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

Study Overview
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Brief Summary
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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

Detailed Description
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By the end of 2017 we have enrolled 450 patients.

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

Conditions
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HIV Infections

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control<br>Patients with primary HIV-1 infection who do not want to undergo early combination antiretroviral treatment | |
| Active Comparator: Intervention<br>In this arm patients with primary HIV-1 infection will receive early combination antiretroviral therapy with standard drugs approved by Swiss Medic. | Drug: Dolutegravir<br>* 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)<br>* Other names: Tivicay;Drug: Elvitegravir, Cobicistat, Emtricitabine, and Tenofovir Alafenamid Fumarate<br>* standard dosage<br>* Other names: Genvoya;Drug: Raltegravir<br>* standard dosage<br>* Other names: isentress;Drug: Darunavir<br>* standard dosage<br>* Other names: Prezista;Drug: Ritonavir<br>* used only as booster for the protease inhibitors that are prescribed in this study according to standard boosting<br>* Other names: Norvir;Drug: Rilpivirine<br>* standard dosage<br>* Other names: Edurant;Drug: Lamivudine<br>* standard dosage<br>* Other names: 3TC;Drug: tenofovir<br>* standard dosage<br>* Other names: Viread;Drug: Emtricitabine<br>* standard dosage<br>* Other names: Emtriva;Drug: Abacavir<br>* standard dosage<br>* Other names: Ziagen;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the effect of early-cART on the viral setpoint |  | 2016 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Primary HIV Infection