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Drug Deliv Transl Res. 2017 Dec;7(6):840-858. doi: 10.1007/s13346-017-0389-0.

An intravaginal ring that releases three antiviral agents and a contraceptive blocks SHIV-RT infection, reduces HSV-2 shedding, and suppresses hormonal cycling in rhesus macaques.

Author information

1
Population Council, 1230 York Avenue, New York, NY, 10065, USA. nderby@popcouncil.org.
2
Population Council, 1230 York Avenue, New York, NY, 10065, USA.
3
Aaron Diamond AIDS Research Center, 455 First Avenue, 7th Floor, New York, NY, 10016, USA.
4
Tulane Primate Research Center, 18703 Three Rivers Road, Covington, LA, 70433-8915, USA.
5
AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, 21702-1201, USA.
6
Science Department, Borough of Manhattan Community College, The City University of New York, 199 Chambers Street, New York, NY, 10007, USA.

Abstract

Women globally need access to multipurpose prevention technologies (MPTs) that prevent human immunodeficiency virus (HIV), sexually transmitted infections that increase HIV acquisition/transmission risk, and unintended pregnancy. Seeking an MPT with activity against HIV, herpes simplex virus-2 (HSV-2), and human papillomavirus (HPV), we developed a prototype intravaginal ring (IVR), the MZCL IVR, which released the antiviral agents MIV-150, zinc acetate, and carrageenan (MZC for short) and the contraceptive levonorgestrel (LNG). Previously, we showed that an MZC gel has potent activity against immunodeficiency viruses, HSV-2, and HPV and that the MZCL (MZC with LNG) IVR releases all four components in macaques in vivo at levels associated with efficacy. Vaginal fluid from treated macaques has in vitro activity against HIV, HSV-2, and HPV. Herein, we assessed the ability of the MZCL IVR to protect macaques against repeated co-challenge with HSV-2 and SHIV-RT (simian immunodeficiency virus [SIV] containing the reverse transcriptase gene from HIV) and prevent hormonal cycling. We evaluated in vivo drug release in co-challenged macaques by measuring drug levels in blood and vaginal fluid and residual drug levels in used IVRs. The MZCL IVR significantly prevented SHIV-RT infection, reduced HSV-2 vaginal shedding, and prevented cycling. No non-nucleoside HIV reverse transcriptase inhibitor (NNRTI)-resistant SHIV was detected in macaques that became infected after continuous exposure to MZC from the IVR. Macaques wearing the MZCL IVR also had carrageenan levels in vaginal fluid expected to protect from HPV (extrapolated from mice) and LNG levels in blood associated with contraceptive efficacy. The MZCL IVR is a promising MPT candidate that warrants further development.

KEYWORDS:

Contraception; HIV; HPV; HSV-2; Intravaginal ring; Multipurpose prevention technology

PMID:
28600625
PMCID:
PMC5656733
DOI:
10.1007/s13346-017-0389-0
[Indexed for MEDLINE]
Free PMC Article

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