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Antiretroviral therapy fails to cure HIV-1 infection because latent proviruses persist in resting CD4(+) T cells. T cell activation reverses latency, but <1% of proviruses are induced to release infectious virus after maximum in vitro activation. The noninduced proviruses are generally considered defective but have not been characterized. Analysis of 213(More)
Rare human immunodeficiency virus 1-infected individuals, termed elite suppressors (ES), maintain plasma virus levels of <50 copies/ml and normal CD4 counts without therapy. The major histocompatibility complex class I allele group human histocompatibility leukocyte antigen (HLA)-B*57 is overrepresented in this population. Mutations in HLA-B*57-restricted(More)
HIV-1 persists in infected individuals in a stable pool of resting CD4(+) T cells as a latent but replication-competent provirus. This latent reservoir is the major barrier to the eradication of HIV-1. Clinical trials are currently underway investigating the effects of latency-disrupting compounds on the persistence of the latent reservoir in infected(More)
HIV-1-infected elite controllers or suppressors (ES) maintain undetectable viral loads (< 50 copies/mL) without antiretroviral therapy. The mechanisms of suppression are incompletely understood. Modulation of HIV-1 replication by miRNAs has been reported, but the role of small RNAs in ES is unknown. Using samples from a well-characterized ES cohort,(More)
Innate immune sensing of viral infection results in type I interferon (IFN) production and inflammasome activation. Type I IFNs, primarily IFN-α and IFN-β, are produced by all cell types upon virus infection and promote an antiviral state in surrounding cells by inducing the expression of IFN-stimulated genes. Type I IFN production is mediated by Toll-like(More)
Elite suppressors are untreated individuals with human immunodeficiency virus type 1 (HIV-1) infection who maintain viral loads <50 copies/mL. Using a single-copy assay, we show that there is no statistically significant difference between the proportions of elite suppressors and patients receiving suppressive highly active antiretroviral therapy who have(More)
Elite suppressors or controllers (ES) are HIV-1 infected patients who maintain undetectable viral loads without treatment. While HLA-B*57-positive ES are usually infected with virus that is unmutated at CTL epitopes, a single, dominant variant containing CTL escape mutations is typically seen in plasma during chronic infection. We describe an ES who(More)
Elite controllers or suppressors have the remarkable capacity to maintain HIV-1 plasma RNA levels below the limit of detection of clinical assays (<50 copies/mL) without therapy and have a lower frequency of latently infected cells compared to chronic progressors. While it is unclear how this reduced seeding of the reservoir is achieved, it is possible that(More)
Viremic controllers and elite controllers/suppressors maintain control over HIV-1 replication. Some studies have suggested that control is a result of infection with a defective viral strain, while others suggested host immune factors have a key role. Here we document two HIV-1 transmission pairs: one consisting of a patient with progressive disease and an(More)
We report a case of a patient infected with human immunodeficiency virus type 1 (HIV-1) for 20 years who has experienced CD4(+) T cell depletion in spite of maintaining undetectable viral loads. Our data suggest that immune activation can cause CD4(+) T cell depletion even when HIV-1 replication appears to be controlled by host factors.