Early initiation of antiretroviral therapy can functionally control productive HIV-1 infection in humanized-BLT mice

Authors

Qingsheng Li, University of Nebraska-LincolnFollow
For Yue Tso, University of Nebraska-LincolnFollow
Guobin Kang, University of Nebraska–LincolnFollow
Wuxun Lu, University of Nebraska-Lincoln
Yue Li, University of Nebraska-Lincoln
Wenjin Fan, University of Nebraska-LincolnFollow
Zhe Yuan, University of Nebraska-LincolnFollow
Christopher J. Destache, Creighton UniversityFollow
Charles Wood, University of Nebraska-LincolnFollow

Document Type

Article

Date of this Version

2015

Citation

J Acquir Immune Defic Syndr. 2015 August 15; 69(5): 519–527.

Comments

Copyright 2015 Wolters Kluwer. Used by permission.

Abstract

Background—Recent reports showed that functional control of HIV-1 infection for a prolonged time is possible by early anti-retroviral 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 three treatment groups (Rx-6h, Rx-24h, Rx-48h) and untreated group were infected with HIV-1, followed by ART initiation at 6, 24 or 48 hours post-infection and continued daily for two weeks. Three weeks after stopping ART, CD8+ T-cells were depleted from all animals. Plasma viral load (PVL) was monitored weekly using droplet digital PCR (ddPCR). Percentage of CD4⁺ and CD8⁺ T-cells were measured by flow cytometry. In situ hybridization (ISH) and ddPCR were used to detect viral RNA (vRNA) and DNA.

Results—While control animals had high viremia throughout the study, all Rx-6h animals had undetectable PVL after ART cessation. After CD8⁺ T-cells 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 ISH in one of three Rx-6h animals.

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