A single dose of a MIV-150/Zinc acetate gel provides 24 h of protection against vaginal simian human immunodeficiency virus reverse transcriptase infection, with more limited protection rectally 8-24 h after gel use.
Previously we showed that repeated vaginal application of a MIV-150/zinc acetate carrageenan (MIV-150/ZA/CG) gel and a zinc acetate carrageenan (ZA/CG) gel significantly protected macaques from vaginal simian human immunodeficiency virus reverse transcriptase (SHIV-RT) infection. Gels were applied either daily for 2 weeks or every other day for 4 weeks, and the animals were challenged 4-24 h later. Herein, we examined the effects of a single vaginal dose administered either before or after virus challenge. Encouraged by the vaginal protection seen with MIV-150/ZA/CG, we also tested it rectally. Vaginal applications of MIV-150/ZA/CG, ZA/CG, and CG gel were performed once 8-24 h before, 1 h after, or 24 h before and 1 h after vaginal challenge. Rectal applications of MIV-150/ZA/CG and CG gel were performed once 8 or 24 h before rectal challenge. While vaginal pre-challenge and pre/post-challenge application of MIV-150/ZA/CG gel offered significant protection (88%, p<0.002), post-challenge application alone did not significantly protect. ZA/CG gel reduced infection prechallenge, but not significantly, and the effect was completely lost post-challenge. Rectal application of MIV-150/ZA/CG gel afforded limited protection against rectal challenge when applied 8-24 h before challenge. Thus, MIV-150/ZA/CG gel is a highly effective vaginal microbicide that demonstrates 24 h of protection from vaginal infection and may demonstrate efficacy against rectal infection when given close to the time of HIV exposure.
Population Council , New York, New York, USA.
Jessica
J
Kenney
Rachel
R
Singer
Nina
N
Derby
Meropi
M
Aravantinou
Ciby J
CJ
Abraham
Radhika
R
Menon
Samantha
S
Seidor
Shimin
S
Zhang
Agegnehu
A
Gettie
James
J
Blanchard
Michael
M
Piatak
Jeffrey D
JD
Lifson
José A
JA
Fernández-Romero
Thomas M
TM
Zydowsky
Melissa
M
Robbiani
D000282:Administration, Intravaginal; D000285:Administration, Rectal; D000818:Animals; D000890:Anti-Infective Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D005260:Female; D006558:Herpes Genitalis / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control*; D018258:Herpesvirus 2, Human / Q000187:drug effects*; D006801:Humans; D011725:Pyridines / Q000493:pharmacokinetics / Q000494:pharmacology*; D012194:RNA-Directed DNA Polymerase / Q000187:drug effects*; D012007:Rectum / Q000473:pathology / Q000821:virology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000187:drug effects*; D013997:Time Factors; D016896:Treatment Outcome; D014508:Urea / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D014621:Vagina / Q000473:pathology / Q000821:virology; D014622:Vaginal Creams, Foams, and Jellies; D019345:Zinc Acetate / Q000493:pharmacokinetics / Q000494:pharmacology*
D000890:Anti-Infective Agents; C510296:MIV 150; D011725:Pyridines; D014622:Vaginal Creams, Foams, and Jellies; D014508:Urea; D012194:RNA-Directed DNA Polymerase; D019345:Zinc Acetate