From Tuskegee to Transparency: An Evolution in the Ethics and Accountability of Clinical Trials Involving Human Subjects

via RH Reality Check, by Anna Forbes and Kate Ryan

People who participate in clinical trials take the enormous step of volunteering to test a product that may be useful and, sometimes, life-saving if it turns out to be effective. They play an irreplaceable role in research to prevent, treat, and sometimes cure illness – as well as to find other ways to improve people’s health and lives.

Trial participants make a profoundly personal contribution and accept potential medical, social, and personal risks on behalf of others. An ethical trial is one that eliminates or minimizes participants’ risks as much as possible, invests in making sure that participants understand clearly what they are volunteering for, and protects their rights at every step.

For example, without clinical trials, we would not have seen recent advances in antiretroviral drugs to treat HIV, long-acting contraceptive choices that allow women greater control over their use, or microbicides that may be able to protect women from HIV.

The United States government has rules to protect people who participate in federally-funded biomedical and behavioral research. The rules vary depending on which agency is supporting the research, but they all share a starting point known as the Common Rule, a set of regulations for all federally-funded research involving human participants, whether it is conducted inside or outside the U.S.

But those rules have not always been in place, and there are some shameful chapters in the history of medical research supported by the United States that include violations of the most basic standards of ethical behavior. This history has left some people deeply suspicious of clinical trials and the motives of those who conduct them. Many explain their suspicion with one word: “Tuskegee.”

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.]

Meet Yaa Simpson: Another New Friendly Rectal Microbicide Advocate!

“Stigma is only dispelled by shining a brighter light on it! We have to speak life and light with our words and actions. There is enough doom and gloom to impact everyone - and that is where stigma resides. But letting people know they have options, biomedical techniques for prevention, medications, possible vaccines, gathering more evidence, integrating creative research designs, etc. are all steps in the right direction. We must expect the impossible and believe in miracles!”

Yaa Simpson is an IRMA advocate from Chicago, Illinois. She is an epidemiologist for the Chicago Department of Health and a Community Epidemiologist for TACTS (The Association of Clinical Trial Services). She loves to contribute to ideas and discussion about better research in the community, specifically HIV/STI prevention trials. She is also working towards her doctoral degree and hopes to one day conduct HIV prevention trails in Chicago.

Yaa first learned of IRMA when she was invited to a presentation on microbicides several years ago. Here she was introduced to Jim Pickett and his work with IRMA. She remembers Jim saying, “We all have opinions, like we all have booties!” She now is an active member on the listserv and enjoys IRMA’s blog and educational teleconferences.

She believes rectal microbicides are an important tool to add to the prevention technology toolbox, and acknowledges that we must develop technologies to prevent HIV spreading through any avenue, including rectally.

Her advice for IRMA is to continue to be involved with people who want to see change! “Talk to those who don’t want to hear about it and strategize with those who are looking for answers. Be diligent and be patient. And if you ever feel discouraged or overwhelmed by the stigma associated with standing up for rectal microbicides, remember what Mark Twain once said: 'Keep away from people who try to belittle your ambitions. Small people always do that, but the really great make you feel that you, too, can become great.'”

Read more bios from Friendly Rectal Microbicide Advocates.



[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.]

Bacterial Bioshield Could Keep HIV at Bay

Via New Scientist.

A LIVING microbicide reduces HIV-like infection in monkeys, and might one day provide women with long-lasting defence against the virus.

Dean Hamer of the National Institutes of Health in Bethesda, Maryland, and colleagues engineered naturally occurring vaginal bacteria to produce the anti-HIV protein cyanovirin-N.

They applied a gel containing the bacteria to the vaginas of rhesus macaques before infecting them by the same route with a hybrid of SIV and HIV. The engineered bacteria cut the infection rate by 63 per cent (Mucosal Immunology, DOI: 10.1038/mi.2011.30).

Human females have 10 times as much of the bacteria as female macaques, so the engineered bacteria could reduce infection rates even more dramatically, says Hamer. Clinical tests could begin in a few years after safety testing.

[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.]

New, Long-Term PrEP Study Announced

Via Now Chelsea, by Sam Spokony.

Few methods of HIV prevention have been as promising, or as controversial, as pre-exposure prophylaxis (PrEP). After a history of underground practice and off-label prescriptions, the approach has recently begun to receive serious attention from researchers, policy makers and health care advocates.

An outgrowth of post-exposure prophylaxis (or PEP, a short-term antiretroviral treatment that has been used since the early 90s to decrease the likelihood of HIV infection after exposure to the virus, either occupationally or through sex), PrEP is a similar antiretroviral that can be taken by HIV-negative individuals in order to help prevent them from seroconverting (being infected).

The results of a Phase III clinical study known as iPrEx were published in the New England Journal of Medicine on November 23, 2010. The study showed that, in a group of 2,499 gay men, PrEP — in the form of a combination of drugs under the brand name Truvada — was 44 percent effective in preventing HIV seroconversion.

Under the guidance of Dr. Roy Gulick (director of the Weill Cornell Medical College HIV Clinical Trials Unit), a new experiment called the NEXT (Novel Explorations of Therapeutics) PrEP Study will begin this fall. It will include 400 at-risk, HIV-negative gay men, and will take place over 48 weeks at 12 sites across the U.S. and Puerto Rico.

The NEXT PrEP Study will differ from iPrEx in that its primary experimental group will receive a daily regimen of the drug maraviroc (brand name Selzentry). The control group will receive Truvada, and two other experimental groups will receive combinations of maraviroc and either tenofovir or FTC (the two individual drugs that make up Truvada). A major goal of the study, along with testing the HIV-prevention efficacy of maraviroc, will be to gauge the side effects of the drug on participants.

“The longest any HIV-negative person has taken PrEP in a clinical study is 12 weeks,” Gulick told Chelsea Now in a July 23 phone interview [This is actually a major factual error. For example, the average follow-up in iPrEx was 14 months - IRMA]. “Now, since this is a drug we’re giving to healthy people, the next step is exploring further to prove that it is both safe and tolerable for them.”

Read the rest here.

[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.]

HIV Vaccine News

Recently, two new discoveries which may eventually lead to a vaccine for AIDS have been made by researchers. One, being presented at the IAS Conference in Rome this week, comes from the Maryland-based VirxSys Corporation. Researchers injected non-human primates with an altered form of SIV, the primate equivalent to HIV.

(Via CNN) Over the course of six months, five infected monkeys were injected with the vaccine three times, while five others were given a placebo vaccine. After 18 months, it was found that 40% of the vaccinated monkeys had very low to undetectable amounts of virus in their bodies.

“We are well on the path to a functional cure, at least in monkeys,” says Laurent Humeau, VirxSys vice president of research and development.

“Although this pre-clinical study is modest in terms of size, it is highly unusual to see near non-detectable levels of the virus not only circulating in the blood, but also in the reservoirs where HIV is known to replicate,” said Joep Lange, M.D., Ph.D., professor of medicine at the Academic Medical Center, University of Amsterdam, and head of the Amsterdam Institute of Global Health and Development.

In the monkeys, the vaccine’s effect was sustained two years after the initial vaccination, without the need for any booster shots.

Other researchers have created similar type therapeutic vaccines. In May, Dr. Louis Picker of the Oregon Health and Science University’s Vaccine and Gene Therapy Institute announced a vaccine successful in preventing monkeys from acquiring SIV. Like the VirxSys vaccine, this was a genetically altered virus. In this case, the altered virus was CMV, from the herpes family.

But making the leap from monkeys to humans is a big step. Therapeutic vaccines "have looked really good in monkeys – but monkeys are not people and SIV is not HIV," said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Disease. "Really good concepts in primates have been duds in people.”


The other study, published last week, focused on antibodies which, if harnessed, could help the human body fight the HIV virus:

(Via US News) Researchers report that they've gained insight into the workings of the immune system's response to HIV, the AIDS virus, in certain people, potentially providing a boost as scientists work toward a vaccine.

The findings won't have an immediate big impact on either vaccine research or HIV treatment. However, they do reveal how soldiers of the immune system known as antibodies use special powers to combat the virus in some patients, said study co-author Dr. Michel C. Nussenzweig, a professor of immunology at The Rockefeller University in New York City.

Ultimately, he said, scientists could develop a vaccine that teaches people's bodies how to make the antibodies. "You'd try to make them do it themselves," he said, instead of pumping antibodies into the body.

Since the late 1990s, AIDS has largely become a treatable, chronic disease. But it can still be deadly, and many scientists think they're years away from developing a vaccine to prevent people from becoming infected in the first place.

In the new study, published online July 14 in Science, researchers focused on antibodies that are produced only in certain patients with HIV. They work by preventing the virus from picking the locks in cells that are supposed to keep germs out.

[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.]

PrEP: Prevention Revolution or Magical Thinking

One of the most exciting developments in the fight against HIV is a recent study that concluded that gay men could significantly reduce their risk of infection by taking an existing anti-HIV medication on a daily basis.


Earlier this month our friends at Feast of Fun and Lifelube hosted a forum in Chicago to discuss the iPrEx study published this winter. It was an energetic and exciting discussion with scientists, advocates, and real people taking the pill on the possibilities and concerns surrounding PrEP. For those too far or too busy to make it, Feast of Fun recorded the forum as a podcast, available for free on their website. Please check out the podcast and share your thoughts on the study.



Keith Green, Marc Felion, Dr. Bob Grant and Fausto Fernós - Forum Hosts and Participants


[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.]

Anti-AIDS Gel Also Boosts Sexual Pleasure

Via Times of India.

 South African scientists, who launched a 24-month trial to confirm the efficacy of a microbicide gel that would reduce the risk of women getting HIV, have found an unexpected spin-off – it also boosts sexual pleasure.

Wits professor Helen Rees, of the university's reproductive health and HIV institute, said the R300m trial would involve about 2,200 sexually active women at seven locations countrywide.

The Tenofovir gel study - known as Follow-on African Consortium for Tenofovir Studies (Facts) study - would be a follow-up to the Caprisa 004 study, which showed that a highly consistent use of the microbicide by women resulted in a 59 per cent reduction in the risk of HIV infection.

Rees said during a previous study involving another gel - that proved unsuccessful in the fight against HIV - participants had noted the gel improved their sexual pleasure.

"One of the big messages we got, was many women said 'We liked this', News24.com quoted her as saying. 

 

Read the rest here. 

[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.]

Starting HIV treatment when CD4 cell count dips below 500 improves AIDS-free survival

Via aidsmap, by Michael Carter

Patients who start antiretroviral therapy when their CD4 cell count dipped below 500 cells/mm3 are less likely to develop an AIDS-defining illness than individuals who start treatment with a CD4 cell count of 350 cells/mm3, an international team of investigators report in the Annals of Internal Medicine. However, initiating HIV treatment with a CD4 cell count of approximately 500 cells/mm3 did not reduce the risk of all-cause mortality.

“If the goal is to prevent AIDS-defining illness or death, our findings support cART [combination antiretroviral therapy] initiation once the CD4 cell count decreases below 500 cells/mm3,” comment the investigators.

Nevertheless, results of the study will undoubtedly inform the debate about the best time to start antiretroviral therapy.Treatment guidelines in Europe currently recommend that AIDS-free patients should start therapy when their CD4 cell count is in the region of 350 cells/mm3. However, US guidelines advocate treatment when an individual’s CD4 cell count falls under 500 cells/mm3.

Large randomised trials are currently underway to try and determine the optimum time to start HIV therapy. However, their results are not expected for several years. Because of this continuing uncertainty investigators from the HIV-CAUSAL Collaboration undertook a prospective observational study involving approximately 21,000 adult patients enrolled in cohorts in Europe and the US.

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.]

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.]

Is Africa ready for PrEP?

Via Incidence0.org, by Adebisi Ademola Alimi

One of the biggest breakthrough in HIV clinical research, since the outbreak of the epidemic 30 years ago, is the recent success in a clinical trial of a new HIV prevention approach based on the daily use of the antiretroviral drug Truvada by HIV negative person to prevent HIV transmission (Called PrEP, for Pre-Exposure Prophylaxis).

The results of the iPrEX trial raised hope but also many questions and concerns as showed by the ensuing debate about what the next step should be. Divergences culminated with the Aids Health Foundation (AHF) petitioning the FDA not to consider Gilead’s request for a licence to use Truvada for the prevention of HIV infection and a joint counter response by a number of HIV advocacy organisations.

But for me as an advocate and an African living in Europe, the most important thing on my mind is “Will Africa be able to access PrEP?” Providing ARV to HIV negative people in Africa needs to be considered in light of the challenge of accessing treatment in Africa, where more than 50% of HIV positive people in the world live (UNAIDS report).

Even if PrEP drugs become available, what are the mechanisms in place to ensure that it will not be tribalized in a continent where there are some indications that access to ARVs is based on political and ethnical loyalty and where there are evidences of bribery at the delivery point, misused of funds and a non-negligible ARVs black market leading to ARVs being dispensed to increasing numbers of patients at the periphery of the health system. One has to be skeptical about the PrEP implementation process in this context.

Read the full article

[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.]

The Truth Wears Off: Is there something wrong with the scientific method?

via the The New Yorker, byJonah Lehrer

[fascinating stuff, and very relevant to our work. a must read]

In the late nineteen-nineties, neuroscientist John Crabbe investigated the impact of unknown chance events on the test of replicability. The disturbing implication of his study is that a lot of extraordinary scientific data is nothing but noise. This suggests that the decline effect is actually a decline of illusion. Many scientific theories continue to be considered true even after failing numerous experimental tests. The decline effect is troubling because it reminds us how difficult it is to prove anything.

Read more of the summary [subscription required for the full article]


[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.]

HIV Meds for HIV Prevention.... Salvation?

via Positively Aware, by Jeff McConnell

Is ART prevention the second coming in this pandemic? 

The trials cannot tell us that. That is a question only communities threatened by HIV can answer.

Read the whole thing.


[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

How do you know if a clinical trial is ethical?

by Lori Miller, AVAC

Provide input on the draft second edition of the Good Participatory Practice Guidelines.

Join a call next week to learn more.


As the rectal microbicide field is progressing, more trials will be rolled out into communities and involve greater and greater numbers of volunteers. All stakeholders in biomedical HIV prevention research – from advocates, to community groups, to research teams and research sponsors have important contributions to make in the process of designing and conducting rectal microbicide trials.

The GPP guidelines provide trial funders, trial sponsors, and trial implementers with specific guidance on how they should work collaboratively with other stakeholders such as community members. Advocates can also use the GPP Guidelines to evaluate how well research teams are engaging community stakeholders, and if they are following the standards established in the GPP Guidelines.

The GPP Guidelines cover areas such as how stakeholders should be involved in the protocol development process, how research teams should work with community advisory boards and other stakeholders advisory mechanisms, how the standard of HIV prevention offered in any trial should be negotiated with community members , how trial results should be shared with trial participants and members of the community, as well as many other topics.

A teleconference/webinar on the 5th of October will provide an opportunity to learn about the revised guidelines and to ask questions. All stakeholders are encouraged to read the draft second edition of the GPP Guidelines and send their comments and suggestions by October 31st to UNAIDS and AVAC. Feedback on the draft second edition will then be compiled and the final version of the second edition of the GPP Guidelines will be released in late 2010.

Teleconference/webinar info

• UNAIDS and AVAC invite stakeholders in biomedical HIV prevention research to join a webinar on good participatory practice
  
• Tuesday, 05 October, 9am – 10am US Eastern time / 3pm - 4pm Geneva time
• Call-in number: US & Canada 866.740.1260
• Access code: 3671417
• Please register here for access to the webinar link

Click here to download the draft second edition GPP guidelines.
Comments on the GPP guidelines can be emailed to avac@avac.org or gpp@unaids.org.