Tenofovir

Tenofovir, formulated as a vaginal gel, is the first ARV-based microbicide shown to help protect women against HIV during sex however, not all studies of tenofovir gel have confirmed these results and an additional study is ongoing to help researchers to further understand and confirm whether tenofovir gel can be used to prevent HIV in women.

Several studies have also shown the great potential of oral tenofovir however, further research and analysis is needed to determine whether oral tenofovir is a feasible HIV prevention option for women.

How does tenofovir work?

Tenofovir is a nucleotide reverse transcriptase inhibitor (NRTI) that works by stopping the virus from copying its genetic material once the virus enters a healthy cell.

What is tenofovir’s clinical history?

The safety and efficacy of tenofovir as an oral therapeutic has been well documented because the precursor to tenofovir, tenofovir disoproxil fumarate, has been studied since 1998 and is an approved treatment for HIV under the name Viread®.

In particular, two recent milestone clinical trials demonstrate tenofovir's effectiveness in preventing HIV in a variety of formulations:

CAPRISA 004: Results from the landmark Phase IIb clinical trial CAPRISA 004, announced in July 2010, established proof-of-concept for microbicides using tenofovir in a gel form. The study, conducted by the Centre for the AIDS Programme of Research In South Africa (CAPRISA), showed 1% tenofovir vaginal gel to be 39 percent effective at preventing sexual transmission of HIV to women during sex with an HIV-positive male partner. It was also shown to be 51 percent effective at preventing infection with herpes simplex virus type 2 (HSV2).

iPrEx: The December 2010 results from the iPrEx trial, a Phase III study, showed that a daily oral formulation of tenofovir taken once a day in conjunction with comprehensive HIV prevention services led to a 44 percent reduced risk of becoming infected with HIV-1 in the clinical trial population. This trial was conducted by U.S. National Institutes of Health with co-funding from the Bill & Melinda Gates Foundation and study medication donated by Gilead Sciences, Inc.

In 2006, Gilead granted both IPM and CONRAD rights to develop tenofovir as a topical microbicide for use by women in developing countries.   

How has IPM supported development of tenofovir?

In 2006, IPM and CONRAD obtained a nonexclusive, royalty-free agreement from Gilead to develop tenofovir as a topical microbicide for use by women in the developing world.

IPM support for the product has included preclinical studies and clinical safety and pharmacokinetic (PK) trials in collaboration with CONRAD (PK trials assess absorption, distribution, metabolism and excretion to establish that a drug reaches tissues and cells where it is needed to be effective).

IPM supported tenofovir production for the Microbicide Trial Network's (MTN) VOICE trial and for MTN 001 and its manufacturing group initiated an effort to identify potential manufacturers for future clinical studies and post-approval access to tenofovir.

How is tenofovir being tested in clinical trials outside of IPM? 

Tenofovir is being tested in a variety of formulations and clinical trials outside of IPM:

VOICE: Tenofovir is being tested in VOICE (Vaginal and Oral Interventions to Control the Epidemic), a Phase IIb efficacy and safety trial in nearly 5,000 women in South Africa, Uganda, Zambia and Zimbabwe.

VOICE is the first efficacy trial of both pre-exposure prophylaxis (PrEP) and vaginal prevention methods, including a once-daily microbicide.

The products being tested are tenofovir microbicide gel, tenofovir disoproxil fumarate (TDF), an oral form of tenofovir, and Truvada®, which is an approved HIV treatment that combines tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) in the same tablet.

Results are expected in 2013 and if the data support licensure, tenofovir gel could be the first microbicide available to women as early as 2013.

Partners in PrEP: In 2012, results are expected from the Partners in PrEP study, which is a Phase III trial evaluating the safety and efficacy of once-daily oral TDF and once-daily oral Truvada® among HIV serodiscordant couples in Kenya and Uganda.

FEM-PrEP: The FEM-PrEP study, a Phase III trial, is also evaluating the safety and effectiveness of once-daily oral Truvada® for HIV prevention in women. The trial is being carried out in Kenya, Malawi, South Africa, Tanzania and Zimbabwe. Results are expected in 2013.

What stage of development is tenofovir in at IPM and in what forms? Could it be combined with other ARV-based candidates?

A maraviroc-tenofovir combination film is currently in early preclinical evaluation at IPM. As noted above, tenofovir has also been developed by CONRAD as a vaginal gel but is not available for use yet.

Where can I get more information?

For a bibliography of scientific papers and articles on IPM-supported research on tenofovir, visit our Publications & Media page.