PrEP: A Possible Approval Like No Other

Via Poz, by Tim Horn

The AIDS Healthcare Foundation began a paid advertisement campaign urging Gilead Sciences to refrain from seeking approval from the U.S. Food and Drug Administration for Truvada for use of the combination tablet as HIV prevention, in an approach known as pre-exposure prophylaxis, or PrEP.

The ads were met by an outcry from the community. One prominent organization, the HIV Prevention Justice Alliance, issued a sign-on letter , dated March 16, urging the FDA "to examine the study results of PrEP rather than playing to speculation and fear."

While I agree that PrEP should be considered as an option in the HIV prevention toolkit and would ultimately support an effort by Gilead to expand Truvada's labeling to include PrEP--should the company petition the FDA for approval--I am also of the mind that a green light from the FDA should not be met with the rush-to-treatment that typically follows approval of a drug.

Given how little we know about the safe application of PrEP in a real-world setting--read: outside of a clinical trial--not to mention the expense of a comprehensive prevention program that includes PrEP, I think more feasibility studies need to take place before we consider a widespread HIV prevention program involving PrEP.

Here's what we do know: PrEP is effective in one population of at-risk individuals: men who have sex with men (MSM). The iPrEx clinical trial, sponsored by the National Institute of Allergy and Infection Diseases (NIAID) of the U.S. National Institutes of Health (NIH) and co-funded by the Bill & Melinda Gates Foundation, involved a large sample size (approximately 2,500) of MSMs. The study, which had sound design and statistical analysis, proved Truvada use resulted in significantly fewer infections compared with those using a placebo.

Read the rest

[If an item is not written by an IRMA member, it should not be construed that IRMA has taken a position on the article's content, whether in support or in opposition.]

Restructuring the NIAID HIV/AIDS Clinical Trials Networks

From the National Institute of Allergy and Infectious Diseases

The National Institute of Allergy and Infectious Disease (NIAID) is currently planning for the future of NIAID's HIV/AIDS clinical trial networks.

The following links connect to background information discussing the process, scientific priorities, structural components and collaborative opportunities with respect to the restructuring:

Restructuring NIAID's HIV/AIDS Clinical Trials Networks
Future Priorities for NIAID's HIV Prevention Research
Looking Ahead: NIAID's Future HIV/AIDS Therapeutics Priorities
Future Directions for NIAID's HIV Vaccine Clinical Research

Visit the NIAID website for links to staff presentations to the AIDS Research Advisory Committee (ARAC) about the network restructuring and public commentary from the ARAC meeting.

NIAID will also be hosting a public town hall meeting on Tuesday, October 26, 2010 at the Crystal Gateway Marriott in Arlington, VA. For details visit HIAID HIV/AIDS Clinical Trials Networks Town Hall Meeting.

Visit the NIAID Health and Research web page

Fauci Validates Need for RECTAL Microbicides

Statement of Anthony S. Fauci, M.D. Director, National Institute of Allergy and Infectious Diseases National Institutes of Health on National Black HIV/AIDS Awareness and Information Day February 7, 2009

Excerpt:

"Treatment is no substitute for prevention, however. NIAID-funded investigators are working to develop and validate new methods to protect against HIV infection, including microbicides that could be applied vaginally or rectally before sex; antiretroviral drug regimens that could be used to prevent infection in people who are at high risk of becoming infected with HIV; and, of course, vaccines to prevent HIV infection."

Read his whole statement here.

PS - IRMA loves you!

Protecting Women from HIV--Docs Hopeful About Microbicides

It is a real shame that this Scientific American article, posted today, ignores rectal microbicides and the prevention needs of gay men and other men who have sex with men. I urge IRMA members to read the item and post a comment (as I did), advocating for accuracy and inclusion when we discuss the important research happening around both vaginal AND rectal microbicides for both women AND men. And you may want to remind folks that unprotected anal intercourse is a common HUMAN behvior - and much more efficient at transmitting HIV compared to unprotected vaginal intercourse.
- Jim Pickett, IRMA Chair

Despite disappointing study results, scientists haven't given up on creating an effective way for women to protect themselves against HIV

By Rebecca Vesely - Scientific American

Antiretroviral (ARV) drugs have transformed HIV infection from a death sentence to a manageable chronic illness for millions worldwide. Now, scientists are testing whether ARVs can be used as microbicides, taken orally or applied vaginally as a gel or foam to prevent the transmission of the AIDS-causing human immunodeficiency virus.

If ARVs are proved as effective as microbicides, they have the potential to dramatically curb HIV infection rates. This is especially true in sub-Saharan Africa where women, who comprise nearly 61 percent of the adults living with HIV there, are eager for products besides condoms that they can use to protect themselves against the disease.

"I think it is very exciting to be integrating microbicides with drugs that have proven to work for treatment," says Roberta Black, chief of the Microbicide Research Branch at the National Institute for Allergy and Infectious Disease (NIAID) in Bethesda, Md. "This really jump-starts research efforts."

Microbicide research is at a crossroads as scientists begin testing the next generation of these drugs in the wake of a series of high-profile failures, including three late-stage clinical trials that were halted in the past year because the tested drug was found to be ineffective and, in one case, actually raised the risk of HIV transmission.

Read the rest.

The Future of Rectal Microbicides - an IRMA Q&A with Dr. Jim Turpin

Each step is part of the waft and weave leading to a safe, acceptable and effective rectal microbicide.

IRMA asks Jim Turpin, Ph.D., Microbicide Research Branch*, about the National Institutes of Health and its commitment to rectal microbicides


IRMA: Why are rectal microbicides an important part of the NIAID/NIH prevention portfolio?

Dr. Turpin: Rectal microbicides are important for a number of reasons They can play a role in reducing the number of MSM infections in the overall pandemic within the US and other countries. Recently updated figures from the CDC on men who have sex with men (MSM) in the US show that a large proportion of new infections are originating from the MSM community. Additionally, the practice of receptive anal intercourse (RAI) is not confined to MSM and is practiced in heterosexual cohorts. Depending upon the population, the incidence of at least one act of RAI per year can reach 30%. Furthermore, it has been proposed that any licensed vaginal microbicide has a high probability of being used off-label for RAI, which has resulted in the FDA considering the need for rectal microbicide safety studies as a requirement for licensure of a vaginal microbicide. All of these issues make the discovery, development and clinical testing of rectal microbicides a critical and integral part of the NIAID/NIH/DAIDS prevention and microbicide portfolio.

How is the science progressing?

We have seen significant progress in the understanding of how a potential rectal microbicide might be developed and deployed over the last few years. The Microbicide Development Program (MDP), under the Integrated Preclinical Clinical Program for HIV Topical Microbicides (IPCP-HTM) awarded to Peter Anton at UCLA and Ian McGowan at University of Pittsburgh, has been the main driver for rectal microbicide development in the DAIDS portfolio. The MDP has been instrumental in developing novel approaches to assessing the social and behavioral aspects of RAI and potential microbicide acceptability among men and women, adapting and creating new assays to assist in the discovery and study of rectal microbicide candidates, development of rectal specific formulations, and performing the first assessment of a vaginally formulated microbicide for safety in men and women when used rectally. We also have other grants that are contributing to the science aimed at developing new models and testing potential candidates, as well as a planned rectal microbicide safety study of 1% tenofovir gel to be performed by the DAIDS Microbicide Trials Network.

What are some of the key scientific challenges?

There are numerous challenges to development of a microbicide that is safe, acceptable and efficacious. We are currently at the stage where we still have more questions than answers. At the heart of the effort to develop a rectal microbicide are the nuts and bolts of any microbicide development effort; how do we achieve not only efficacy, but also safety and acceptability? We are addressing these scientific challenges by supporting the development of assays and models to select the best candidate microbicides for development, determining the optimal formulation for delivery of the microbicide, while maintaining its acceptability, identifying the right assays to perform to identify potential safety and toxicity issues of candidates during preclinical and clinical testing, and finally by performing the clinical trials needed to move a rectal microbicide product to licensure. But what must be remembered is that research into the discovery, testing and understanding of the potential impact of vaginally and rectally formulated microbicides on the gastrointestinal tract is still early in its development.

When did the field start to shift beyond simple safety studies of vaginal products and begin to consider efficacy of rectal-specific products?

I would say that the microbicide field has always recognized the need for rectal specific microbicides, and I would characterize any perceived shift to natural progression of our knowledge base as we have learned more about vaginal and rectal microbicides. Development of vaginal or rectal microbicides is an iterative process, as we must perform many types of preclinical and clinical studies all of which build on previous studies to move toward the ultimate goal of providing a safe, acceptable and efficacious microbicide. Thus, the perceived increased interest in designing rectal specific products is built upon the knowledge we have gained studying vaginal microbicides in the vaginal and rectal compartment and arises not as a shift but as the next logical step built upon previous studies.

What kinds of projects are underway?

One example is the Peter Anton’s IPCP-HTM. This award has been one of the main drivers for the rectal microbicide field in the DAIDS microbicide portfolio. Peter and his co-investigators have integrated basic assay development, acceptability, formulation and early clinical testing into a program which has significantly advanced the rectal microbicide field. There are also a number of other investigators working under the IPCP-HTM and the Microbicide Innovation Program awards that are either developing and/or testing potential rectal microbicides and/or developing new approaches and models that will directly impact the development of rectal microbicides in the future.

How can the community be involved in rectal microbicide research?

The community, and in particular those within IRMA, can be involved in several ways. The first and foremost is promoting an understanding of how HIV is transmitted and how to prevent themselves and their friends and family from becoming infected. The second is to realize that microbicide research, whether it is for a vaginal or rectal microbicide, will be an endeavor that will take time. As we have seen with the recent vaginal microbicide efficacy trials, there will be disappointments, failures and unexpected outcomes along the way. This is part of the scientific process. However, we must remember that each step is part of the waft and weave leading to a safe, acceptable and effective rectal microbicide. Finally, individuals can participate as volunteers in microbicide clinical trials. We are trying to interdict in a complex physiological and disease process that after 25 years of intensive research scientists still has many mysteries, and in order to realize a vaginal or rectal microbicide, we need to keep our focus on the prize.

What can we expect in the future?

There will be continued commitment of the NIAID DAIDS Prevention Sciences Program to the development and deployment of a safe, acceptable and effective rectal microbicide, through support of investigator initiated research. Specifically in the field of rectal microbicides, we expect to see the development of rectal-specific formulations for microbicides, as well as a movement toward creating rectal microbicide with more than one activity ingredient (combination microbicides). Complimentary to these efforts, we should begin to see increased behavioral and social science efforts to identify the proper use and context for rectal microbicides, as well as optimal applicators for their delivery. Finally, in the next few years, we should begin to see increased clinical safety testing of rectal microbicide candidates. Ultimately, I think you will see the beginnings of the integration of rectal microbicide with other prevention strategies such as pre-exposure prophylaxis (PrEP).

*Prevention Sciences Program, Division of AIDS, NIAID
National Institutes of Health, U.S. Department of Health and Human Services