Format

Send to

Choose Destination
Pharm Res. 2015 Nov;32(11):3768-81. doi: 10.1007/s11095-015-1738-7. Epub 2015 Jun 16.

Pharmacodynamic Activity of Dapivirine and Maraviroc Single Entity and Combination Topical Gels for HIV-1 Prevention.

Author information

1
University of Pittsburgh, 204 Craft Avenue, Pittsburgh, Pennsylvania, 15213, USA. cdezzutti@mwri.magee.edu.
2
Magee-Womens Research Institute, Pittsburgh, Pennsylvania, USA. cdezzutti@mwri.magee.edu.
3
Magee-Womens Research Institute, Pittsburgh, Pennsylvania, USA.
4
University of Pittsburgh, 204 Craft Avenue, Pittsburgh, Pennsylvania, 15213, USA.
5
Statistical Center for HIV/AIDS Research and Prevention, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
6
International Partnership for Microbicides, Silver Springs, Maryland, USA.

Abstract

PURPOSE:

Dapivirine (DPV), a non-nucleoside reverse transcriptase inhibitor, and maraviroc (MVC), a CCR5 antagonist, were formulated into aqueous gels designed to prevent mucosal HIV transmission.

METHODS:

0.05% DPV, 0.1% MVC, 0.05% DPV/0.1% MVC and placebo gels were evaluated for pH, viscosity, osmolality, and in vitro release. In vitro assays and mucosal tissues were used to evaluate anti-HIV activity. Viability (Lactobacilli only) and epithelial integrity in cell lines and mucosal tissues defined safety.

RESULTS:

The gels were acidic and viscous. DPV gel had an osmolality of 893 mOsm/kg while the other gels had an osmolality of <100 mOsm/kg. MVC release was similar from the single and combination gels (~5 μg/cm(2)/min(1/2)), while DPV release was 10-fold less from the single as compared to the combination gel (0.4331 μg/cm(2)/min(1/2)). Titrations of the gels showed 10-fold more drug was needed to protect ectocervical than colonic tissue. The combination gel showed ~10- and 100-fold improved activity as compared to DPV and MVC gel, respectively. All gels were safe.

CONCLUSIONS:

The DPV/MVC gel showed a benefit blocking HIV infection of mucosal tissue compared to the single entity gels. Combination products with drugs affecting unique steps in the viral replication cycle would be advantageous for HIV prevention.

KEYWORDS:

Antiretroviral drugs; Drug combinations; HIV prevention; Pre-exposure prophylaxis; Rectal microbicides

PMID:
26078001
PMCID:
PMC4600024
DOI:
10.1007/s11095-015-1738-7
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Springer Icon for PubMed Central
Loading ...
Support Center