Multiple vaginal exposures to low doses of R5 simian-human immunodeficiency virus: strategy to study HIV preclinical interventions in nonhuman primates.
A nonhuman-primate model of human immunodeficiency virus type 1 (HIV-1) infection that more closely emulates human heterosexual transmission by use of multiple exposures to low doses of virus is critical to better evaluate intervention strategies that include microbicides or vaccines. In this report, we describe such a system that uses female pig-tailed macaques exposed vaginally to a CCR5-using simian-human immunodeficiency virus (SHIV(SF162P3)) at weekly intervals. Results of dose-titration experiments indicated that 3 once-weekly exposures to 10 tissue culture infectious doses of SHIV(SF162P3) resulted in consistent transmission of virus and establishment of systemic infection. The efficacy of cellulose acetate phthalate (CAP) as a vaginal microbicide was evaluated by applying it to the vaginal vault of macaques (n = 4) 15 min before each weekly exposure to SHIV(SF162P3). One conclusion that can be drawn from the data derived from multiple exposures to virus is that CAP prevented infection in 12 of 13 possible chances for infection, over the course of 39 total exposures. Our findings provide a basis to refine monkey models for transmission of HIV-1, which may be relevant to preclinical evaluation for therapeutic interventions.
Otten
Ron A
RA
HIV/AIDS and Retrovirology Branch, Mailstop G-19, DASTLR, NCHSTP, CDC, 1600 Clifton Rd., Atlanta, GA 30333, USA. rxo1@cdc.gov
Adams
Debra R
DR
Kim
Caryn N
CN
Jackson
Eddie
E
Pullium
Jennifer K
JK
Lee
Kemba
K
Grohskopf
Lisa A
LA
Monsour
Michael
M
Butera
Sal
S
Folks
Thomas M
TM
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000503:physiopathology / Q000635:transmission*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D014621:Vagina / Q000821:virology*