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

JCI Insight. 2018 Sep 20;3(18):e122795. doi: 10.1172/jci.insight.122795.


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.

Keywords: AIDS vaccine; AIDS/HIV; T cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • AIDS Vaccines
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / virology
  • CD8-Positive T-Lymphocytes / immunology
  • Epitopes / immunology
  • Epitopes, T-Lymphocyte / genetics
  • Epitopes, T-Lymphocyte / immunology
  • HIV Infections / immunology*
  • HIV Infections / therapy
  • HIV Infections / virology
  • HIV Long-Term Survivors*
  • HIV-1 / genetics*
  • HLA-B Antigens
  • Humans
  • Time Factors
  • Viral Load
  • Virus Replication*
  • gag Gene Products, Human Immunodeficiency Virus
  • nef Gene Products, Human Immunodeficiency Virus


  • AIDS Vaccines
  • Epitopes
  • Epitopes, T-Lymphocyte
  • HLA-B Antigens
  • HLA-B57 antigen
  • gag Gene Products, Human Immunodeficiency Virus
  • nef Gene Products, Human Immunodeficiency Virus
  • nef protein, Human immunodeficiency virus 1