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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalJCI insight
Volume3
Issue number18
DOIs
StatePublished - Sep 20 2018

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HIV-1
Virus Replication
T-Lymphocytes
Therapeutics
Viral Load
Sequence Analysis
HIV
Genome
Viruses

Keywords

  • AIDS vaccine
  • AIDS/HIV
  • T cells

Cite this

Long-term remission despite clonal expansion of replication-competent HIV-1 isolates. / Terilli Veenhuis, Rebecca; Kwaa, Abena K.; Garliss, Caroline C.; Latanich, Rachel; Salgado, Maria; Pohlmeyer, Christopher W.; Nobles, Christopher L.; Gregg, John; Scully, Eileen; Bailey, Justin; Bushman, Frederic D.; Blankson, Joel N.

In: JCI insight, Vol. 3, No. 18, 20.09.2018.

Research output: Contribution to journalArticle

Terilli Veenhuis, Rebecca ; Kwaa, Abena K. ; Garliss, Caroline C. ; Latanich, Rachel ; Salgado, Maria ; Pohlmeyer, Christopher W. ; Nobles, Christopher L. ; Gregg, John ; Scully, Eileen ; Bailey, Justin ; Bushman, Frederic D. ; Blankson, Joel N. / Long-term remission despite clonal expansion of replication-competent HIV-1 isolates. In: JCI insight. 2018 ; Vol. 3, No. 18.
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