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The Fight Against AIDS Evolves (again)::
How new developments in prevention research
may change the way we do AIDS work
Over the last quarter century, the fight against AIDS has gone through significant changes. From the identification of HIV as the cause of AIDS to the discovery of treatments for HIV and opportunitistic infections, advances have saved countless lives. But lessons from past tell us that we must think critically about the who’s, where's, when's and how's of rolling out new scientific advances.
Now, next-generation prevention research -- including rectal and vaginal microbicides, pre-exposure prophylaxis, and circumcision — brings a new set of promises, and challenges. Key issues to be addressed on the latest developments in AIDS prevention research include:
• How good is good enough, when it comes prevention methods that fall short of 100% effectiveness?
• Who will get new prevention tools?
• Who will pay for them?
• What will the new standard of care be, as the lines between treatment and prevention start to blur?
• Will we still be able to develop a vaccine?
Tuesday, November 14th
6:30 - 8:30PM
LGBT Community Center, New York City
Speakers:
Kevin Fisher, AIDS Vaccine Advocacy Coalition (AVAC)
Edd Lee, AVAC
Click here for powerpoint
Co-sponsors:
AIDS Vaccine Advocacy Coalition (AVAC), Center for HIV Law and Policy, Community HIV/AIDS Mobilization Project (CHAMP), Gay Men’s Health Crisis (GMHC), LGBT Community Center, and Treatment Action Group (TAG)
Summary
“AIDS Prevention Evolves (Again): Why We Are on the Verge of an Era of New Complexity”
Notes:
(1) This presentation is based on Chapter 4 of the 2006 AVAC Annual Report, which is available at http://www.avac.org/reports.htm
(2) Julie Davids and Emily Bass were unable to come due to late-breaking extenuating circumstances.
Edd Lee, AVAC
Below is a summary of Edd’s remarks:
We have made a lot of progress in terms of understanding the human immune system and how HIV operates. In 2006, we are now on the verge of new breakthroughs to understand HIV/AIDS and on developing new tools to fight it.
How HIV has changed over the years
At the beginning of the epidemic, the focus was on the development of treatments because there were no treatments early on. Activists, educators, and researchers also worked against HIV/AIDS stigma and hit the street to raise awareness. The major populations associated with AIDS were dubbed (tongue-in-cheek, of course) the “Four-H Club” – homosexuals, hemophiliacs, Haitians, heroin addicts.
Changes and innovations to deal with the HIV/AIDS epidemic have occurred since the early 1980s. Today, there is access to treatment, research to develop vaccines, and behavioral interventions to prevent HIV/AIDS (that is, individuals change behavior to protect oneself). People living with HIV/AIDS and people affected by HIV/AIDS are connected to services to support them. The populations affected by HIV/AIDS have changed and expanded to disproportionately affect people of color, women, youth, and people in developing countries. There has been a marked globalization of HIV/AIDS.
More Change Is on the Way
Currently, a range of new prevention strategies is in advanced stages of research. In the next five years, data will be available from several end-stage clinical trials, including male circumcision, microbicides, AIDS vaccines, pre-exposure prophylaxis (PrEP) and treatment of HSV-2 infection. Data from these studies will indicate if these tools and strategies protect against HIV infection.
The current debate about HIV testing represents the beginning of a new era, as the debate is an indicator of change of how we deal with AIDS. The testing debate grapples with whether HIV screening should be routine or mandatory, whether HIV/AIDS stigma affects the informed consent process, and if treatment really is more available for those who learn they are HIV-positive.
The global roll-out of treatment also changes the way that we talk about and experience HIV/AIDS
Timeline of Next Five Years
2007
• Phase III study of acyclovir for the reduction of acquisition of HIV in high risk, HIV negative, HSV-2 seropositive individuals.
• Project Unite study of different risk-reduction interventions for HIV vaccine trials.
• Analysis of male circumcision trials – does it have an impact on transmission of HIV (both as transmitting and acquiring HIV)?
• Phase III study of the diaphragm to prevent HIV acquisition among women.
2008
• Phase III of behavioral interventions study. Determine how well community mobilization, mobile testing, same-day results and post-test support for HIV in sub-Saharan and Thailand reduces HIV transmission in those communities.
2009
• PrEP trials data of ARV prophylaxis against infection: HIV negative people take ARV drugs (tenofovir or truvada in current studies) and see if they are protected from HIV infection if exposed to HIV.
• Data from five microbicide efficacy trials. Microbicides are usually gel formulations for women use with or without knowledge of partner in order to protect her from HIV.
• Phase III trial of HSV-2 suppression in serodiscordant couples: see how HSV treatment for HIV-positive individuals will prevent or reduce his/her ability to pass HIV to someone else.
2010
• Big year for AIDS vaccines: Prime-boost Phase III trial in Thailand, which tests a combination that includes AIDSVAX (it failed when tested alone) with ALVAC vCP1521. There are 16,000 participants.
2011
• Results for Phase IIb proof of concepts trial for AIDS vaccine made by Merck — but scientists do not expect it to stop HIV infection. It may delay course of HIV disease if a person becomes infected by preventing the individual from getting sick for 20 or 30 years instead of 10 years.
2013
• Data from a study to see if treatment of HIV with HAART (highly active anti-retroviral therapy) reduces the ability of an HIV-positive person to transmit HIV to others who are not infected.
The fact is that so much data coming begs questions.
Implications
• We must evaluate our knowledge. We need to conduct more research and make better research agendas.
• What kind of research agendas do we need to set to get clearer data from these trials? Decisions must be based on conclusive data. For example, PrEP trials do not provide a clear answer for prevention of HIV transmission between women and men. Data from the trials only determines if PrEP works for gay men.
• Many implementation questions must be raised: How will we use this information? How do we use these new tools if we find that microbicides work 60% of the time to prevent HIV, diaphragms 40%, etc.? Which one do we use? Do we use them all together? Who gets these tools first? Generally, the developing world gets stuff 10-15 years later than the developed world. However, this does not work because the burden of HIV disease is on the developing countries.
• How do you talk about partial efficacy for people? How do we keep them from being confused? New tools and strategies must be used in a way so not to worsen the epidemic. How do you talk about disease modulation as a beneficial thing when it only changes the course of AIDS but does not prevent it? How do you talk about reducing infectiousness? These topics and issues are tough things to talk about in communities.
• What are the implications for future research in terms of trial design (size, location and incidence rate) and the standard of care during the trials?
Prevention Trials
This research question is asked in all prevention trials: Does this strategy decrease the risk of HIV infection more than the standard prevention package provided by the study?
In clinical trials for prevention products, participants go through an intense informed consent process so that research will be conducted ethically. This informed consent process involves the delivery of information about how many times a participant will come in, about the product being evaluated, and the benefits and risks of participating in trial.
So, the researcher enrolls a population of people, finds out their rate of HIV infection, and randomizes them into two groups. One group gets the experimental tool and the other group gets the standard of care. The current standard of care in research includes risk reduction counseling, condom availability, and clean needles (sometimes). However, the standard of care is often not really standard. Therefore the researcher must improve the standard of care available to the studied population in the clinical trials. If the researcher improves the baseline standard of care, then it is harder to see if the new product works because the researcher reduces the trial population’s HIV infection rate. In order to get around this, the researcher has to recruit more people for the trial and it takes longer. In the end, such complications of clinical trial design pose a challenge in the development of more prevention tools.
Other complicated issues arise as well, namely what the trial participants should get as a good standard of care package for a clinical trial. For example, how do you control for male circumcision? A researcher cannot make everyone get circumcised in order to control for this. How many new prevention strategies does the researcher provide to the participants?
In the context of research, how do you explain that none of these prevention strategies is likely to be 100 percent effective in stopping HIV transmission? How does the researcher discuss nuanced concepts such as partial efficacy, disease modulation, and reduction of infectiousness in a way that the participant really understands the risks and benefits of participating in the trial?
Prevention research linked to treatment advocacy
For example, right now with prevention for positives, we only have condoms and behavioral intervention counseling. But soon we can offer more tools for them, like microbicides. In developing countries, we can offer PrEP, microbicides or female diaphragms for everyone in the family.
• How does prevention and testing get incorporated into treatment roll-out and care?
• Who gets tested and how? Families, couples, individuals, routine, voluntary, in-patient?
• As ARV programs roll out, different countries and different clinics in the same country are providing testing in very different ways.
• ARV programs mean that the population being reached for prevention initiatives is different (i.e. for HIV+ individuals, families, partners, etc.).
• What’s the best prevention package to offer people living with HIV/AIDS? What about their families and their partners?
Community Involvement
Community involvement is very important in research. This was a key component of beginning of the fight against HIV/AIDS.
New products do not make a difference if people do not know about them, trust them or use them. The community must be involved in deciding how good is good enough and what products are available in each country. The community must be involved in decision-making and needs to decide what combination of products is best for them. Perhaps it would be one product or another, or maybe it would be a menu of products available to them.
Questions and responses from Audience
Question: Incidence is not seen at such a high rate in prevention trials. One explanation for this is that these trials may reach a savvier population. In conducting these trials, do researchers actually reach high-risk populations? How does the researcher reach them?
Edd: There is one US trial that is running well with the incidence rate they anticipated for it. This is interesting because the US has most resources and best community education around HIV/AIDS. The main issue that impacts it is surveillance — is there good epidemiological evidence/data? If there is not good data, the researcher can take a snapshot. In developing countries, people tend to be so engaged in changing their HIV risk behavior that incidence changes. Community education and prevention work to lower the rate of HIV in their country because it took so long to scale-up capacity to do research. It is easier to do research in settings where there is a more stable public health infrastructure. In US, we know the populations; they are specialized and researchers know what is going on here.
Kevin: Also, there is a lot of play in the incidence numbers for the researchers.
Comment: During prevention trials, people have access to condoms and risk reduction counseling, which is artificial access to HIV prevention tools. When the trials end, even if the participants know what is going on, they will not have access to the tools.
Kevin: Yes, in trials people do much better.
Comment: In behavioral prevention trials, the ones proven effective are implemented. Yet, the results indicate a potentially false effectiveness because there is an ideal setting to get these outcomes.
Edd: This may be true — but few behavioral interventions measure effectiveness by level of HIV transmission, and instead employ a measure like “willingness to change.” The “Explore” studies are the first large-scale study to test if behavioral intervention actually impact HIV transmission.
Comment: The timeline showed a lot of medical interventions, but what is out there in terms of behavioral interventions?
Edd: The Phase III trial in Sub-Saharan Africa and Thailand are the biggest ones. There are always lots of small trials going on, but these large-scale trials are what you see. I do not know how much large-scale research will be seen out of the US due to government reorganization. There is now a focus on biomedical interventions.
Comment: Research for behavioral interventions is more in line with the trend for prevention to be increasingly relegated to the medical setting.
Edd: HIV testing is put in clinical setting. These tools don’t have to happen in medical setting. Cervical barriers, microbicides and condoms can be over-the-counter products. The question to ask is do you have to see a doctor to get these things or can you have access to these things outside of a medical setting?
AVAC Recommendations
There is a need to convene World Health Organization (WHO)/UNAIDS/civil society-sponsored ethical consultations on issues related to introduction and evaluation of new strategies (with community involvement).
CHAMP is good at forming a prevention research network. How can we move forward faster and better? We call for a prevention research advocacy network to share and develop best practices and build a strong advocacy campaign for widespread access to known interventions: clean needles, male and female condoms, comprehensive sex education.
How do we roll out prevention tools faster? For example, needle exchange greatly reduces HIV infection and does not increase drug use, yet the US government is just not into needle exchange. The morality versus science battle will continue as we move forward and will pose challenge to whether we will end the HIV epidemic.
We must make sure that clear communications materials are available at the community level, and that people understand them.
Communications must be designed to help community members understand the different interventions (male circumcision, PrEP, microbicides, vaccines, HPV vaccines and so on) and also to know how to communicate the information to others.
Kevin Fischer, AVAC
Below is a summary of Kevin’s remarks:
This issue is all about choices.
We are being asked whether we know if these choices work, but we don’t know. Where are the advocacy pressure points so we can get the choices we want?
Who is in charge? No one. People are in charge of individual trials but no one is in charge of whole agenda. It is important that all of us make sure that nothing is dropped and develop trials in ways that make sense.
The way we develop drugs is different than the way for developing vaccines and other prevention technologies. Pharmaceutical companies are not good at developing vaccines until recently, and certainly they are not suitable at all for developing prevention technologies.
The FDA licenses products, but it has been gutted (for general background on this, see The Nation, November 20, 2006, “The Gutting of the Civil Service”). Since it could take many years to develop a prevention product, the company embarking on prevention trials needs a reasonable assurance that it will be licensed when it is done. Therefore, we need a very responsive FDA.
In 2010 we may get results that a vaccine slows the progression to AIDS or could even eliminate it. But, we won’t be able to license it unless we have another Phase III study, which could take another 5 years if done fast. So, this is the regulatory problem.
We need consistent government funders. The US government provides 3 of the 4 dollars funding HIV vaccine trials and 60% of microbicide funds. Progress can’t be made with out that funding. Yet, even though the NIH currently funds rectal microbicide research, that funding could go away (and it has been flat anyway). The same goes for the CDC, too, which funds PrEP research.
When we have partially effective vaccines and microbicides, what will we tell people about them? Those messages will be hard to develop and communicate. Pharma and the government certainly cannot come up with those messages. Therefore, we have to come up with them in way that makes sense so that individuals can make their choices.
Regarding the research agenda, researchers see things from their own point of view. In 1957 scientists came together to look at smoking and lung cancer. Basically, they said that smoking could not cause lung cancer because people who do not smoke also got lung cancer. The causal link between smoking and lung cancer did not come until later when some scientists were willing to stick their necks out.
At conferences, researchers like to characterize HIV as a clever virus, for example, that when it is transmitted it reverts back to a form enabling its easier replication. But we need to get beyond this assertion and think about ways we can beat it — like Karl Rove was clever and we beat him.
Edd Lee
There are simple things that you all can do.
• Broaden your own understanding of what it means to fight HIV/AIDS. Some people specialize – which is important – but we need to generalize about what we need to do to beat HIV/AIDS.
• Stay on top of new developments in HIV research.
• Join the Advocates’ Network at http://aidsvaccineclearinghouse.org/network.htm.
• Make sure your community gets accurate info about interventions.
• Help to develop good community practices, not just as trial participants but also by getting involved in the design of questions and implementations.
• Read the AVAC annual report (this talk is based off of Chapter 4).
Emerging adolescent agenda
We need youth to be involved in vaccine trials. Currently, no vaccine trials and no microbicides trial involve them, though one of each is being planned. A huge obstacle is figuring out how to involve them in an ethical way. Parents must consent. Parents do not want to give their daughter HPV vaccine because they do not want to encourage daughter to have sex. But what is the cost? Get HPV by clandestine sex and get cervical cancer later? It is important to pay attention to social justice implications of HIV/AIDS and be aware of the comprehensive response required to fight AIDS.
HIV AIDS Tool Kit (Slide 21)
Wouldn’t it be good if we had one as full as this is — right now only have the bold black items — it would be great that we have the things in red. Then people can choose the one that works best for them in order to protect their loved ones.
Treatment analogy (slide 22)
The reality is that the best response to HIV/AIDS is a comprehensive response that includes prevention, testing, treatment/care, research and social justice. It’s a lot like AIDS treatments – we know that mono-therapy (or just using one AIDS drug) is not the best. HIV develops mutations and eventually the drug no longer works. Instead we use combination therapy because the best way to control the virus in someone’s body is to attack it at multiple points during its replication process. Similarly, we need to attack the HIV/AIDS pandemic at multiple points if we are going to defeat it. Prevention should be thought of in the same way — it’s not just about testing and not just access to treatment or an 80 to 90 percent effective vaccine — all three things are needed to control the virus.
Social justice (slide 23)
When I talk about research into new technologies, I’m talk specifically about development of new and better treatments, microbicides and vaccines. As for social justice, I find that many people who come to this work, do so out of a concern for their own communities. HIV is a social justice issue as demonstrated by who is most impacted by the epidemic – people of color, women, sexual minorities, the poor, and drug users. Basically, the powerless.
AVAC does not take government or pharmaceutical company funding.
Questions, Answers, and Discussion
Question: Cost comes up – not just the cost of research. Some suggest that it may not be cost effective to roll out these prevention tools. From the researcher’s point of view, how does one convince the current FDA that empirical data is best way to set policy rather than other ideological factors?
Kevin: It’s best to state the argument for a prevention tool roll-out in that way — based on empirical data.
Edd: Broaden the definition of success. Though cost effective analysis has its use and purpose, if that is only measure we use, we are screwed because it won’t be cheap, easy and fast. Instead, we need social justice and human rights measures of success.
Question: What happens if people can’t pay; how can they get access?
Edd: If a researcher knows what is going on in community, then the researcher would know where to refer. Since HIV/AIDS requires a comprehensive response, a researcher really should know where to refer participants.
People like to say AIDS is not big deal, but this is a crock. You have to have access to treatment, insurance, and money to deal with AIDS. Three people on an AIDS Drug Assistance Program (ADAP) waiting list just died in South Carolina. HIV/AIDS isn’t that big of a problem any more – if you are rich. But for those of us who aren’t – which is a majority of people infected and affected – HIV/AIDS is a huge deal; it is an epidemic.
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PRESS CENTER