Distinct mechanisms of long-term virologic control in two HIV-infected individuals after treatment interruption of anti-retroviral therapy

Nat Med. 2021 Nov;27(11):1893-1898. doi: 10.1038/s41591-021-01503-6. Epub 2021 Oct 28.


Certain infected individuals suppress human immunodeficiency virus (HIV) in the absence of anti-retroviral therapy (ART). Elucidating the underlying mechanism(s) is of high interest. Here we present two contrasting case reports of HIV-infected individuals who controlled plasma viremia for extended periods after undergoing analytical treatment interruption (ATI). In Participant 04, who experienced viral blips and initiated undisclosed self-administration of suboptimal ART detected shortly before day 1,250, phylogenetic analyses of plasma HIV env sequences suggested continuous viral evolution and/or reactivation of pre-existing viral reservoirs over time. Antiviral CD8+ T cell activities were higher in Participant 04 than in Participant 30. In contrast, Participant 30 exhibited potent plasma-IgG-mediated neutralization activity against autologous virus that became ineffective when he experienced sudden plasma viral rebound 1,434 d after ATI due to HIV superinfection. Our data provide insight into distinct mechanisms of post-treatment interruption control and highlight the importance of frequent monitoring of undisclosed use of ART and superinfection during the ATI phase.

Publication types

  • Case Reports
  • Randomized Controlled Trial
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use*
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood*
  • CD4 Lymphocyte Count
  • CD8-Positive T-Lymphocytes / immunology*
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • HIV-1 / immunology*
  • Humans
  • Immunoglobulin G / blood
  • Male
  • Middle Aged
  • Patient Compliance*
  • Viral Load / immunology
  • Viremia / drug therapy
  • Viremia / immunology
  • Virus Activation / genetics
  • env Gene Products, Human Immunodeficiency Virus / blood
  • env Gene Products, Human Immunodeficiency Virus / genetics


  • Anti-HIV Agents
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Immunoglobulin G
  • env Gene Products, Human Immunodeficiency Virus