Advertisement

 

 

Prevention of vaginal and rectal HIV transmission by antiretroviral combinations in humanized mice.

Prevention of vaginal and rectal HIV transmission by antiretroviral combinations in humanized mice.
Author Information (click to view)

Gallay PA, Chatterji U, Kirchhoff A, Gandarilla A, Gunawardana M, Pyles RB, Marzinke MA, Moss JA, Baum MM,


Gallay PA, Chatterji U, Kirchhoff A, Gandarilla A, Gunawardana M, Pyles RB, Marzinke MA, Moss JA, Baum MM, (click to view)

Gallay PA, Chatterji U, Kirchhoff A, Gandarilla A, Gunawardana M, Pyles RB, Marzinke MA, Moss JA, Baum MM,

Advertisement
Share on FacebookTweet about this on TwitterShare on LinkedIn

PloS one 2017 09 0712(9) e0184303 doi 10.1371/journal.pone.0184303

Abstract

With more than 7,000 new HIV infections daily worldwide, there is an urgent need for non-vaccine biomedical prevention (nBP) strategies that are safe, effective, and acceptable. Clinical trials have demonstrated that pre-exposure prophylaxis (PrEP) with antiretrovirals (ARVs) can be effective at preventing HIV infection. In contrast, other trials using the same ARVs failed to show consistent efficacy. Topical (vaginal and rectal) dosing is a promising regimen for HIV PrEP as it leads to low systematic drug exposure. A series of titration studies were carried out in bone marrow/liver/thymus (BLT) mice aimed at determining the adequate drug concentrations applied vaginally or rectally that offer protection against rectal or vaginal HIV challenge. The dose-response relationship of these agents was measured and showed that topical tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) can offer 100% protection against rectal or vaginal HIV challenges. From the challenge data, EC50 values of 4.6 μM for TDF and 0.6 μM for FTC for HIV vaginal administration and 6.1 μM TDF and 0.18 μM for FTC for rectal administration were obtained. These findings suggest that the BLT mouse model is highly suitable for studying the dose-response relationship in single and combination ARV studies of vaginal or rectal HIV exposure. Application of this sensitive HIV infection model to more complex binary and ternary ARV combinations, particularly where agents have different mechanisms of action, should allow selection of optimal ARV combinations to be advanced into pre-clinical and clinical development as nBP products.

Submit a Comment

Your email address will not be published. Required fields are marked *

5 + seventeen =

[ HIDE/SHOW ]