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Long-term remission despite clonal expansion of replication-competent HIV-1 isolates
Rebecca T. Veenhuis, … , Frederic D. Bushman, Joel N. Blankson
Rebecca T. Veenhuis, … , Frederic D. Bushman, Joel N. Blankson
Published September 20, 2018
Citation Information: JCI Insight. 2018;3(18):e122795. https://doi.org/10.1172/jci.insight.122795.
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Research Article AIDS/HIV

Long-term remission despite clonal expansion of replication-competent HIV-1 isolates

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Abstract

Clonal expansion of T cells harboring replication-competent virus has recently been demonstrated in patients on suppressive antiretroviral therapy (ART) regimens. However, there has not been direct evidence of this phenomenon in settings of natural control, including in posttreatment controllers who maintain control of viral replication after treatment when ART is discontinued. We present a case of an individual who has had undetectable viral loads for more than 15 years following the cessation of ART. Using near-full-genome sequence analysis, we demonstrate that 9 of 12 replication-competent isolates cultured from this subject were identical and that this identity was maintained 6 months later. A similar pattern of replication-competent virus clonality was seen in a treatment-naive HLA-B*57 elite controller. In both cases, we show that CD8+ T cells are capable of suppressing the replication of the clonally expanded viruses in vitro. Our data suggest that, while clonal expansion of replication-competent virus can present a barrier to viral eradication, these viral isolates remain susceptible to HIV-specific immune responses and can be controlled in patients with long-term suppression of viral replication.

Authors

Rebecca T. Veenhuis, Abena K. Kwaa, Caroline C. Garliss, Rachel Latanich, Maria Salgado, Christopher W. Pohlmeyer, Christopher L. Nobles, John Gregg, Eileen P. Scully, Justin R. Bailey, Frederic D. Bushman, Joel N. Blankson

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Figure 2

Large degree of clonality in ES24 replication-competent and proviral full-length env and nef sequences.

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Large degree of clonality in ES24 replication-competent and proviral ful...
Phylogenetic trees of near-full-length replication-competent virus (A) and full-length env (B) and nef (C) from either proviral clones (triangles) or replication-competent virus (circles). Boxes indicate identical sequences.

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