Browsing by Author "Sereti, Irini"

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    Comprehensive analysis of unique cases with extraordinary control over HIV replication
    (2012) Mendoza, Daniela; Johnson, Sherry A.; Peterson, Brenda A.; Natarajan, Vanitha; Salgado, Marcela; Dewar, Rebecca L.; Burbelo, Peter D.; Doria-Rose, Nicole A.; Graf, Erin H.; Greenwald, Jamieson H.; Hodge, Jessica N.; Thompson, William L.; Cogliano, Nancy A.; Chairez, Cheryl L.; Rehm, Catherine A.; Jones, Sara; Hallahan, Claire W.; Kovacs, Joseph A.; Sereti, Irini; Sued, Omar; Peel, Sheila A.; O'Connell, Robert J.; O'Doherty, Una; Chun, Tae-Wook; Connors, Mark; Migueles, Stephen A.
    True long-term nonprogressors (LTNPs)/elite controllers (ECs) maintain durable control over HIV replication without antiretroviral therapy. Herein we describe 4 unique persons who were distinct from conventional LTNPs/ECs in that they had extraordinarily low HIV burdens and comparatively weak immune responses. As a group, typical LTNPs/ECs have unequivocally reactive HIV-1 Western blots, viral loads below the lower threshold of clinical assays, low levels of persistent viral reservoirs, an over-representation of protective HLA alleles, and robust HIV-specific CD8+ T-cell responses. The 4 unique cases were distinguished from typical LTNPs/ECs based on weakly reactive Western blots, undetectable plasma viremia by a single copy assay, extremely low to undetectable HIV DNA levels, and difficult to isolate replication-competent virus. All 4 had at least one protective HLA allele and CD8+ T-cell responses that were disproportionately high for the low antigen levels but comparatively lower than those of typical LTNPs/ECs. These unique persons exhibit extraordinary suppression over HIV replication, therefore, higher-level control than has been demonstrated in previous studies of LTNPs/ECs. Additional insight into the full spectrum of immune-mediated suppression over HIV replication may enhance our understanding of the associated mechanisms, which should inform the design of efficacious HIV vaccines and immunotherapies.
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    HIV and aging, biological mechanisms, and therapies: What do we know?
    (Permanyer Publications, 2022) Grosso, Tomás M.; Alcamí, José; Arribas, Jose; Martín, Marta; Sereti, Irini; Tarr, Philip; Cahn, Pedro; Clotet, Bonaventura; Sued, Omar; Negredo, Eugenia
    Aging, a time-dependent loss of physiological function, and its drivers are turning into a significant topic of research as the population's mean age increases. Epigenetic alterations, telomere shortening or dysfunction, mitogenic stress, oxidative stress, or accumulation of DNA damage can drive the cell to senescence: a permanent cell cycle arrest sometimes associated with a secretory phenotype and inflammatory consequences in the surrounding tissue. The amount of senescent cells grows over time in older organisms and may induce tissue inflammation and threaten overall tissue homeostasis, favoring aging. Senolytic and senomorphic therapeutics are an emerging approach to eliminate senescent cells or to block their secretory phenotypes respectively. Given that people living with HIV suffer non-AIDS comorbidities in a higher prevalence than the general population, aging is accentuated among them. Inflammation biomarkers may be helpful to assess prognosis or act as surrogate endpoints for studies of strategies focused on reversal of HIV-associated accelerated aging. This review summarizes the latest findings in aging and its major drivers, under the light of HIV infection. Since the number of older PLWH is currently rising, it will be of great importance to address and treat their age-related conditions, as well as to better decipher their biological mechanisms.