Use of standardized SCID-hu Thy/Liv mouse model for preclinical efficacy testing of anti-human immunodeficiency virus type 1 compounds.
We have developed standardized procedures and practices for infection of SCID-hu Thy/Liv mice with human immunodeficiency virus type 1 for the prophylactic administration of antiviral compounds and for evaluation of the antiviral effect in vivo. Endpoint analyses included quantitation of viral load by intracellular p24 enzyme-linked immunosorbent assay, DNA PCR for the presence of proviral genomes, flow cytometry to measure the representation of CD4+ and CD8+ cells, and cocultivation for the isolation of virus. Efficacy tests in this model are demonstrated with the nucleoside analogs zidovudine and dideoxyinosine and with the nonnucleoside reverse transcriptase inhibitor nevirapine. This small-animal model should be particularly useful in the preclinical prioritization of lead compounds within a common chemical class, in the evaluation of alternative in vivo dosing regimens, and in the determination of appropriate combination therapy in vivo.
Rabin
L
L
Preclinical Testing Group, SyStemix, Inc., Palo Alto, California, USA.
Hincenbergs
M
M
Moreno
M B
MB
Warren
S
S
Linquist
V
V
Datema
R
R
Charpiot
B
B
Seifert
J
J
Kaneshima
H
H
McCune
J M
JM
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D004279:DNA, Viral / Q000032:analysis; D016049:Didanosine / Q000627:therapeutic use; D004797:Enzyme-Linked Immunosorbent Assay; D016332:Fetal Tissue Transplantation; D005434:Flow Cytometry; D016655:HIV Core Protein p24 / Q000032:analysis; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D016031:Liver Transplantation / Q000502:physiology; D018655:Lymphocyte Count / Q000187:drug effects; D051379:Mice; D016513:Mice, SCID / Q000821:virology*; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D019829:Nevirapine; D016133:Polymerase Chain Reaction; D011725:Pyridines / Q000493:pharmacokinetics / Q000627:therapeutic use; D051381:Rats; D013601:T-Lymphocytes / Q000276:immunology; D013950:Thymus Gland / Q000637:transplantation; D014183:Transplantation, Heterologous; D015215:Zidovudine / Q000627:therapeutic use
D000998:Antiviral Agents; D004279:DNA, Viral; D016655:HIV Core Protein p24; D011725:Pyridines; D015215:Zidovudine; D019829:Nevirapine; D016049:Didanosine