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J Antimicrob Chemother. 2016 Nov;71(11):3185-3194. Epub 2016 Aug 1.

HIV pre-exposure prophylaxis for women and infants prevents vaginal and oral HIV transmission in a preclinical model of HIV infection.

Author information

1
Division of Infectious Diseases, Center for AIDS Research, University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, NC, USA.
2
Division of Infectious Diseases, Center for AIDS Research, University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, NC, USA awahl@med.unc.edu.

Abstract

BACKGROUND:

Approximately 1.5 million HIV-positive women become pregnant annually. Without treatment, up to 45% will transmit HIV to their infants, primarily through breastfeeding. These numbers highlight that HIV acquisition is a major health concern for women and children globally. They also emphasize the urgent need for novel approaches to prevent HIV acquisition that are safe, effective and convenient to use by women and children in places where they are most needed.

METHODS:

4'-Ethynyl-2-fluoro-2'-deoxyadenosine, a potent NRTI with low cytotoxicity, was administered orally to NOD/SCID/γc-/- mice and to bone marrow/liver/thymus (BLT) humanized mice, a preclinical model of HIV infection. HIV inhibitory activity in serum, cervicovaginal secretions and saliva was evaluated 4 h after administration. 4'-Ethynyl-2-fluoro-2'-deoxyadenosine's ability to prevent vaginal and oral HIV transmission was evaluated using highly relevant transmitted/founder viruses in BLT mice.

RESULTS:

Strong HIV inhibitory activity in serum, cervicovaginal secretions and saliva obtained from animals after a single oral dose of 4'-ethynyl-2-fluoro-2'-deoxyadenosine (10 mg/kg) demonstrated efficient drug penetration into relevant mucosal sites. A single daily oral dose of 4'-ethynyl-2-fluoro-2'-deoxyadenosine resulted in efficient prevention of vaginal and oral HIV transmission after multiple high-dose exposures to transmitted/founder viruses in BLT humanized mice.

CONCLUSIONS:

Our data demonstrated that 4'-ethynyl-2-fluoro-2'-deoxyadenosine efficiently prevents both vaginal and oral HIV transmission. Together with 4'-ethynyl-2-fluoro-2'-deoxyadenosine's relatively low toxicity and high potency against drug-resistant HIV strains, these data support further clinical development of 4'-ethynyl-2-fluoro-2'-deoxyadenosine as a potential pre-exposure prophylaxis agent to prevent HIV transmission in women and their infants.

PMID:
27494916
PMCID:
PMC5079298
DOI:
10.1093/jac/dkw283
[Indexed for MEDLINE]
Free PMC Article

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