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

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

Patients with primary HIV-1 infection who do not want to undergo early combination antiretroviral treatment

In this arm patients with primary HIV-1 infection will receive early combination antiretroviral therapy with standard drugs approved by Swiss Medic.

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)

used only as booster for the protease inhibitors that are prescribed in this study according to standard boosting

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.

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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.

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