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1277 Results
Background Multi-omics data integration offers potential to uncover hidden patterns among people living with HIV (PLWH). This study aimed to identify clusters of individuals with distinct viral reservoir characteristics and multi-omics profiles in the 2000HIV cohort. Methods Multi-omics data from 1,236 PLWH in the 2000HIV cohort (NCT03994835) were analyzed, including gene expression (58,347 genes, bulk…
Background Most methods of amplifying and sequencing proviruses do not capture the flanking long terminal repeats (LTRs) because of technical difficulties related to sequence identity between these elements. Consequently, defective HIV-1 proviruses consisting of a single LTR (solo-LTR), a common proviral structure across retroviruses, are not detected and thus their frequency and significance are poorly…
Background Mitochondria are crucial for cellular energy metabolism and immune regulation, but their role in spontaneous HIV control remains unclear. We hypothesized that single nucleotide polymorphisms (SNPs) in mitochondrial-related genes influence HIV control. Methods SNP-set enrichment analysis was conducted to determine if SNPs in autosomal mitochondrial-related genes are enriched in HIV-control associated SNPs compared to…
Background In people living with HIV on suppressive ART, the latent reservoir is composed of archived viral variants that are either sensitive or resistant to autologous neutralizing antibodies (aNAbs), with the latter capable of causing rebound following treatment interruption. We hypothesized ART-free virologic control might be achieved if aNAbs developed to neutralize all inducible, replication-competent…
Background The HIV reservoir persists within clonally expanded CD4+ T cells carrying intact proviruses. We describe the isolation and long-term in vitro expansion of these ‘authentic reservoir clones’ (ARCs) and insights into functional characteristics that may underlie their persistence. Methods Authentic reservoir clones (ARCs) were derived from CD4+ memory T cells (n=4) using multiple rounds…
Background Natural protection against CCR5-tropic HIV-1 variants is attributed to the presence of CCR5Δ32. We aimed to identify genetic and non-genetics and factors influencing CCR5 expression on CD4+ and CD8+ T cells and to assess the role of CCR5 expression in maintaining HIV control status and reservoir size in people living with HIV (PLHIV). Methods…
Background Both HTLV-1 and HIV-1 cause a lifelong incurable infection, but mechanisms of viral persistence may vary. In HIV-1 infection, prior data demonstrated a progressive accumulation of intact proviruses in heterochromatin during long-term ART, likely as a result of immune-mediated selection that promotes viral persistence in repressive chromatin. Whether and how proviral integration site locations…
Background While early ART initiation has been associated with smaller HIV reservoirs, it is not clear how the timing of ART initiation affects subsets of the “active” HIV-transcribing reservoir. Methods We compared temporal changes in various proviruses and HIV transcripts in CD4+T cells isolated from longitudinal blood samples obtained before ART (T1) and at two…
Background HIV elite control in the absence of therapy is marked by a highly clonal integration site landscape. However, the underlying mechanisms remain elusive, impeding the design of therapies that could replicate this exceptional HIV control. We previously demonstrated that elite controller CD8+ T cells reduced HIV integration site diversity, decreased genic integrations, and enriched for…
Background It remains unclear how HIV transcription varies with timing of ART initiation, duration of ART, and elite controller status. Methods To investigate these questions, we performed a blinded, cross-sectional analysis of 98 PBMC samples from 36 Reservoir Assay Validation and Evaluation Network (RAVEN) program participants, including 4 ART-naïve elite controllers and 32 ART-suppressed participants with HIV…