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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 3

Evidence of clonal expansion in Pt169 and ES24.

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Evidence of clonal expansion in Pt169 and ES24.
(A and B) Percentage of ...
(A and B) Percentage of clonal integration sites for (A) Pt169 and (B) ES24. (C) Frequency of identical proviral env amplified from ESs (8 subjects, median number of clones sequenced 10.5, range 4–14), ART-treated individuals (9 subjects, median number of clones sequenced 30, range 7–44), and viremic individuals (7 subjects, median number of clones sequenced 15, range 12–19). The center line indicates the mean, and error bars show standard deviation. Statistical analysis was done using a 1-way ANOVA with Tukey’s multiple comparison test. ***P < 0.001.

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