title: Early Initiation of Antiretroviral Therapy Can Functionally Control Productive HIV-1 Infection in Humanized-BLT Mice.
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.
authors.affiliation: *Nebraska Center for Virology and the School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE; and †Department of Pharmacy Practice, School of Pharmacy and Health Professions, Creighton University, Omaha, NE (Yue Li is now with College of Life Sciences, Nankai University, Tianjin, China).
authors.forename: Qingsheng
authors.initials: Q
authors.lastname: Li
authors.forename: For Yue
authors.initials: FY
authors.lastname: Tso
authors.forename: Guobin
authors.initials: G
authors.lastname: Kang
authors.forename: Wuxun
authors.initials: W
authors.lastname: Lu
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
authors.forename: Wenjin
authors.initials: W
authors.lastname: Fan
authors.forename: Zhe
authors.initials: Z
authors.lastname: Yuan
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Destache
authors.forename: Charles
authors.initials: C
authors.lastname: Wood
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018952:Antigens, CD34; D001853:Bone Marrow; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004279:DNA, Viral / Q000302:isolation & purification / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D018628:Gene Dosage; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008099:Liver; D051379:Mice; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D063065:Organophosphonates / Q000008:administration & dosage / Q000627:therapeutic use*; D010865:Pilot Projects; D012367:RNA, Viral / Q000378:metabolism; D013154:Spleen / Q000821:virology; D000068698:Tenofovir; D013950:Thymus Gland; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D018952:Antigens, CD34; D004279:DNA, Viral; D063065:Organophosphonates; D012367:RNA, Viral; D000068698:Tenofovir; D000225:Adenine