La Dra. Katharine Barr, quien participa en la sesión inaugural, nos habla sobre el reservorio del VIH y otras cuestiones relacionadas con los últimos avances y descubrimientos.
Katharine Bar is an assistant professor at the University of Pennsylvania and an Infectious Diseases physician, clinical trialist and physician-scientist who studies the basic mechanisms and translational impact of virus transmission, pathogenesis and persistence of HIV-1, SARS-CoV -2 and other viral pathogens.
After completing a residency in internal medicine at the Virginia Hospitals School of Medicine, where she was chief resident, and a fellowship focused on infectious diseases at the University of Alabama Hospital, Bar joined the faculty at the University of Pennsylvania, where she directs the Center for AIDS Research Virology Core. She has dedicated her career to pursuing prevention and cure strategies for HIV and AIDS.
Will we achieve a treatment that cures HIV?
There are recent discoveries that support the development of new cure strategies.
What are these latest discoveries?
First, studies suggest examining the reservoir over time suggest that the human immune system remains active over years of ART suppression. These include reports that people with long-term ART, the intact viral reservoir declines faster than the defective reservoir. Similarly in Elite Controllers, reservoirs become more “deeply latent” over time, indicating that more active reservoirs have been cleared. This provides encouragement that our immune systems can identify and clear some reservoirs. With additional help, through immunotherapy or through vaccination, this clearance may be far more effective. Studies of reservoir formation indicate that the reservoir can be formed from very early infection through the time of ART initiation. Several studies suggest that reservoir is proportionally enriched for cells infected at the time of ART initiation. Thus, there is a wave of enthusiasm to try to “block” reservoir formation with interventions (like antibodies or anti-proliferative agents) at the time of starting antiretrovirals. Indeed, the eCLEAR study (published in 2022) suggested that broadly neutralizing antibodies given at the time of ART initiation could enhance virus clearance, improve anti-HIV immunity, and perhaps improve virus control after treatment interruptions.
Thus, the field has trials for several promising interventions…
Therapeutic vaccinations aimed to improve CD8 T cell responses have shown signals of efficacy. Several of these vaccines are also being tested in combination with latency reversal agents to provide more antigen to drive immune responses and/or with broadly neutralizing antibodies to better control the virus as adaptive responses build. Therapeutic vaccines aiming to generate broadly neutralizing antibody responses are earlier in development, with several Phase 1 studies currently in the field. At the time of ART initiation, the field is exploring broadly neutralizing antibodies to both clear virus-infected cells and to boost HIV-specific immune responses through a vaccinal effect. There are also studies using antiproliferative agents at ART initiation to try to prevent proliferation of HIV-infected cells. Researchers are also working to enhance virus-infected cell clearance through immunotherapy to enhance cell trafficking or cytotoxicity, or with gene therapy approaches to modify cells to more effectively and specifically identify and clear HIV-expressing cells. Together, these approaches hold promise to advance the HIV cure field.