Early Initiation of Antiretroviral Therapy Can Functionally Control Productive HIV-1 Infection in Humanized-BLT Mice

J Acquir Immune Defic Syndr. 2015 Aug 15;69(5):519-27. doi: 10.1097/QAI.0000000000000687.


Background: Recent reports showed that functional control of HIV-1 infection for a prolonged time is possible by early antiretroviral therapy (ART); however, its underlying mechanism needs to be studied with a suitable animal model. Recently, humanized-BLT (bone marrow, liver, and thymus) mouse (hu-BLT) was shown to be an excellent model for studying HIV-1 infection. We thus tested the feasibility of studying functional control of HIV-1 infection using hu-BLT mice.

Methods: Animals in 3 treatment groups (Rx-6h, Rx-24h, and Rx-48h) and untreated group were infected with HIV-1, followed by ART initiation at 6, 24, or 48 hours postinfection and continued daily for 2 weeks. Three weeks after stopping ART, CD8 T cells were depleted from all animals. Plasma viral load was monitored weekly using droplet digital polymerase chain reaction. Percentage of CD4 and CD8 T cells were measured by flow cytometry. In situ hybridization and droplet digital polymerase chain reaction were used to detect viral RNA (vRNA) and DNA.

Results: Although control animals had high viremia throughout the study, all Rx-6h animals had undetectable plasma viral load after ART cessation. After CD8 T-cell depletion, viremia increased and CD4 T cells decreased in all animals except the Rx-6h group. Viral DNA was detected in spleens of all animals and a few vRNA cells were detected by in situ hybridization in 1 of 3 Rx-6h animals.

Conclusions: Early ART did not act as prophylaxes but, rather, can control HIV-1 productive infection and prevented CD4 T-cell depletion in hu-BLT mice. This mouse model can be used to elucidate the mechanism for functional control of HIV-1.

Publication types

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

MeSH terms

  • Adenine / administration & dosage
  • Adenine / analogs & derivatives*
  • Adenine / therapeutic use
  • Animals
  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / therapeutic use*
  • Antigens, CD34
  • Bone Marrow
  • CD8-Positive T-Lymphocytes / immunology
  • DNA, Viral / isolation & purification
  • DNA, Viral / metabolism
  • Disease Models, Animal
  • Disease Progression
  • Gene Dosage
  • HIV Infections / drug therapy*
  • HIV-1 / genetics
  • HIV-1 / physiology*
  • Humans
  • Liver
  • Mice
  • Mice, Inbred NOD
  • Mice, Transgenic
  • Organophosphonates / administration & dosage
  • Organophosphonates / therapeutic use*
  • Pilot Projects
  • RNA, Viral / metabolism
  • Spleen / virology
  • Tenofovir
  • Thymus Gland
  • Viral Load
  • Virus Replication / drug effects


  • Anti-HIV Agents
  • Antigens, CD34
  • DNA, Viral
  • Organophosphonates
  • RNA, Viral
  • Tenofovir
  • Adenine