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

Qingsheng Li, For Yue Tso, Guobin Kang, Wuxun Lu, Yue Li, Wenjin Fan, Zhe Yuan, Christopher J. Destache, Charles Wood

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)519-527
Number of pages9
JournalJournal of Acquired Immune Deficiency Syndromes
Volume69
Issue number5
DOIs
StatePublished - Aug 15 2015

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HIV Infections
HIV-1
T-Lymphocytes
Viremia
Viral DNA
Viral RNA
Secondary Prevention
Viral Load
Therapeutics
In Situ Hybridization
Polymerase Chain Reaction
Thymus Gland
Flow Cytometry
Spleen
Animal Models
Bone Marrow
Liver
Infection

All Science Journal Classification (ASJC) codes

  • Infectious Diseases
  • Pharmacology (medical)
  • Medicine(all)

Cite this

Early Initiation of Antiretroviral Therapy Can Functionally Control Productive HIV-1 Infection in Humanized-BLT Mice. / Li, Qingsheng; Tso, For Yue; Kang, Guobin; Lu, Wuxun; Li, Yue; Fan, Wenjin; Yuan, Zhe; Destache, Christopher J.; Wood, Charles.

In: Journal of Acquired Immune Deficiency Syndromes, Vol. 69, No. 5, 15.08.2015, p. 519-527.

Research output: Contribution to journalArticle

Li, Qingsheng ; Tso, For Yue ; Kang, Guobin ; Lu, Wuxun ; Li, Yue ; Fan, Wenjin ; Yuan, Zhe ; Destache, Christopher J. ; Wood, Charles. / Early Initiation of Antiretroviral Therapy Can Functionally Control Productive HIV-1 Infection in Humanized-BLT Mice. In: Journal of Acquired Immune Deficiency Syndromes. 2015 ; Vol. 69, No. 5. pp. 519-527.
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AU - Tso, For Yue

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AU - Li, Yue

AU - Fan, Wenjin

AU - Yuan, Zhe

AU - Destache, Christopher J.

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