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Future Priorities for NIAID’s HIV Prevention Research

NIAID

As we begin to discuss the restructuring of NIAID’s clinical trials networks, let us first focus on the Institute’s HIV prevention research agenda. Developing new biomedical tools that can safely and effectively prevent HIV acquisition and transmission is critical to addressing the global HIV/AIDS pandemic. Currently, we are exploring several promising HIV prevention strategies that, if proven successful, could have a significant impact on reducing the incidence of new infections. These strategies include microbicides — gels, foams, creams, and other formulations designed to prevent sexual transmission of HIV — and pre-exposure prophylaxis (PrEP), attempting to block HIV infection by providing antiretroviral medicines to people who are not infected with HIV but who are at high risk for infection. HIV vaccines are also a major focus of our prevention research efforts, but we will discuss that area specifically in an upcoming blog post.

Vaginally or rectally applied microbicides could potentially provide women and men with a means of protecting themselves against sexually transmitted HIV infection. Non-human primate studies have shown that antiretroviral-based microbicides protect against HIV infection, and these types of products are now being tested in people. Nearly a dozen clinical studies are currently evaluating different microbicide candidates and delivery methods, such as the VOICE trial, which is comparing oral antiretroviral medicines to an antiretroviral-based topical gel for HIV prevention. That study is being conducted by the NIAID-supported Microbicide Trials Network. Future microbicide research efforts will focus on evaluating new products, formulations and routes of administration with the goal of finding a safe and effective microbicide that is reliably used by its intended population.

Using antimicrobial drugs prophylactically has been shown to be effective in preventing other infectious diseases, such as malaria, and lends hope that a similar strategy using antiretroviral medicines could do the same for preventing HIV acquisition. The strategy also has been shown to block HIV transmission from infected mothers to their infants and currently is being explored further in the multinational clinical trial known as the PROMISE study. That trial, which is being conducted by the NIAID-supported International Maternal Pediatric Adolescent AIDS Clinical Trials network, is examining how antiretroviral regimens may best reduce the risk of HIV transmission from infected pregnant women to their babies during pregnancy and breastfeeding while preserving the health of the children and mothers.

In addition to the PROMISE study, several other studies are underway that are evaluating PrEP among different populations with some results expected later this year or early into 2011.

Moving forward in designing and evaluating microbicides and PrEP, questions related to adherence and behavior must be considered. These prevention tools will only be effective if they are used properly and consistently, and we need to be sure that benefits of the interventions are not obviated by increased risky behavior.

Given what I’ve noted here in this blog post about NIAID’s current HIV prevention research agenda and potential future directions, please consider the following:

  1. Have we considered the most important scientific priority areas for HIV prevention? If not, what are we missing?
  2. Among the priority areas that we have identified, what is the appropriate balance to pursue (e.g., should we devote the majority of our attention to one area in particular)?
  3. How will a “test and treat” research agenda be affected if it is discovered that expanded HIV testing and linkage to care and antiretroviral treatment provides both a clinical benefit to the individual infected with HIV and a reduction in HIV transmission to the larger population?
  4. Are there remaining research issues associated with preventing mother-to- child HIV transmission?
  5. What are the emerging opportunities in combination prevention? What threshold of reduced HIV incidence in animal models should be sufficient to initiate a clinical trial?
  6. What other HIV prevention-related questions should be considered as important scientific priorities?

In addition to microbicides and PrEP, there is a range of other possible approaches to preventing HIV acquisition and transmission that could be evaluated, including strategies designed to increase utilization of HIV testing, behavioral interventions aimed at reducing HIV risk, and approaches to reducing alcohol or drug use, which contribute to increased risk for HIV infection. Additionally, structural interventions – those focused on at-risk communities groups as compared to individuals – could be evaluated as well.

Integrating proven HIV prevention strategies is another important area of exploration. As the number of validated prevention approaches increases, we need to determine optimal combinations in terms of impact and cost-effectiveness. Given that we are unlikely to find a prevention strategy that is fully effective for everyone, a multi-pronged approach tailored to different communities is the best way to end the global HIV/AIDS pandemic. This will require strong partnerships with the Centers for Disease Control and Prevention (CDC), the President’s Emergency Plan for AIDS Relief, and other NIH institutes and centers. For example, NIAID and CDC are preparing to launch the HIV Prevention Trials Network (HPTN) 065 study, or TLC+, a feasibility study that will involve expanded HIV testing, better linking of those who test HIV positive to medical care and treatment, and improving adherence to HIV treatment.

I hope that you will give some thought to these questions and provide us with your feedback. In the next blog entry, I’ll discuss NIAID’s therapeutic research priorities.

Comments

  1. What barriers must be overcome if a PrEP strategy employing intravaginal/intrarectal administration of one or more broadly neutralizing antibody (2F5, 4E10, 2G12 etc) formulations might be clinically assessed? Is this just a manufacturing cost issue (as suggested by PMID: 18316741), or are there other obstacles?
    Thanks in advance

  2. After almost 30 years of simplified HIV Prevention (1. Don’t Do “It”; and, 2. If you really gotta do “it”, use one of these things), it’s time for a change in strategy. It is exceedingly clear that packaging these messages in a variety of different packages, has resulted in failure, especially in minority communities.
    Messages that celebrate intimacy, instead of barriers to intimacy, will be embraced by a weary population. Treatment as Prevention, PreP, expanded access to PEP, microbicides, needle exchange, circumcision, vaccines, risk reduction, health education are all positive approaches.
    I encourage expanded NIH research in these areas of new prevention technologies. Give those of us in the field something else to utilize in HIV Prevention, besides condoms, abstinence and outdated group interventions.

  3. What about the people whose body is fighting it off naturally? There are Long term NON- Progressors….and we never hear a word about them! What about, you can’t look at a person and see if they are sick, all the time. Healthy people have no visible signs of the virus! Healthy people can control the viral load by maintaining a regimen of health and well being. Cancer is a bigger threat, than HIV…and If you do drugs, and live on alcohol..smoke a pack of cigarettes a day….then , YES…you are killing yourself.
    If you own a race car….you put good gas, and the finest oil in it! We are more worried about our possessions and our pets , than we are our own health. EAT GOOD TO LIVE LONG! PERIOD!

  4. Michael E. Bailey says:

    The best chance for significantly reducing or eliminating HIV/AIDS spred would seem to be moving forward with research on both the new microbicides and new PrEp at the same time. Both seem to show real promise. The highest priority for continued research sould be to concentrate on funding the testing of medications in both the PrEP and microbicide categories on the ones that show the best results in early evaluations. Health IT will be able to help create better, more detailed, more accurate and accessible research studies and may help speed up the research and approval processes for the new medications. An increasing role for Health IT, could not onljy make a more accurate and faster research and approval process but also reduce the costs of the process. Health IT should not and cannot replace live animal and human research subjects.
    One area where few research subjects are recruited and where outreach on HIV/AIDS prevention and treatment lags behind is the disabled community. Persons with developmental disabilities, the blind and deaf, and dually diagnosed with developmental disabilities and mental health disabilities need greater access to prevention and treatment information but it needs to be presented to them in alternative formats. Some people with developmental disabilities are not able to read well and printed information in words would not benefit them much; but if the same information was presented in picture form, they could understand it. Some need a large print format. And some need internet access with websites that are card reader accessible. Best wishes, Michael E. Bailey.

  5. Omar Bagasra, MD, PhD says:

    This article asking lots of questions about various HIV prevention trials going on in Africa. I have two major concerns. Why we are not talking about circumcision that reduces HIV infection up to 99%? And, the two drugs that are being used as prevention cream are RT inhibitors that work after HIV entered its targets. Generally, in the vagina and anal areas after HIV enters the target cells these cells are mobile and reach to lymph nodes in minutes, essentially nullifying all the ARV drugs. We also have no data (to the best of my knowledge) if these ARVs have HIV preventive effects since they do not prevent HIV entry. It appears to be that these trials will benefit the drug makers more than the participants. I hope we are certain that these 5,000+ from Africa are not being used guinea pigs for the corporate drug trials.

  6. Seyed Mohsen Khatami says:

    Dr. Carl W.Diffenbach, Director of NIAID’s Division of AIDS in a post blog describes the future priorities for NIAID’s HIV prevention research. As he dreams according him: “Developing new biomedical tools that can safely and effectively prevent HIV acquisition and transmission is critical to addressing the global HIV/AIDS pandemic”.
    In another part of his statement he says the following:
    “These prevention tools will only be effective if they are used properly and consistently, and we need to be sure that benefits of the interventions are not obviated by increased risky behavior”.
    Dear Dr. Carl W.Diffenbach with all respect to you, as a scientist I am expecting a pragmatist attitudes and behaviors from you in this catastrophic situation and not an idealistic and naive one. Human community is suffering already a catastrophic HIV pandemic ranging as a minimum, according to WHO, from 33 million infected people. In this situation one must raise the preventive threshold more than you have postulated. We put forward the following threshold and I hope that you and your colleagues will agree with me:
    1-By changing the pattern of HIV infection via treatment of the collection HIV viruses, isolated form the plasma of already infected patients, by electroporation and potassium permanganate and returning the treated viruses intravenously to individual patients creating an opportunity for immune system to suppress the virus to the level of undetectable in the blood without to be needed HART and other preventive tools. We have presented the results of our trial to Dr. Margaret Chan, The Director-General of World Health Organization (WHO). I hope that this result will be also considered by you and your colleagues in NIH. In the case that you and your colleagues are interested for consideration we humbly declare our readiness to send the material for you.
    2-As the mutation is advantageous to HIV virus in order to avoid a robust response from immune system the mutation can also be disadvantageous to HIV virus. This possibility can be used for development of drugs in order to direct the pattern of mutation in a manner to create an opportunity for immune system to response robustly to HIV infection without to be needed irrational consumption and administration of HART medications and other preventive tools.
    3-The final solution is the elimination of HIV virus by vaccine. This solution can not be achieved other than to invest for designation of a single RNA-based super vaccine as a great infrastructure in the field of infectious disease for medical care in order to eliminate all infectious RNA viruses.
    I hope my humble comments will be posted in your blog in order to realize and discuses the problem of HIV in a wider perspective. I am sending this comment from my pour laboratory near central desert of Iran.
    Best regards,
    Seyed Mohsen Khatami

  7. True HIV prevention will put the power to stop HIV transmission in the hands of everyone. I would like to see an emphasis on Microbicide research that empowers receptive partners, in sexual intercourse both heterosexual and homosexual, to take control of safer sex practices. These would include Microbicide strategies to be used -at the time of sexual intercourse. Scientific priorities must include availability and access as key components of HIV prevention research.
    Whether anti-retroviral medication is given prior to infection or post-infection I believe it is a disservice to people most at risk for HIV infection to consider these medications as HIV prevention. It only takes an observation of the failure to distribute HIV/AIDS therapies worldwide to predict similar PrEP failures.
    I believe it is important to emphasize that HIV is ultimately shared through sex and needles. Where condom use has failed other microbicides must succeed. The scientific agenda must become aware and engage in the cultural and religous obstacles to HIV prevention worldwide. International faiths such as Catholicism, Islam and Judiasm must be partners in this scientific agenda or new HIV prevention strategies will suffer a similar fate as condom use.

  8. Richard Maskiewicz says:

    It may not be appropriate to arbitrarily separate and differentiate between “microbicide” and “PrEP”.
    Sustained duration microbicides would most certainly be considered prophylactic, and the earlier in the infection process a PrEP’s mechanism of action is involved, the more it behaves like a topical microbicide in terms of decreased probability of adverse systemic effects.

  9. Thank you for the chance to provide input. As chair of IRMA – International Rectal Microbicide Advocates – I appreciate the chance to share some of the goals and objectives we laid out in our new document “From Promise to Product – Advancing Rectal Microbicide Research and Advocacy.”
    The comprehensive document reports on the growing scientific activity in the rectal microbicide field, capturing the optimism among researchers and advocates alike as the field sets its sights on the development of safe and effective rectal-specific products that will provide protection against HIV during anal intercourse. Additionally, IRMA continues to call for a Global Rectal Microbicide Development plan by which stakeholders can coordinate efforts across the full range of scientific activities, developing strategies and setting priorities. Such a plan does not yet exist. An updated resource tracking of funds specifically allocated to rectal microbicide research and development — the only such exercise — is followed by a call for escalating funding over the next 10 years and for increased diversity in the funding portfolio as well.
    Below are the bullets. For more details, see section 5 of “From Promise to Product.”
    http://rectalmicrobicides.org/materials.php
    Increase activity in all areas of rectal microbicide research (basic, pre-clinical, clinical,s ocio-behavioural).
    Create a Global Rectal Microbicide Development Plan.
    Bring more researchers to the rectal microbicide field.
    Determine the safety of lubricants for rectal use.
    Frame the discussion of RMs and other HIV prevention options in the context of anal health.
    Recognise anal intercourse as a driver of the HIV pandemic—among gay men and other men who have sex with men (MSM), and between women and men.
    Address the burden of HIV among gay men and other MSM around the world.
    Thanks for your consideration.

  10. The post mentioned “a multi-pronged approach tailored to different communities is the best way to end the global HIV/AIDS pandemic.” What about the jail and prison system? Is anyone working on an approach tailored to that section of society or have we just given up?
    Prisoners are at a much higher risk for infection because of, among other, the association of injection drug use with incarceration. According to many studies HIV is five to six times more prevalent among people who are incarcerated.

  11. I think that everyone who test for HIV or any other STD’s should be tested for a CCR5 mutation and store in a data base so that when someone needs a bone marrow transplant can go to a data base of millions of people and see if a match of HIV resistant virus can be found, and then be given to that particular person that may need it, and thus avoid disease-grafting complications and ultimately be “cured” of HIV. I think we should have a data base here in the states and in every country in the world. The more people we have with a HIV resistance virus,the more chances we have to find a donor.We will have them in that data base instead of going out there and try to find them. Kind of like the Berlin patient. I just wanted to throw it out there.

  12. PREVENTION of mother-to-child-transmission of HIV….arguably the most successful prevention tool available today. We clearly know how to reduce MTCT in utero and intra-partum to 1-2% in resource rich settings and are working towards that goal in the rest of the world where access to ARVs and PMTCT services is challenging. We are also tackling transmission during breastfeeding through PROMISE as mentioned above. At this point, It would be easy to say ‘mission accomplished’.
    However, the reality is that there are still 1200 infants born with HIV EVERY DAY, necessitating more research on many fronts. Understanding how to bring these proven prevention methods to scale is an obvious area of research that has implications for every prevention modality from PMCTC to PrEP and microbicides. If we can’t reach the populations that need these prevention tools, the best prevention methods are useless. And while we may know how to reduce transmission to low levels with ARV, we still don’t really understand the basic science of mother-to-child transmission events. Critically, why is it that 60% of infants born to HIV+ women will remain uninfected despite no therapy whatsoever? Why can an infant be exposed to HIV in mother’s milk every day for up to 2 years and not get infected? If we knew the answers to these questions, we’d be that much closer to the ultimate prevention tool, an HIV vaccine.
    As the Clinical Trial Networks are restructured to address the global HIV pandemic, we must maintain a focus on the unanswered basic and implementation science questions that will reduce the number of infants born with HIV. The most efficient way to do this is by maintaining a network dedicated to HIV in women and children. This will also ensure that advances in other areas of research, in therapeutics and vaccines, will not leave women and children behind.
    Respectfully submitted,
    Jeffrey T. Safrit, PhD
    Director, Clinical & Basic Research
    Elizabeth Glaser Pediatric AIDS Foundation
    http://Www.pedaids.org

  13. Charlene Dezzutti says:

    The HIV prevention networks have been productive to date. Merging both prevention networks into one will likely result in unintended consequences.
    The HPTN has developed a successful niche in their TLC program and dealing with HIV and drug addition. The MTN has developed a successful niche in their microbicides and PrEP programs. Both groups are focusing on those populations who will likely benefit the most. The HPTN and MTN communicate between all levels of leadership. While both groups are dealing with HIV prevention, merging them will dilute their efforts and impede their success for several years due to dealing with the re-organization.
    I have experience with a similar situation in which several CDC Divisions and Centers were re-organized into a “Super Center”. I worked at the CDC for 13 years. During my last 5 years, there was a need to re-organize with the thought of merging efforts to centralize the information and work flows between programs. The opposite occurred. There was no transparency and the mandates that were made created confusion. With this re-organization, new layers of bureaucracy were created slowing the work and halting the interactions between Divisions. While the Super Centers are now being dismantled, the re-organization effects remain.
    With the immediate need to stop the spread of HIV and the shrinking dollar, it makes more sense for the programs that have been successful so far and will make the biggest impact on the epidemic to continue not encumbered by “re-organization”.

  14. Anne Davis says:

    I am concerned about the health of women in the United States, particularly as it has been disproportionately impacted by HIV. I wish to support the following areas discussed and prioritized by the HANC Legacy Project during a first-time-ever Consultation on HIV Research and Women on June 11th and 12th, 2010. Their review reflects key concerns such as sensitivity to culture, quality of life, and the changing needs of women across the lifespan.
    I respectfully ask that NIAID includes the following priorities related to HIV prevention and treatment for United States’ women:
    Epidemiological data must continue to drive research priorities. Awareness of the impact that HIV has had on women in the United States has been heightened through the use of epidemiological data from the Centers for Disease Control and Prevention. The CDC guidance mandates prioritizing HIV prevention efforts for those populations who are most burdened by infection.
    HIV treatment research for women continues to be an urgent priority. Prior to the availability of HIV treatment women were 10% less likely than men to die from AIDS defined illnesses. In today’s HIV treatment era, however, women are 20% more likely than men to die from AIDS. While research has answered key questions and has provided specific strategies and treatments to reduce mother-to-child transmission, research must now seek to gain greater insight into gender disparities in treatment successes.
    There is a critical need for research that seeks to understand the relationship between women’s reproductive health, gender and economic inequalities and HIV prevention and treatment. United States’ health policies and programs that are designed to reduce the risk of HIV and other sexually-transmitted infections must be improved to explicitly address overall economic disempowerment among women, as well as disparities in poverty among ethnic populations. Research is needed that will help provide the data necessary to make those improvements.
    There is a critical need for increased involvement of women in the design and implementation of research. It is understood that HIV prevention and treatment research must include growing numbers of adolescent and adult women. Low retention rates for women in HIV research studies are believed to be influenced by study designs intended for men, but were later altered to accommodate women.
    There is a critical need for research involving men who report primarily having sex with women (MSW). The majority of HIV positive women report being infected through heterosexual intercourse or through intravenous drug use. Few studies have focused on the prevention and linkage to healthcare needs of men who primarily identify as having sex with women.
    There is a critical need for research in genetics, pathogenesis, and pharmacology of HIV positive and negative women. Understanding women’s physiologic risk; resilience; genetics; drug efficacy; dosing requirements and variables such as pharmacogenomics, is key to enabling adherence, improvements in health and quality of life, and the specific, gender-based care women need and deserve.
    Thank you and Sincerely,
    Anne Davis

  15. More research more funding healthier happier people

  16. Barry Brewer says:

    It is apparent to me from the content of these comments that most readers are not aware of the clinical trials that are demonsrating what is being called a “functional cure” by many scientists and many media publications.
    There should be much new info regarding these clinical trials from the upcoming CROI conference.
    Until then I suggest a visit to the Sangamo Biosciences website.