New Science, New Hope: In Milestone for HIV Prevention, Proof of Concept Established for ARV Microbicide
Statement from Dr. Zeda Rosenberg, CEO, International Partnership for Microbicides
Contacts: Larry Miller, lmiller@ipmglobal.org, +1 301 608 4267
Leonard Solai, lsolai@ipmglobal.org, +27 (84) 660 6776
Holly Seltzer, hseltzer@ipmglobal.org, +1 301 608 4277
Dr. Zeda Rosenberg, CEO of the International Partnership for Microbicides (IPM), issued the following statement on the results of CAPRISA 004, an efficacy and safety trial of 1% Tenofovir Gel, an antiretroviral (ARV)-based vaginal microbicide being tested to prevent HIV infection in women:
Vienna, Austria, 19 July 2010 — Today, at the 18th International AIDS Conference in Vienna, Drs. Salim and Quarraisha Abdool Karim of the Centre for the AIDS Programme of Research in South Africa (CAPRISA), announced results from the first efficacy trial of an ARV-based microbicide. The trial, known as CAPRISA 004, was conducted in South Africa among 889 women to evaluate the ability of 1% tenofovir gel to prevent male to female HIV transmission. In an important milestone for HIV prevention, the CAPRISA 004 study found a 39% lower HIV infection rate in women using 1% tenofovir gel as compared to those women using a placebo gel. In addition, tenofovir gel was shown to be safe as tested.
These efficacy results are statistically significant and should be celebrated. For the first time, the HIV prevention research community has evidence that ARVs topically applied to the vaginal mucosa can offer protection against HIV and potentially other pathogens. The data generated by the CAPRISA 004 study represent “proof of concept” for a topical microbicide, making this a landmark in HIV prevention.
Tenofovir, developed by Gilead Sciences, Inc., is a well-established nucleotide reverse transcriptase inhibitor that interferes with the replication of HIV and is approved in tablet form for use in combination with other antiretrovirals to treat HIV.
CAPRISA 004 is the first clinical trial to study and demonstrate the efficacy of a next-generation microbicide designed to prevent women from acquiring HIV through sex with an infected male partner. These next-generation products are based on antiretroviral drugs similar to the ones currently being used to treat HIV/AIDS and to reduce mother-to-child transmission of the virus. ARVs as treatment have extended and saved millions of lives across the globe.
Over the course of the study, 38 of the women who used the tenofovir-containing gel acquired HIV, whereas 60 women who used a placebo gel became HIV-infected. No tenofovir-resistant virus was detected in the women who acquired HIV infection during the study.
In addition to showing efficacy against HIV, CAPRISA 004 found evidence that tenofovir gel also prevents transmission of herpes simplex virus type 2, or HSV-2. HSV-2 is a lifelong and incurable infection that can make those infected with the virus two-to-three times more likely to acquire HIV. Data collected during the CAPRISA 004 study indicate that tenofovir gel provided 51% protection against HSV-2.
CAPRISA 004 was a collaboration between CAPRISA, FHI, and CONRAD. It was funded by the United States Agency for International Development (USAID) and the South African Department of Science and Technology, with tenofovir provided by Gilead. IPM commends the hard work, dedication and efforts of the CAPRISA research team led by Drs. Karim, and especially the trial participants and their families.
This trial, designed and implemented by South African researchers and co-funded by the South African government, reflects the extraordinary contributions Africa is making to HIV prevention science.
In addition, we applaud Gilead Sciences for its leadership in the fight against HIV/AIDS. IPM and CONRAD have co-exclusive agreements with Gilead to develop tenofovir as a vaginal microbicide. The agreements, signed in 2006, allow tenofovir to be developed and manufactured as a microbicide in developing countries, and distributed at low or no cost to women. This agreement, and others like it with additional pharmaceutical partners, serves as a model of public-private partnership in fostering global health solutions. CONRAD has given the rights to manufacture tenofovir gel to the South African government, which will seek to ensure that if the product is licensed it can be manufactured and directly distributed in South Africa. Preparing for product access has been a cornerstone of the microbicide field.
Researchers can now begin to determine how best to build on the data generated from this proof-of-concept study. Regulatory authorities will need to determine if additional confirmatory trials will be required to support product licensure for 1% tenofovir gel as an HIV prevention tool. Contributing data may come from another important trial investigating different dosing strategies for tenofovir, the VOICE study – Vaginal and Oral Interventions to Control the Epidemic. The VOICE trial, funded by the US National Institutes of Health, is evaluating three different approaches for preventing transmission of HIV in women: once-daily 1% tenofovir vaginal gel, once-daily oral tenofovir tablets and a combination of oral tenofovir and emtricitabine, known commercially as Truvada®. Results are expected in 2013.
CAPRISA 004 is the 12th microbicide efficacy study and the first to demonstrate a significant reduction in HIV transmission. It is also the first study to test a vaginally applied ARV for efficacy. Historically it has taken decades – with more setbacks than advances – from the discovery of a pathogen until the licensing of a preventive drug or vaccine. Each trial builds on previous efforts, and when a trial has positive results, millions of people stand to benefit.
Multiple organizations have been working on the development of these highly potent next generation ARV-based microbicides, and this has been the focus of IPM’s work since inception. ARVs, like tenofovir, work in different ways by specifically targeting HIV, either by preventing it from entering a healthy human cell or from replicating once it is inside a cell. It is important for the greatest public health impact to have a robust pipeline of microbicide drug candidates from different classes of ARVs to advance into clinical trials. Examples of ARV-based microbicides in clinical trials include: tenofovir gel; dapivirine gel and ring; and UC-781 gel. Several other microbicide candidates belonging to different classes of ARVs are in preclinical development, including maraviroc, an FDA-approved therapeutic, which stops HIV from attaching to human cells.
It is possible that combinations of ARVs may increase the efficacy of future microbicide products, and the field is moving forward with several different promising combinations.
There is broad recognition of the importance of developing products that are easy to use and acceptable to women. Microbicide developers are researching ARV-based products in different formulations, informed by acceptability studies in Africa and elsewhere. These include gels that would be used daily or around the time of sex and long-acting vaginal rings that would be replaced once a month or even less often – to offer women more choices and longer protection, independently of sex. Researchers are also working to develop products that combine HIV-preventing microbicides with hormonal contraceptives to provide women with the greatest possible choices in reproductive health products.
Adapting ARVs to protect healthy adults from becoming infected with HIV has the potential to transform the global response to the HIV/AIDS epidemic. In addition to microbicides, other ARV- based prevention approaches in development include pre-exposure prophylaxis (PrEP) drugs, in the form of oral tablets or long-acting, novel formulations, as well as attempts to stem the tide of new infections by scaling up HIV treatment (treat-to-prevent).
The spread of the HIV/AIDS epidemic continues to outpace the world’s response to it. The findings from CAPRISA 004 are encouraging and a true cause for optimism. The need for new women-initiated tools for HIV prevention has never been more urgent.
The road ahead is likely to remain long and complex, but prevention strategies such as microbicides will revolutionize the world’s response to HIV. Research in this important area must continue as quickly as possible so that women and men throughout the world can have tools to safeguard their health and that of their families. IPM, inspired by the urgent need of people at risk and supported by the data from CAPRISA 004, is committed to turning hope into a scientific reality.
For more information about the CAPRISA 004 trial and its outcomes, visit the following websites: CAPRISA at: http://www.caprisa.org; CONTRAD at: http://www.conrad.org/; FHI at:http://www.fhi.org: Microbicides Trial Network at: http://www.mtnstopshiv.org; TIA at:http://www.lifelab.co.za/; and USAID at: http://www.usaid.gov.
About IPM: IPM is a nonprofit product development partnership dedicated to developing new HIV prevention technologies and making them available to women in developing countries. IPM has offices in the United States, South Africa and Belgium. Please visitwww.IPMglobal.org.