Microbicides

Research Grid

Microbicide Research	Description	Status
ANTIRETROVIRALS: TENOFOVIR (TFV) GEL - CONRAD and the International Partnership for Microbicides (IPM) have a co-exclusive license from Gilead for the development of 1% TFV gel as a microbicide.	TFV is a nucleotide reverse transcriptase inhibitor (NRTI) that prevents viral replication in susceptible cells. CONRAD investigators and partners completed clinical trials studying the safety and pharmacokinetics (PK) of TFV 1% gel in women and tolerance in men. TFV 1% gel is being tested for expanded safety and microbicidal efficacy in clinical studies.	Pharmacokinetic studies demonstrated that TFV levels in the vagina remained high for 24 hours following gel usage. CONRAD has supplied TFV 1% gel for a number of clinical trials, including CAPRISA 004, which showed TFV 1% gel to be 39% effective in reducing a woman’s risk of becoming infected with HIV during sexual intercourse. CONRAD also supplies TFV 1% gel for a number of Microbicide Trials Network (MTN) studies, including MTN-003, the Vaginal and Oral Interventions to Control the Epidemic (VOICE) trial, which was designed to compare daily oral TFV, daily oral TFV/emtricitabine (FTC) and TFV 1% gel for the prevention of HIV. Interim VOICE results showed daily use of oral TFV and TFV 1% gel to be ineffective in preventing HIV. CONRAD is providing TFV 1% gel for the FACTS 001 clinical trial, an effectiveness trial that is enrolling at least 2,200 women in South Africa who will use the gel in the BAT24 regimen.
PRECLINICAL EVALUATION: New and improved models to assess microbicide safety and efficacy are being developed.	An improved rabbit vaginal irritation (RVI) model that provides information on the proinflammatory potential of microbicide candidates has been developed. In combination with in vitro tests, this model will enhance the predictive power of preclinical evaluations. Models to assess microbicide efficacy are also being developed. New markers of mucosal inflammation have been identified and assessed in preclinical studies.	The improved RVI is being used to evaluate microbicide candidates that failed in Phase III clinical trials and candidates currently in development. Progress has been made toward establishing small animal models that are susceptible to HIV vaginal infection which will be useful for the early evaluation of microbicide efficacy. Low-dose, multiple-challenge R5/X4 SHIV and high-dose RT-SHIV vaginal infection models in monkeys have been developed to assess efficacy of advanced microbicide candidates. The newly identified markers of mucosal inflammation are currently being validated in clinical trials.
PRODUCT DEVELOPMENT: CONRAD’s product development scientists formulate the most promising microbicide candidates, either alone or in combination.	TFV is being incorporated into a variety of formulations (i.e., gels, intravaginal rings, and fast-dissolve tablets).	TFV was successfully formulated into a single entity gel. CONRAD’s product development team has formulated TFV in an intravaginal ring that can release the desired amount of TFV each day for a period of 90 days. Fast-dissolve vaginal tablets of TFV alone and TFV plus emtricitabine (FTC) (the drug combination in the HIV treatment known as Truvada) are in the final stages of development.

Microbicide Research

Description

Status

ANTIRETROVIRALS: TENOFOVIR (TFV) GEL - CONRAD and the International Partnership for Microbicides (IPM) have a co-exclusive license from Gilead for the development of 1% TFV gel as a microbicide.

TFV is a nucleotide reverse transcriptase inhibitor (NRTI) that prevents viral replication in susceptible cells. CONRAD investigators and partners completed clinical trials studying the safety and pharmacokinetics (PK) of TFV 1% gel in women and tolerance in men. TFV 1% gel is being tested for expanded safety and microbicidal efficacy in clinical studies.

Pharmacokinetic studies demonstrated that TFV levels in the vagina remained high for 24 hours following gel usage. CONRAD has supplied TFV 1% gel for a number of clinical trials, including CAPRISA 004, which showed TFV 1% gel to be 39% effective in reducing a woman’s risk of becoming infected with HIV during sexual intercourse. CONRAD also supplies TFV 1% gel for a number of Microbicide Trials Network (MTN) studies, including MTN-003, the Vaginal and Oral Interventions to Control the Epidemic (VOICE) trial, which was designed to compare daily oral TFV, daily oral TFV/emtricitabine (FTC) and TFV 1% gel for the prevention of HIV. Interim VOICE results showed daily use of oral TFV and TFV 1% gel to be ineffective in preventing HIV. CONRAD is providing TFV 1% gel for the FACTS 001 clinical trial, an effectiveness trial that is enrolling at least 2,200 women in South Africa who will use the gel in the BAT24 regimen.

PRECLINICAL EVALUATION: New and improved models to assess microbicide safety and efficacy are being developed.

An improved rabbit vaginal irritation (RVI) model that provides information on the proinflammatory potential of microbicide candidates has been developed. In combination with in vitro tests, this model will enhance the predictive power of preclinical evaluations.

Models to assess microbicide efficacy are also being developed.

New markers of mucosal inflammation have been identified and assessed in preclinical studies.

The improved RVI is being used to evaluate microbicide candidates that failed in Phase III clinical trials and candidates currently in development.

Progress has been made toward establishing small animal models that are susceptible to HIV vaginal infection which will be useful for the early evaluation of microbicide efficacy. Low-dose, multiple-challenge R5/X4 SHIV and high-dose RT-SHIV vaginal infection models in monkeys have been developed to assess efficacy of advanced microbicide candidates.

The newly identified markers of mucosal inflammation are currently being validated in clinical trials.

PRODUCT DEVELOPMENT: CONRAD’s product development scientists formulate the most promising microbicide candidates, either alone or in combination.

TFV is being incorporated into a variety of formulations (i.e., gels, intravaginal rings, and fast-dissolve tablets).

TFV was successfully formulated into a single entity gel. CONRAD’s product development team has formulated TFV in an intravaginal ring that can release the desired amount of TFV each day for a period of 90 days. Fast-dissolve vaginal tablets of TFV alone and TFV plus emtricitabine (FTC) (the drug combination in the HIV treatment known as Truvada) are in the final stages of development.