Results of Combination Antibody Therapy in Long-Term Viral Suppression of HIV Infection



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A new generation of largely neutralizing antibodies offers a new approach to treating HIV infection. The research group of Prof. Florian Klein, director of the Institute of Virology at the University Hospital of Cologne and scientist of the German Infection Research Center (DZIF), collaborated with scientists from the University of Cologne. Rockefeller University of New York and the University Hospital of Cologne. the impact of the combination of these antibodies in patients infected with HIV. Two articles on the results of this clinical trial were published in Natureand Medicine of nature.

Antiretroviral drugs are the essential component of an effective management of HIV infection. Due to the rapid development of viral resistance against single agents, these drugs must be administered in combination. Although currently approved drugs are highly active inhibitors of viral replication, they require a daily dosage and lifetime.

Compared to antiretroviral drugs, the largely neutralizing antibodies have a longer half-life and can directly target the virus. In previous clinical trials with the participation of the University Hospital Cologne, two of these antibodies, called 3BNC117 and 10-1074, were administered individually. Both antibodies were well tolerated and resulted in significant reductions in viral load. However, like classical antiretroviral therapy, the administration of a single antibody has only had transient effects on the viral load and has been associated with the ## 147 ## # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # # 39, appearance of viral resistance.

In this study, scientists studied the administration of the combination of 3BNC117 and 10-1074 antibodies in a total of 30 HIV-infected individuals. Infusions of antibodies, administered up to three times per individual, were well tolerated by all study participants. In the group of HIV-infected participants who were not taking antiretroviral drugs at the start of the trial, the combination of antibodies resulted in substantial reductions in viral load.

In a second group, the antibody combination was administered to individuals who had discontinued their previous treatment with regular antiretrovirals. Although this interruption usually results in a rapid return of HIV to the blood, no viraemia was detected in many participants for several months after the last infusion of the combination of antibodies.

"The results of this clinical trial highlight the potential of antibody combinations to maintain long-term control of HIV," says Dr. Henning Grüll, co-lead author of the publications and medical resident of the US. Institute of Virology of the University Hospital of Cologne. Based on the results of a study conducted with Rockefeller University (Prof. Michel Nussenzweig, Prof. Marina Caskey), new approaches to antibody-mediated treatment of HIV infections may provide long-term control. term virus without the need for daily medication.

"The success of these studies at the University Hospital Cologne is also the result of close collaboration with the Research Group on Infectious Diseases (led by Professor Gerd Fätkenheuer) and the Clinic of Infectious Diseases ( led by Dr. Clara Lehmann), we were able to safely and quickly translate the results of basic research into clinical applications, "says Florian Klein, lead researcher for the study in Germany.

Other clinical trials involving additional approaches to the use of largely neutralizing antibodies in HIV infection are currently underway at the DZIF site in Cologne.

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