Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Introduction To The Cape Town PrEP Study Pre-Exposure Prophylaxis (PrEP) and HIV The global toll of new HIV infections - more than four million new HIV infections occurred in 2006 alone - demonstrates the urgent need for effective new HIV prevention tools. Existing prevention methods such as education, counseling, and condom use are important in reducing the number of HIV infections, but have not been sufficient to stop the epidemic. Moreover, other potential prevention methods, such as a safe and effective vaccine against HIV, are still many years in the future. Pre-exposure prophylaxis (PrEP), therapy taken to prevent rather than treat an infection or illness, is one strategy being studied by the NIH as part of its effort to develop new HIV prevention tools. In monkey studies, treatment with HIV antiretroviral drugs significantly reduced infections among monkeys exposed to the simian version of HIV. In humans, HIV has also been shown to be vulnerable to this type of pre-infection intervention. For example, antiretroviral treatment of an HIV-infected mother during childbirth reduces an infant’s chance of contracting the virus by about 75 percent. Treatment with anti-HIV drugs can also significantly reduce the risk of infection when taken immediately after exposure to the virus (PEP). The Cape Town PrEP Study The Cape Town PrEP study is a Phase IIb “proof of concept” study sponsored by the National Institutes of Health (NIH) and funded by the Bill and Melinda Gates Foundation, both in the United States. This study is designed to determine whether use of the HIV antiretroviral drug Truvada® (tenofovir disoproxil fumarate and emtricitabine) may help prevent HIV infection among people at high risk for HIV infection, when combined with safer sex counseling and condoms. A highly qualified team of researchers in Cape Town is conducting this study. The study will enroll 200 healthy, sexually active HIV-negative men who have sex with men (MSM) who are at high risk of HIV infection. The study will be conducted at the Desmond Tutu HIV Foundation in Cape Town. Potential volunteers are extensively interviewed to ensure that they understand the study and that their participation is completely voluntary. All study participants will receive condoms and counseling on how to prevent HIV infection, along with medical care for any sexually transmitted infections. Approximately half will also receive the study drug Truvada® once daily, and half will receive a placebo. Neither the study personnel nor the volunteers will know who is receiving the drug and who is receiving placebo. Study volunteers will receive safer sex counseling and will be tested for HIV and for other sexually transmitted infections monthly. In addition to extensive safer sex counseling, volunteers will be counseled that, even if they receive the study drug, there is no assurance that the drug will offer any protection against HIV - meaning safer sex precautions should always be used. At the end of the study, the investigators will compare the number of HIV infections in the group that received the drug to those in the group that received placebo, to determine if Truvada can effectively help to prevent HIV infection when used in combination with safer sex counseling and condoms. Finding a potential difference between the two groups requires a large number of volunteers because the extensive risk-reduction counseling provided to study volunteers generally lowers HIV risk behavior in both study groups. Volunteers will be carefully monitored throughout the 24-month study period and for 6 months afterwards. In addition to the possible usefulness of Truvada® in HIV prevention, the study will also assess the effects of taking a daily pill on HIV risk behaviors; adherence to and acceptability of the regimen; and whether use of the drug for prevention causes drug resistance in volunteers who become infected with HIV. Volunteers will be monitored monthly for any possible side effects or abnormalities, and the study drug will be promptly discontinued if any serious concerns are identified. If, despite extensive safer sex counseling and the availability of condoms, a volunteer becomes HIV-positive during the study, they will receive full medical care, including treatment for HIV infection if needed. Truvada was selected for the Cape Town PrEP study because it has been shown to be a safe and effective treatment for HIV, with few side effects in studies involving more than 15,000 people worldwide. Tenofovir®, one of the component drugs of Truvada®, was approved by the Food and Drug Administration (FDA) in the United States in 2002. The tenofovir plus emtricitabine combination pill used in this study was approved for use in the United States in 2004, and in South Africa by the Medicine Control Council (MCC) in 2007. More than 100,000 HIV-infected people around the world have now used these drugs. A trial of tenofovir for HIV prevention has been recently completed by Family Health International in West Africa. This study confirmed the safety of tenofovir used daily in HIV uninfected women, and found that the HIV risk behavior of volunteers declined during the study, likely because of the counseling provided. Eight women became infected during the study: 6 in the placebo group and 2 in the tenofovir group. The West African study provides a solid basis for larger studies needed to learn whether HIV PrEP can effectively prevent HIV. Commitment to HIV Prevention in Cape Town Investigators at the Desmond Tutu HIV Foundation have an outstanding record of conducting HIV prevention research. The Cape Town study site has recruited more than 1,000 people at risk of HIV into research studies since 1996, and has demonstrated outstanding compliance with international clinical trial standards. Another reason for conducting this study in Cape Town is the impact of HIV among MSM here. Studies indicate that prevalence of HIV infection in MSM is 10% in town and up to 35% in townships – underscoring the need to conduct HIV prevention research in the communities in which new prevention tools are needed most. Consultation with and the participation of local affected communities has been a cornerstone in developing the Cape Town PrEP study. Researchers consult regularly and on all aspects of the study with a Community Advisory Board (CAB) comprising leaders of HIV/AIDS service organizations, LGBT community activists, and members of the at-risk community. CAB members have participated in the developing the study design, the informed consent process, and study recruitment strategies; as well as in educating the community about the trial. The government of South Africa has also helped oversee the development of the study. Finally, the study investigators have consulted widely and on an ongoing basis with community leaders and government officials to ensure that the Cape Town study is responsive to the needs of people in the region who are at risk of contracting HIV. The NIH is sponsoring, and the Bill and Melinda Gate Foundation is funding the Cape Town PrEP study through a grant to the J. David Gladstone Institutes, a non-profit independent research organization affiliated with the University of California, San Francisco. The study is being conducted at the Desmond Tutu HIV Foundation at the Institute of Infectious Disease and Molecular Medicine, University of Cape Town Faculty of Health Sciences. The NIH and the Bill and Melinda Gate Foundation are currently supporting other studies of HIV PrEP among MSM in the Brazil, Ecuador, Peru, Thailand, and the United States. Data from the Cape Town PrEP study are expected to be available in 2010. For questions, please contact Earl Burrell at [email protected] or on 021.650.6969. Frequently Asked Questions 1. What is the purpose of the Cape Town PrEP study? The Cape Town PrEP study is a Phase IIb “proof of concept” study designed to determine whether Truvada®, a drug that is already being used to treat people with HIV infection may also help prevent HIV infection in people who are HIV-negative. 2. Why are new HIV prevention methods needed? More than four million people became infected with HIV in 2006, indicating that current HIV prevention methods are not adequate. While HIV prevention counseling has been shown to reduce HIV infections, education and counseling are not sufficient to stop the epidemic, and other prevention methods - such as a safe and effective vaccine - are not likely to be available for many years. The need for new prevention methods is critical, particularly in places where HIV is spreading rapidly such as Africa, which is the most impacted continent. 3. What is Truvada®? Truvada® is a medication for HIV infection that combines two drugs, tenofovir and emtricitabine, in a single tablet taken once daily. Truvada® has been approved by the MCC in South Africa and the FDA in the United States and is used around the world to treat HIV/AIDS. 4. Why was Truvada® selected for this study? Truvada was selected because it has been shown to be safe and effective with few side effects in studies involving more than 15,000 people worldwide, and because the drug was shown in studies to prevent the transmission of the monkey version of HIV (simian human immunodeficiency virus, or SHIV) without serious side effects. Truvada® is taken orally only once daily, remains in the bloodstream for many hours, and was well tolerated in safety trials involving people not infected with HIV. More than 100,000 persons have taken the drug since its approval. 5. Has this approach to prevention been studied before? Yes. Drugs are taken to prevent malaria, and can be used to reduce the risk of developing tuberculosis and meningitis. The possibility that a drug for HIV treatment could be used to prevent HIV infection has been studied in monkeys with very positive results. In addition, drugs used to treat HIV reduce transmission of the virus from mother to child by about 75 percent. 6. Where else are PrEP studies being conducted and who is supporting them? PrEP for HIV is being studied among MSM in Brazil, Ecuador, Peru, Thailand, and the United States. These studies are being sponsored by the NIH and funded by the NIH or the Bill and Melinda Gates Foundation. A study in at-risk women in Cameroon, Ghana, and Nigeria that was completed in 2006 confirmed the safety of tenofovir, a component of Truvada®, the drug being studied in the Cape Town trial. That study was sponsored by Family Health International with support from the Bill and Melinda Gates Foundation. 7. How will the Cape Town PrEP study work? The study is designed to determine whether Truvada® is effective in preventing HIV infection when combined with safer sex counseling and condom use. The study will also examine side effects from the study drug. The study will enroll 200 HIV-negative MSM in greater Cape Town. Participants will be randomly divided into two groups. Both groups will receive medical care for any sexually transmitted infections, along with condoms and counseling on how to prevent HIV infection. One group will also receive the study drug Truvada® once daily, while the other will receive a placebo (sugar pill). No one, including the study personnel, will know who is receiving the treatment and who is receiving the placebo until the study is finished. Participants will receive intensive counseling in safer sex practices. They will be monitored for the 24 months in which they receive study drug or placebo, and for 6 months afterward. 8. How will study participants be selected? Study volunteers must be men who have sex with men, at least 18 years old, HIVnegative, healthy, sexually active, and at high risk for HIV infection. Volunteers are extensively interviewed to ensure that they understand the study and are participating voluntarily. They receive complete information about HIV infection risk behaviors, the study drug, the purpose of the study, and what is required of them. Volunteers will be recruited through outreach to the MSM community. Information about the study will be made available at community events, over the Internet, and through recruiters who visit places where MSM meet. All outreach efforts emphasize that participation is voluntary. 9. Who is conducting the Cape Town study? The study’s principal investigators are Dr. Robert Grant (University of California, San Francisco, and the Gladstone Institutes, United States) and Dr. Javier Lama (IMPACTA, Peru). The co-investigator is Dr. Linda-Gail Bekker (Desmond Tutu HIV Foundation, South Africa). 10. Who is sponsoring and funding the study? The Cape Town study is being sponsored by the Division of AIDS at the National Institute of Allergy and Infectious Diseases (NIAID), which is part of the NIH in the United States. The study is being funded by the Bill and Melinda Gates Foundation in the United States, through a grant to the J. David Gladstone Institutes, a non-profit independent research organization affiliated with the University of California at San Francisco. The company that manufactures Truvada®, Gilead Sciences, is donating the study drug but is not providing funding for the trial. 11. What is the role of the drug company, Gilead Sciences, in the study? Other than donating the drug, the company that makes Truvada® has no role in the design, implementation, or evaluation of this study. 12. Where will the study be conducted? The study will be conducted at the Desmond Tutu HIV Foundation, Institute of Infectious Disease and Molecular Medicine, University of Cape Town Faculty of Health Sciences. This site was selected for its strong experience in clinical research; its capacity to involve their communities in carrying out this study; and its capacity to comply with all regulatory aspects of the study, including providing safeguards for participants. This is a not-for-profit organization that has no financial ties to the drug manufacturer. 13. Why is this study being conducted in MSM? This study is being conducted among MSM in Cape Town because it is important to ensure that Truvada® is safe and effective in those populations most in need. Conducting the study in a population that would be most likely to benefit, such as MSM, will also establish a strong infrastructure that will help ensure that the drug reaches the people who need it in the future, should it prove safe and effective. PrEP for HIV prevention is being studied in the populations most at risk in other countries as well – among MSM in Brazil, Ecuador, Peru, Thailand, and the United States. Study volunteers are active and informed participants and contributors to the study. All volunteers will undergo an intensive informed consent process that lays out the details of the trial and its potential benefits and risks. All participants in the study will receive intensive counseling and free condoms, which is expected to reduce the risk of infection in both the study drug and placebo groups. Participants are encouraged to ask questions and to discuss the trial with others they trust, including other medical experts, and are free to leave the trial at any time without repercussions. 14. Why is the study being conducted in Cape Town? Cape Town was selected for this study because MSM in Cape Town are highly affected by the epidemic. Studies indicate that prevalence of HIV infection in MSM is 10% in town and up to 30% in townships. Investigators in Cape Town have an outstanding record of conducting HIV prevention research, with high recruitment and retention rates of study volunteers. The Cape Town study site has recruited more than 1,000 people at high risk for HIV into research studies since 1996. The Cape Town site has also outstanding compliance with international clinical trial standards. The government of South Africa has taken strong leadership roles in HIV prevention, and understands the importance of HIV research and how it can benefit its’ citizens. It is essential that prevention research take place where the epidemic is. Since 90% of new HIV infections occur in Africa, Asia, and Latin America, it would not be correct for this research to be done only in the United States and Europe. 15. How has the community been involved in the study design and planning? Consultation with and the participation of affected communities has been a cornerstone of the development of this study. Study investigators consult regularly and on all aspects of the study with a CAB comprising leaders of HIV/AIDS service organizations, LGBT community activists, and members of the at-risk community. Discussions with the CAB began with the start of study planning (June 2007), continue today, and will continue throughout the study. CAB members have participated in the development of the research design; development of the informed consent process; recruitment; and in educating the community about the trial. In addition, the investigators consult widely and on an ongoing basis with others, including community leaders and government officials. 16. Is this study fully compliant with all ethical standards? Yes. The study is fully compliant with the Declaration of Helsinki and all other ethical standards. 17. How are study volunteers protected? Volunteers are protected through extensive scrutiny of the study before it is implemented, extensive briefing to ensure they understand the study and all of their rights as volunteers, and careful monitoring both during and after the study period. All study plans and materials have been extensively reviewed by the Institutional Review Boards (IRBs) at the University of Cape Town in South Africa and the University of California, San Francisco. These institutional review boards meet all applicable international standards. The study was also reviewed and approved by the MCC in South Africa and the NIH and FDA in the United States. Study volunteers are extensively counseled about the purpose of the study and how it will work, the fact that they might receive a placebo, and the need to strictly maintain safer sex precautions. All volunteers must sign an informed consent document and are required to pass a comprehension test to demonstrate that they understand the study and their rights as volunteers. All volunteers will receive regular HIV testing, risk reduction counseling, and condoms throughout the study and will be closely monitored for any concerns or problems - such as the emergence of toxicities or drug resistance. Volunteers are free to withdraw from the study at any time and for any reason. The study will be monitored by a Data and Safety Monitoring Board (DSMB), an independent group of clinical research experts, statisticians, and other representatives of the international academic research community, including representatives from South Africa. This group is independent and is not part of the research staff of the study. The DSMB may recommend that a trial, or part of a trial, be stopped if there are safety concerns, or if they believe that the trial objectives either have been achieved or cannot be achieved. 18. What compensation will study volunteers receive? Participants will be reimbursed for their transportation expenses to go to the study clinic and for the time spent at each study visit. Participants will also receive treatment as needed for curable STIs at no cost. Hepatitis B vaccination, a preventive public health intervention, will be offered at no cost to those participants who need it. 19. Why does this study use a placebo? No one knows whether PrEP with Truvada® will be effective in protecting people from HIV infection. Reliable information about the effectiveness of PrEP with Truvada®, which is needed to guide public health authorities at the national and international levels, can only be obtained by comparing the active drug with a placebo among people who all receive standard prevention interventions. 20. Do you need people to become infected to demonstrate whether PrEP works? Study personnel are committed to helping volunteers reduce their risk of HIV infection. Some persons will learn to protect themselves with intensive counseling, but some will not - which is why we look for new prevention methods such as PrEP or a vaccine. If infections are lower in the group that received Truvada®, it may mean that Truvada® is effective as a PrEP intervention. If the rate of new infections is low in both groups, very valuable information will have been gained about ways to provide counseling that effectively reduce HIV risk. The large size of the prevention studies helps assure that some information will be learned even if the great majority of people learn to protect themselves. 21. What happens if a study participant becomes HIV positive during the study? If, despite safer sex counseling and provision of condoms, a participant becomes infected with HIV during the study, infectious disease specialists with expertise in HIV care will follow him at the study clinic. The study will provide primary care and laboratory testing for viral load, CD4 T-cell counts, and drug resistance, which are often the most expensive parts of HIV treatment. If antiretroviral therapy is warranted, the government of South Africa’s free ART rollout clinics will provide them. 22. Does Truvada® have side effects? While all HIV drugs have some side effects, Truvada® is a widely used in part because its side effects are generally mild. In previous studies in HIV-infected individuals, less than 1 percent of study participants stopped Truvada® therapy because of side effects. The most commonly reported side effects from use of Truvada are nausea, vomiting, diarrhea, and flatulence. These effects have largely been reversed after use of the drug was discontinued. The study will monitor the health of the participants very carefully, and will stop the study drug if there is any sign of illness due to participation in the study. Anyone who has trouble will be monitored and cared for until the signs of illness resolve. 23. What is HIV drug resistance and why is it a concern in this study? Like many pathogens, HIV can develop resistance to drugs used to treat it. Theoretically - if a person is receiving a drug to prevent HIV infection and becomes infected - the fact that the virus is exposed, even briefly, to the drug being taken for prevention could cause it to develop resistance to that drug, making that drug, and possibly others like it, less effective for treatment. Previous studies indicate that it is more difficult to develop resistance to Truvada® than to other HIV drugs. In studies involving tenofovir, a component drug of Truvada®, animals that eventually became infected despite exposure to the drug for prevention did not develop drug resistance. Drug resistance also generally does not occur when drugs are used to prevent malaria, tuberculosis, or pneumonia. 24. What precautions are being taken to minimize the risk of developing HIV drug resistance for volunteers in the study who become infected with HIV? The Cape Town study involves several safeguards designed to reduce the risk of drug resistance. Volunteers will be tested for HIV twice before starting the study, and participants will be tested for HIV frequently throughout the study to ensure that, if they do become infected, the study drug is stopped before resistance can occur. The fact that this study employs a combination of two drugs also makes it less likely that resistance to both drugs will occur. Any participant who becomes infected with HIV during the trial will receive appropriate medical treatment. The study will provide viral load testing and CD4 T- cell counts, as well as drug resistance testing using three different laboratory tests (genotype, phenotype, and a sensitive point mutation assay). Although drug resistance is not expected to occur during the study, any unexpected evidence of drug resistance will be reported to an independent DSMB, which will recommend whether the trial should continue. In the unlikely event that a study volunteer develops any resistance to Truvada®, many therapies would still be fully active to treat their HIV infection, including AZT, nevirapine, and efavirenz, and all protease inhibitors, which block HIV replication at a different point than Truvada®. 25. What medical care is provided for study volunteers? Careful medical monitoring and care is provided to volunteers throughout the study. In addition to primary medical care and treatment of sexually transmitted infections, study volunteers will receive all appropriate laboratory tests to monitor for possible HIV infection or any other blood abnormalities. These tests are known as CD4 T-cell, viral load, and drug-resistance testing. Volunteers will also be monitored and treated if needed for any side effect that may be related to the study drug. If a volunteer contracts HIV during the study, treatment with antiretroviral drugs will be available through government programs. The government of South Africa’s free ART rollout clinics will help provide antiretroviral treatment to all who require it. 26. How will participants and the community benefit from the study? Study participants will benefit from extensive and ongoing HIV prevention education and counseling, including provision of free condoms at every visit. Volunteers will also receive testing and treatment for HIV and sexually transmitted infections, and testing for hepatitis B. Volunteers whose laboratory tests show that they are susceptible to hepatitis B will be offered free vaccination. If Truvada® is proven to be safe and effective in preventing HIV infection, some study participants will have been among the first to receive it. All participants, regardless of the study results, will make an important contribution to future HIV prevention efforts in their own community. 27. If Truvada® prevents HIV infection in the study, will it be practical for broad use? How will it be made available? If Truvada® is found to be highly effective at preventing infection with no serious side effects in the Cape Town study and at other sites, the Cape Town study team will work closely with national and international health organizations to develop guidelines for use of the drug for HIV prevention in high risk persons who are also receiving counseling, condoms, and care for sexually transmitted infections. These efforts would include additional research to optimize counseling for people at risk and use of the drug for prevention. The study investigators are also working with drug manufacturers and Departments of Health to help ensure that effective drugs will be available for both treatment and prevention. Tenofovir, one of the drugs being used in this study, is already available from generic drug manufacturers. 28. Is there a risk that people in the study will feel that they are protected and will increase their risk behavior during the study? Study volunteers will be counseled that PrEP with Truvada® is experimental, and that it is not known whether it will protect them against HIV infection. Still, there is a concern that some people may feel protected and may relax safer sex precautions. This concern was also expressed when HIV preventive vaccine trials were first introduced, and after the advent of PEP. However, analyses of risk behavior during vaccine trials and studies of PEP indicate that risk behavior actually decreases during these studies because of the counseling provided. Volunteers in other PrEP studies have reported fewer sexual partners and increased condom use during the study, which likely reflects the benefits of counseling and condoms. Several steps are taken in this study to ensure that volunteers continue to protect themselves. Volunteers are counseled that the pill they receive may not protect them, and the investigators will not allow a potential volunteer to enroll in the study unless he understands what a placebo is and the importance of following HIV risk-reduction measures. In addition, the investigators will closely evaluate risk behavior and the incidence of sexually transmitted infections during the trial, and will alter the counseling provided to volunteers if they detect an increase in overall risk behavior. 29. Why have other PrEP studies been stopped? Studies of Truvada® or one of its component drugs, tenofovir, are successfully under way in the United States, Botswana, and Thailand and this PrEP study has been successfully launched at the Ecuador and Peru sites. Another study has been completed in West Africa. However, PrEP studies were halted before they began in Cambodia and Malawi for a variety of reasons, including misunderstanding and miscommunication about the purpose of the study, and what care would be available for participants who become HIV positive despite the provision of intensive risk reduction counseling and condoms. Sites in which studies are now successfully under way have learned from the experience of other study locations and have made extensive efforts to address and prevent the types of concerns that arose at those sites. The investigators and sponsors of the Cape Town PrEP trial are committed to open communication, provision of comprehensive prevention measures to all participants, and appropriate treatment of any illnesses or side effects that result from participation in the study and for any volunteer who becomes HIV-infected during the study. Eligibility Criteria The target population for this multi-centre trial was developed to capture homosexual men who self-identify, are aged 18 years or older, who are at especially high-risk for HIV infection, and who consent to participate in this study. Male sex (at birth). This study aims to study the toxicity and efficacy of chemoprophylaxis for the prevention of HIV transmission in men only Willing and able to provide written informed consent as required by GCP and the ethical standards of South Africa Age 18 years of age or older in keeping with the legal age of Informed Consent in South Africa HIV-1-uninfected as necessary to determine toxicity and efficacy of chemoprophylaxis for the prevention of HIV-1 transmission Evidence of high risk for acquiring HIV-1 in order to ensure an adequate number of primary outcome observations (HIV-1 infection) to power the study and statistically determine the efficacy of the chemoprophylaxis being tested. These criteria include any ONE of the following: o No condom use during the last receptive and/or insertive anal intercourse with a male HIV-positive partner or a male partner of unknown HIV status during the last 6 months o Anal intercourse with more than 5 male sex partners during the last 6 months o Exchange of money, gifts, shelter, or drugs for anal sex with a male partner during the last 6 months o Sex with a male partner and STI diagnosis during the last 6 months or at screening o Sexual partner of an HIV-infected man with whom condoms are not consistently used Able to provide a street address of residence for themselves and one personal contact who would know their whereabouts during the study period to enable study staff to retain recruited MSM cohort and contact participants in order to convey any pertinent information pertaining to the study Ability to understand and speak a local language (English, Xhosa, or Afrikaans) for which an informed consent form has been approved by the University of Cape Town, Ethics Review Board as well as the University of California, San Francisco, Institutional Review Board before use These inclusion criteria were developed with previously gathered information from previous research conducted by the Desmond Tutu HIV Foundation within this demographic in Cape Town, input from local LGBT social advocacy groups, as well as in coordination with our international partners.