Enrollment Set to Begin in Studies of Tenofovir as Vaccine to Prevent HIV Infection

By Ronald Baker, PhD

Enrollment will start soon for a pivotal study in 400 San Francisco and Atlanta gay men of the antiretroviral drug tenofovir (Viread) as a vaccine to prevent HIV infection.

Tenofovir is a nucleotide analog anti-HIV drug developed by Gilead Sciences of Foster City, CA. Tenofovir is currently FDA-approved for the treatment of chronic HIV infection in combination with other antiretroviral drugs. The drug also shows potent anti-hepatitis B activity.

In part due to tenofovir’s potency against HIV, its ease of administration as a once daily medication and its relatively favorable toxicity and resistance profiles, vaccine researchers have chosen to test the drug as an HIV vaccine candidate. It is hoped that the anti-HIV effect of tenofovir will keep the virus from infecting blood cells in healthy (non HIV-infected) humans who are exposed to the virus.

"There are 150,000 HIV-infected people who have been on tenofovir, and the safety profile looks very good," said Dr. Lynn Paxton, who is coordinating the American and overseas studies of tenofovir for the US Centers for Disease Control and Prevention in Atlanta. "We want to look at it, to see if it is safe for HIV-negative people.''

Objectives

In addition to the study group planned for San Francisco, another arm of the vaccine study will take place in Atlanta, GA. The primary objectives of the study are (1) to evaluate the safety of tenofovir as a preventive vaccine among gay men and (2) to determine if its use is likely to encourage unsafe sexual practices that would increase the rate of HIV infection among gay men; and (3) to discover the number of gay men who may become infected with tenofovir-resistant HIV.

Methods

The researchers will select two hundred gay men in Atlanta and San Francisco as study participants who will be randomized to take tenofovir or a placebo (an inactive substance) once daily for two years. The study will be blinded, with neither the participants nor the investigators aware of who is taking tenofovir or who is taking placebo. At the end of the two-year period the study will be unblinded and the outcomes in the two groups will be compared. Under certain circumstances, the two studies could be stopped early.

Because of their relatively small size, the Atlanta and San Francisco study arm will not yield sufficient data to determine if tenofovir can prevent HIV infection in HIV negative gay men. A large trial with a design similar to the two US studies has begun in Africa with study sites in Cameroon, Ghana and Nigeria. The US Centers for Disease Control and Prevention has also initiated tenofovir vaccine trials in Thailand and in Botswana. These studies are among heterosexuals—1200 HIV negative men and women in Botswana and 1,600 HIV negative IV drug users in Bangkok.

Ethical Issues of Vaccine Research

In order to demonstrate conclusively that a preventive vaccine will work to prevent HIV infection in a significant percentage of individuals, the investigators must find that the participants taking the placebo experience a significantly higher infection rate than those taking the study drug (in this case, tenofovir). At the same time, the researchers have an ethical duty to do everything possible to keep all the study participants from practicing behaviors that can lead to infection with HIV (e.g., unprotected anal and vaginal intercourse, use of “dirty” needles).

In short, the investigators must ensure that the study participants are well informed about safe and unsafe behaviors so that their risk of infection will remain as low as possible.

Susan Buchbinder, MD, head of HIV research at the SF Department of Public and a principal investigator of the San Francisco study, noted that although it is possible for all the study participants to remain HIV negative throughout the two-year term of the study. However, decades of vaccine research have shown conclusively that no matter how well-educated about infection risks participants become, a certain percentage of those who are at the highest risk for infection (such as gay men in San Francisco in Atlanta) will become HIV-infected (approx 2-4 percent, historically).

Another concern for the researchers and for some AIDS activists is that if the study results demonstrate that tenofovir can protect against HIV infection to some significant degree, a number of individuals at higher risk for infection (such as gay men in Atlanta or San Francisco) may not be motivated to practice safe sex, in the belief that the drug offers them enough protection to warrant practicing higher risk activities.

According to Dr. Buchbinder, the studies in San Francisco and Atlanta have been purposefully designed to detect this possible outcome among the gay male participants, as well as to show if this outcome would outweigh any benefit from the use of tenofovir as a preventive vaccine in populations at higher risk for HIV infection.

Study Volunteers

If you are interested in volunteering for one of the tenofovir studies in San Francisco or Atlanta, visit the SF Department of Public Health AIDS Office website at www.sfaidsresearch.org. Information about enrollment is expected to be posted on this website soon.

12/03/04

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