participants with complete health and clinical datasets analyzed.; Unit of Measure: Count of datasets.	30 Years
Systematic Assessment of PHI to Identify Atypical Presentations	Secondary Outcome: Percentage of participants presenting atypical symptoms of PHI.; Unit of Measure: Percentage.	30 Years
Systematic Screening for Sexually Transmitted Infections (STIs)	Secondary Outcome: Number of STI cases identified, classified by clinical characteristics and resistance patterns.; Unit of Measure: Count of cases	30 Years
Identification of Transmission Networks for HIV and Acute Hepatitis C	Secondary Outcome: Number of transmission clusters identified through phylogenetic analysis.; Unit of Measure: Count of clusters.	30 Years
Investigation of Viral Factors in HIV-1 Pathogenesis	Secondary Outcome: Percentage of patient samples with drug-resistant variants, viral diversity, or replication capacity metrics.; Unit of Measure: Percentage or specific diversity/replication scores.	30 Years
Analysis of Biological Characteristics of Transmitted Viruses	Secondary Outcome: Replication capacity of transmitted viruses; Unit of Measure: Replication cycles/hour	30 Years
Study of HIV-Specific Immune Responses and Innate Immune System Factors	Secondary Outcome: Concentration of immune markers, such as cytokine levels, associated with specific immune responses.; Unit of Measure: Concentration (pg/mL).	30 Years
Genetic Studies Using Next-Generation Sequencing to Investigate Traits Linked to HIV Progression	Secondary Outcome: Number of genetic polymorphisms associated with differential progression in natural HIV infection.; Unit of Measure: Count of identified polymorphisms.	30 Years

Collaborators and Investigators

• Sponsor: University of Zurich
• Investigators: Principal Investigator: Huldrych. Günthard, MD, Universitaetsspital Zuerich

Publications and helpful links

General 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: January 1, 2002
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: September 25, 2007
• First Submitted That Met QC Criteria: October 1, 2007
• First Posted (Estimated): October 2, 2007

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 12, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Primary HIV Infection
• Additional Relevant MeSH Terms: Blood-Borne Infections; Urogenital Diseases; Genital Diseases; Pathologic Processes; Disease Attributes; Immune System Diseases; RNA Virus Infections; Virus Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Infections; Communicable Diseases; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Integrase Inhibitors; Integrase Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Tenofovir; Emtricitabine; Cobicistat; Raltegravir Potassium; Ritonavir; Lamivudine; Darunavir; Dolutegravir; Rilpivirine; Abacavir; Elvitegravir
• Other Study ID Numbers: INFZ-ZPHI-01.01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No