FAQ

The iPrEx study is a Phase III study designed to determine whether tenofovir/emticitabine (FTC/TDF), a drug that is already being used to treat people with HIV infection may also help prevent HIV infection in men who are HIV-negative.

2. What is tenofovir/emtricitabine?

FTC/TDF is a medication to treat HIV infection in a single tablet taken once daily.  FTC/TDF has been approved to treat HIV/AIDS by the U.S. Food and Drug Administration (FDA) and is used in the United States and other countries.  FTC/TDF is marketed under the name Truvada®

3. Why was tenofovir/emtricitabine selected for this study?

FTC/TDF was selected because it has been shown to be safe and effective with few side effects. In studies in macaques, the drug was shown to prevent the transmission of the monkey version of HIV (simian human immunodeficiency virus, or SHIV) without serious side effects.  FTC/TDF is taken orally once daily, remains in the bloodstream for many hours, and was well tolerated in safety trials involving people not infected with HIV.

4. Has this approach to prevention been studied before?

The concept of taking drugs to prevent infection has been used to prevent malaria in and to reduce the risk of developing tuberculosis and certain types of meningitis. In addition, drugs used to treat HIV reduce transmission of the virus from mother to child by about 75 percent. The possibility that a drug for HIV treatment could be used to prevent HIV infection has been studied in monkeys with positive results. 

5. Where else are PrEP studies being conducted and who is supporting them?

Pre-exposure prophylaxis (PrEP) for HIV prevention is being studied in heterosexual men and women in Botswana, in heterosexual women in Kenya, South Africa, Malawi, Tanzania, Zambia, Uganda and Zimbabwe in intravenous drug users in Thailand, and in serodiscordant couples (copules with one HIV-positve and one HIV-negative member) in Kenya and Uganda.  These studies are being supported by local governments in the countries where the studies are occurring and by the U.S. Centers for Disease Control and Prevention (CDC), the United States Agency for International Development (USAID), the National Institutes of Health (NIH) and the Bill & Melinda Gates Foundation.

A study in West Africa completed in 2006 confirmed the safety of tenofovir, a component of the combination drug being studied in iPrEx, for at-risk women.  That study was sponsored by Family Health International with support from the Bill & Melinda Gates Foundation.

6. Where is the iPrEx study taking place?

The study is enrolling 3000 HIV-negative men who have sex with men (MSM) at 11 sites in six countries: two sites in Lima, Peru, one site in Iquitos, Peru, one site in Guayaquil, Ecuador, one site in Boston, one site in San Francisco in the United States, one site in Cape Town, South Africa, two sites in Rio de Janeiro and one site in Sao Paulo, Brazil and one site in Chiang Mai, Thailand. 

7. How does the iPrEx study work?

The study is designed to determine whether tenofovir/emtricitabine is effective in preventing HIV infection when combined with safer sex counseling and condom use.  The study is also examining side effects from the study drug. 

Participants at each site are randomly divided into two groups.  Both groups receive medical care for any sexually transmitted infections, along with condoms and counseling on how to prevent HIV infection.  One group also receives the study drug tenofovir/emtricitabine once daily, while the other receives a placebo (sugar pill).  No one, including the study personnel, know who is receiving the treatment and who is receiving the placebo until the study is finished.

Participants receive intensive counseling in safer sex practices.  All participants are  monitored throughout the study (until approximately mid-2010), and for up to six months afterward. 

8. Who is conducting the iPrEx study? 

The study’s principal investigators are Dr. Robert Grant (University of California, San Francisco, and the J. David Gladstone Institutes, in the United States) and Dr. Javier Lama (Investigaciones Medicas en Salud, INMENSA, Peru). Co-investigators include; Juan Guanira (Impacta, Peru), Dr. Kimberly Page-Shafer (University of California, San Francisco, US); Dr. Martin Casapia (Asociación Civil Selva Amazonica, ACSA, Iquitos); Orlando Montoya (Equidad, Guayaquil); Kenneth Mayer (Fenway Health, Boston, United States); Susan Buchbinder (San Francisco Department of Public Health, San Francisco, United States); Dr. Linda-Gail Bekker (Desmond Tutu HIV Foundation, Cape Town, South Africa) Jose Henrique Pilotto (Instituto de Pesquisa Clinica-Fundacao Oswaldo Cruz, Rio de Janeiro, Brazil), Dr. Mauro Schechter, (Projeto Praça Onze, Universidade Federal de Rio de Janeiro, Rio de Janeiro, Brazil), Dr. Esper Kallas, (Universidade de Sao Paulo, Sao Paulo, Brazil) and Dr. Suwat Chariyalertsak, (Research Institute for Health Sciences, University of Chiang Mai, Chaing Mai, Thailand).

9. Who is funding the study?

The iPrEx study is being funded by the Division of AIDS at the National Institute of Allergy and Infectious Diseases (NIAID), which is part of the U.S. National Institutes of Health (NIH), through a grant to the J. David Gladstone Institutes, a non-profit independent research organization affiliated with the University of California at San Francisco.  Additional funding is provided by the Bill & Melinda Gates Foundation.  The company that manufactures tenofovir/emtricitabine, Gilead Sciences, is donating the study drug but is not providing funding for the trial.

10. What is the role of the drug company, Gilead Sciences, in the study?

Other than donating the drug, the company that makes tenofovir/emtricitabine has no role in the design, implementation, or evaluation of this study.

11. Where is the study being conducted?

The study is being conducted at the Investigaciones Médicas en Salud (INMENSA) in Lima, Peru; Asociación Civil Impacta Salud y Educación (IMPACTA) in Lima; the Asociación Civil Selva Amazónica in Iquitos, all three in Peru; Fundación Ecuatoriana Equidad in Guayaquil, Ecuador; Fenway Health in Boston; the San Francisco Department of Public Health (SFDPH) in San Francisco, both in the United States, the Desmond Tutu HIV Foundation – University of Cape Town in South Africa, the Instituto de Pesquisa Clinica Evandro Chagas – Fundacao Oswaldo Cruz, in Rio de Janeiro, and Projeto Praça Onze, Universidade Federal de Rio de Janeiro; Universidade de Sao Paulo, all three in Brazil and Research Institutes for Health Sciences, University of Chiang Mai, Chiang Mai, Thailand.  These sites were selected for their strong experience in clinical research; their capacity to involve their communities in carrying out this study; and their capacity to comply with all regulatory aspects of the study, including providing safeguards for participants.  These are not-for-profit organizations that have no financial ties to the drug manufacturer.

12. Why is this study being conducted in men who have sex with men (MSM)? 

This study is being conducted among MSM in Peru, Ecuador, the United States, South Africa and Brazil and Thailand because it is important to ensure that tenofovir/emtricitabine is safe and effective in those populations most in need of effective HIV prevention.  Conducting the study in a population that would be most likely to benefit from the research, 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 – including among intravenous drug users in Thailand and heterosexual men and women in Africa.

Study volunteers are active and informed participants and contributors to the study.  All volunteers undergo an intensive informed consent process that lays out the details of the study and its potential benefits and risks.  All study participants  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 free to leave the trial at any time without repercussions. 

13. Why is the study being conducted in Peru, Ecuador, the United States, South Africa, Brazil and Thailand?

Peru, Ecuador, the United States, South Africa, Brazil and Thailand were selected for this study because:

·      MSM in these countries are highly affected by the epidemic.  Studies indicate that prevalence of HIV infection in MSM is 10 percent or greater in these countries.

·      Site Investigators have an outstanding record of conducting HIV research.  All sites have demonstrated high levels of compliance with international clinical trial standards.

·      The governments of these countries have taken strong leadership roles in HIV prevention, and understand the importance of HIV research and how it can benefit their citizens.

·      It is essential that prevention research takes place where the epidemic is.

14. How has the community been involved in the study design and planning?

Consultation with 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 Community Advisory Board (CAB) comprising leaders of AIDS service organizations, community activists, and members of at-risk communities. 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. 

15. Is this study fully compliant with all ethical standards?

The study is fully compliant with the Declaration of Helsinki and all other ethical standards.

16. 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 IMPACTA in Peru, the University of San Francisco de Quito in Ecuador, the University of California San Francisco Committee on Human Research, Fenway, Cape Town University Institutional Review Board and the Fundacao Oswaldo Cruz Ethics Committe, ethic committes at the University of Sao Paulo, the Federal University of Rio de Janeiro and the University of Chiang Mai. These institutional review boards meet all applicable international standards.  The study was also reviewed and approved by the Ministries of Health of Peru, Ecuador and Thailand, the U.S. National Institutes of Health, the U.S. Food and Drug Administration, the Medical Research Council in South Africa and the Comissão Nacional de Ética em Pesquisa – CONEP in Brazil.

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 is 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 Peru, Ecuador, South Africa, Brazil and Thailand. The DSMB may recommend that a trial, or part of a trial, be discontinued if there are safety concerns, or if they believe that the trial objectives either have been achieved or cannot be achieved.

17. Do you need people to become infected to demonstrate whether PrEP helps to reduce the risk of acquiring HIV infection?

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 tenofovir/emtricitabine, it may mean that tenofovir/emtricitabine 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. 

18. 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, he is followed at the study clinic by infectious disease specialists with expertise in HIV care. The study provides 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.  Antiretroviral therapy is provided, if warranted, by the countries in which the study is being implemented.

19. Does tenofovir/emtricitabine have side effects?

While all HIV drugs have some side effects, tenofovir/emtricitabine 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 discontinued tenofovir/emtricitabine therapy because of side effects.  The most commonly reported side effects from use of tenofovir/emtricitabine are nausea, vomiting, diarrhea, and flatulence. These effects have largely been reversed after use of the drug was discontinued.  The study monitors the health of the participants very carefully, and discontinue the study drug if there is any sign of illness due to participation in the study.  Anyone who experiences any difficulty is monitored and cared for until the illness resolves.

20. 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 tenofovir/emtricitabine than to other HIV drugs.  In studies involving tenofovir, a component drug of tenofovir/emtricitabine, 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. 

21. 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 iPrEx study utilizes several safeguards 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 discontinued 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.

In the unlikely event that a study volunteer develops any resistance to tenofovir/emtricitabine, 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 tenofovir/emtricitabine.  

22. If tenofovir/emtricitabine prevents HIV infection in the study, will it be practical for broad use?  How will it be made available?

If tenofovir/emtricitabine is found to be highly effective at preventing infection with no serious side effects the 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 Ministries 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.

23. 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 are counseled that PrEP with tenofovir/emtricitabine 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.

Volunteers in other PrEP studies have reported decreases in the number of sexual partners and increases in 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.