Hidden

AN INTRAVAGINAL RING FOR  HIV PROPHLAXIS

 

Along with the provision of safe drinking water and the prevention of unnecessary death from malaria and tuberculosis, the search for a safe and effective HIV microbicide is one of the major programs in World Health.

The CAPRISA 004 and iPrEX trials using antiretroviral drugs (ARVs) are the only microbicide programs to have to demonstrated efficacy in preventing HIV transmission in clinical trials. Many ARVs are being investigated as potential microbicides, and there is growing consensus that, analogous to highly active antiretroviral therapy (HAART) for HIV treatment, a combination of ARVs is likely to be essential for a truly effective microbicide product. We have chosen a lead intravaginal ring (IVR) formulation consisting of tenofovir disoproxil fumarate (TDF) combined with emtricitabine (FTC) and the entry inhibitor maraviroc (MVC). This combination was chosen as a lead because: 1) the drugs are synergistic; 2) all three FDA approved agents are actively being investigated by the microbicide community and 3) Gilead and ViiV, their manufacturers, actively support the use of these ARVs as microbicides. The rationale for the choice of TDF and FTC is very strong as these are currently the only drugs to have demonstrated efficacy in clinical studies of HIV transmission. MVC, which has shown protection against SHIV transmission in macaques, is a rational addition.

IN VIVO RELEASE DATA IN MACAQUES

 

 

FIRST-IN-HUMAN TRIAL FOR HIV PROPHYLAXIS: VERSARING™ TRUVADA (TDF-FTC)

We are currently performing a clinical trial to test the safety and PK of three antiretroviral drug combinations (TDF, TDF-FTC and TDF-FTC-MVC) for the prophylaxis of HIV.

The TDF and TDF-FTC studies have been completed and show no significant safety concerns.

The IVRs were acceptable to all the six women in the trial.

The bioanalysis is in-progress.

IN VITRO AND IN VIVO DAILY RELEASE RATES AND IN VITRO-IN VIVO CORRELATION (IVIVC)

 

Drug

(IVR formulation)

In vitro release rate

(mg day-1)

In vivo release rate

(mg day-1)

 

IVIVC

 

TDF (TDF-FTC)

 

3.41 ± 0.33

 

0.68 ± 0.26

 

0.20

 

FTC (TDF-FTC)

 

3.39 ± 0.84

 

2.50 ± 0.58

 

0.74

 

TDF (TDF-FTC-MVC)

1.59 ± 0.29

 

0.75 ± 0.30

 

0.47

 

FTC (TDF-FTC-MVC)

2.84 ± 0.17

 

1.05 ± 0.32

 

0.37

 

MVC (TDF-FTC-MVC)

 

1.31 ± 0.17

 

0.86 ± 0.07

 

0.66