CDC's Clinical Studies of Daily Oral Tenofovir for HIV Prevention

Research Rationale

• Why is CDC launching tenofovir HIV prevention trials?
• How would tenofovir work to protect against HIV infection?
• What data suggest that this approach may be safe and effective?

Why is CDC launching tenofovir HIV prevention trials?

CDC is sponsoring these trials because safe and effective new approaches to HIV prevention are urgently needed. Worldwide, an estimated 14,000 people continue to become infected every day (over 5 million per year). In the United States alone, an estimated 40,000 people become infected each year. Although behavior change programs have contributed to dramatic reductions in the number of annual infections in the United States and many other nations, far too many people remain at high risk.

With an effective vaccine years away, there is mounting evidence that antiretroviral agents may be able to play an important role in reducing the risk for transmission. Researchers believe that an HIV drug approved by the Food and Drug Administration -- tenofovir disoproxil fumarate (tenofovir, brand name Viread) -- taken daily as an oral preventive, is one of the most important new prevention approaches being investigated today.

If proven safe and effective, this approach could help address the urgent need for a female-controlled prevention method for women worldwide who are unable, because of cultural and other barriers, to negotiate condom use. Furthermore, if effective, tenofovir could provide an additional safety net for all men and women at risk due to sexual or drug-using behaviors, when combined with reducing the number of sexual partners, HIV counseling and testing, condom use, use of sterile syringes, and other prevention measures.

How would tenofovir work to protect against HIV infection?

The concept of providing a preventive before exposure to an infectious agent is not new. For example, travelers to an area where malaria is common are advised to take medication before and during travel to prevent the disease. The medicine to prevent illness is then already in their bloodstream if they are exposed to the malaria parasite.

Researchers believe that the same concept may work to protect people from HIV infection. Theoretically, if HIV replication can be inhibited from the moment the virus enters the body, it may not be able to establish a permanent infection.

What data suggest that this approach may be safe and effective?

Several sources of data suggest that an antiretroviral drug, taken regularly, may prove effective in reducing a person’s risk for infection:

• Providing a single dose of the antiretroviral drug nevirapine to HIV-infected women during labor and to their newborns immediately after birth has reduced the risk for mother-to-child transmission of HIV about 50%.
• In observational studies, the antiretroviral drug zidovudine, taken soon after exposure and continued for several weeks, has been associated with an 80% reduction in the risk of HIV infection among health care workers after needlesticks or other accidental exposures.
• Finally, animal studies have shown that tenofovir, administered before and immediately after a single retroviral exposure, can prevent the transmission of a virus similar to HIV in monkeys.

The safety and efficacy of tenofovir for the treatment of HIV infection has been well established in clinical studies and medical settings. The U.S. Food and Drug Administration licensed the drug for use as an HIV treatment in adults in October 2001, and over 150,000 HIV-infected patients around the world have now used the drug. Among these patients, tenofovir has resulted in a relatively low level of side effects and little development of drug resistance, compared to other HIV treatments. The most common side effects include nausea, vomiting, and loss of appetite.

One of the key objectives of these trials is to determine for certain whether the drug is safe and well tolerated by HIV-negative persons; and safety will be closely monitored throughout the trials. Researchers expect side effects to be even less common in the healthy, HIV-negative volunteers in these HIV prevention trials.