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1277 Results
Background A major challenge in curing HIV is eliminating latent integrated proviral DNA from CD4+ T and myeloid cells. Recent clinical studies (EBT-101) using adeno-associated viral (AAV) vectors to deliver CRISPR for HIV eradication remained unsuccessful likely due to the limitations of AAV vectors, highlighting the need for alternative delivery systems like lipid nanoparticles (LNPs). To this end,…
Background HIV reservoirs in CD4⁺ T cells may be selected for the ability to evade immune clearance, hindering HIV cure efforts. Overexpression of enhancer of zeste homolog 2 (EZH2) in HIV-infected CD4⁺ T cells that survive cytotoxic T lymphocyte (CTL) exposure suggests a putative mechanism of immune resistance. This study investigated whether inhibition of EZH2…
Background A cure for HIV remains elusive as the excision of latent proviral DNA by adenovirus-based therapeutic systems has failed to date due to vector immunogenicity and limited targeting to viral reservoirs. In contrast, lipid nanoparticles (LNPs) are promising for targeting viral reservoirs, offering greater cargo-carrying capacity and reduced immune responses. However, limitations in endosomal…
Background Intact proviral DNA assays (IPDA) are high-throughput methods to quantify intact and defective HIV proviruses during ART, with the former providing estimates of rebound-competent HIV reservoir. However, most IPDAs have been designed for subtype B and have ~28% false negative rate due to polymorphisms in the primer/probe sites1. The cross-subtype IPDA (CS-IPDA) was designed…
Background The male genital tract (MGT) is a crucial site for transmission of HIV and co-infecting viruses and functions as an immune-privileged area and key reservoir for HIV, where viral replication can persist despite suppressive ART. The MGT also hosts a distinct microbiota, which may influence viral dynamics and HIV persistence. While previous studies have…
Background Viral reservoir presents a significant challenge in HIV-1 cure. Studies indicate that dendritic cells may limit HIV-1 reservoir by bolstering CD8+ T cell function via the IL-15 pathway and facilitating the expansion of virtual memory CD8+ T cells (TVM). We previously observed that Thymosin α1 (Tα1) may restrict the reservoir through the IL-15 pathway,…
Background Despite the cumulative expansion of the viral reservoir during untreated HIV-1 infection, it has been recently observed that the intact variants dated close to time of ART initiation predominate in the replicative-competent reservoir. This observation indicates that there is a critical window period immediately following ART initiation that significantly shapes the composition of the…
Background There is a global need to explore novel interventions conferring sustained HIV control without antiretroviral therapy (ART). The only current strategy to test efficacy is through an analytical treatment interruption (ATI). Inclusion of ‘placebo’ controls in future clinical trials poses ethical, logistical, and economic challenges and might be unnecessary if sufficient up-to-date data exists…
Background Despite the efficacy of ART, HIV-1 persistence in reservoirs, mostly formed by CD4 and macrophages hinders eradication. Nuclear import of pre-integration complex is assisted by proteins from mRNA processing pathways like CPSF6 (3´RNA-cleavage and polyadenylation factor 6) and SRSF2/SC35 (Serine/Arginine-rich splicing factor 2). Dasatinib and ponatinib are tyrosine kinase inhibitors (TKIs) that interfere with HIV-1…
Background Long-term antiretroviral therapy (ART) in people with HIV (PWH) has been related to reduced levels of competent proviruses. We aimed to evaluate how time on ART affects reservoir size, reactivation capacity and cytotoxic response. Methods Cross-sectional study with 64 PWH who were on ART for <1 year (<1y)(n=11), 1 to 10 years (1-10y)(n=20), 10…