AIDS drugs may hold HIV prevention promise

Early research in rhesus monkeys indicates that a combination of two AIDS treatment drugs, tenofovir (TDF, Viread, Gilead; Foster City, CA) and emtricitabine (FTC, Emtriva; Gilead), may be effective in HIV prevention.1 Led by researchers from the Centers for Disease Control and Prevention (CDC), the findings may be the strongest animal data yet to suggest that the antiretroviral combination given before HIV exposure may prevent sexual HIV transmission.

Research of the drug combination is just one approach scientists are examining to stem the AIDS epidemic. The need for effective prevention tools is great: More than 5 million people worldwide are infected with the HIV virus each year; an estimated 40,000 Americans become infected on an annual basis, according to the CDC.2

There are currently three CDC trials designed to answer important questions about the safety and efficacy of pre-exposure prophylaxis (PREP) among populations at high risk for HIV infection, according to Terry Butler, CDC spokeswoman.

CDC has two studies of tenofovir PREP well under way, including a safety and efficacy trial among injection drug users in Thailand and an extended safety trial among men who have sex with men (MSM) in the United States, reports Butler. These studies will provide the first answers to whether with tenofovir alone is safe and effective in reducing HIV infection, she says.

The Thailand trial likely will produce the first data on the efficacy of PREP in humans, says Butler. Results may be available as soon as 12-18 months, she notes. Results from the U.S. trial will follow and provide data on the acceptability and behavioral safety of a daily PREP regimen in general, as well as the clinical safety of tenofovir among uninfected individuals.

Family Health International (FHI) of Research Triangle Park, NC, also is looking at the use of tenofovir in HIV prevention. Supported by a grant from the Bill & Melinda Gates Foundation of Seattle, researchers are looking at the drug's safety and effectiveness in preventing HIV infection in women from the West African country of Ghana who are at high risk of HIV infection.

The data analysis for the Ghana site was scheduled to be completed in mid-May, says Beth Robinson, deputy director for research dissemination at FHI. FHI is planning to share study findings in August at the Toronto International AIDS Conference, she reports.

Why test existing drugs?

Why look at existing AIDS drugs for HIV prevention? Research suggests that an antiretroviral drug, taken on a regular basis, may prove effective in reducing a person's risk for infection:

  • A single dose of nevirapine (Viramune, Boerhinger Ingelheim, Ingelheim, Germany) to HIV-infected women during labor and to their newborns immediately after birth has been shown to almost halve the risk for mother-to-child transmission of HIV.3
  • Zidovudine (Retrovir, GlaxoSmithKline, Research Triangle Park, NC), 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.4
  • 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.5

Combination eyed

Why is the CDC looking at a tenofovir-plus regimen using the TDF/FTC combination?

"There are now significant data suggesting the promise of both of these regimens [TDF alone, and TDF plus FTC] for different types of exposure," says Butler. "Because we don't yet know for sure how the animal data will correlate to human protection, we believe it is essential to move forward as quickly as possible to evaluate both of these extremely promising interventions."

The CDC is retooling plans for a Botswana, Africa trial designed to examine heterosexual HIV transmission to evaluate a tenofovir plus FTC regimen, says Butler. CDC researchers also are planning a safety study of the tenofovir plus FTC regimen in the United States. Study details have not yet been finalized, says Butler.

While the promise of PREP is enticing, public health officials do not see it as the only tool in the war against AIDS. The impact of PREP, if proven safe and effective, will be determined by how effectively it is combined with other strategies to provide the greatest protection. The CDC would not recommend it as a first-line defense against HIV, as no biomedical strategy is likely to be 100% effective, says Butler.

"PREP would need to be combined with reduction in sexual partners, HIV counseling and testing, consistent and correct condom use, and other prevention measures," Butler observes. "Even a high level of efficacy could be offset by increases in other risk behaviors, so it will be critical to guard against the abandonment of other, highly effective strategies."

References

  1. Garcia-Lerma J, Otten R, Qari S, et al. Prevention of Rectal SHIV Transmission in Macaques by Tenofovir/FTC Combination. Presented at the 13th Conference on Retroviruses and Opportunistic Infections. Denver; February 2006.
  2. Centers for Disease Control and Prevention. CDC's Clinical Studies of Daily Oral Tenofovir for HIV Prevention. Fact sheet. June 2005.
  3. Guay LA, Musoke P, Fleming T, et al. Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: HIVNET 012 randomised trial. Lancet 1999; 354:795-802.
  4. Cardo DM, Culver DH, Ciesielski CA, et al. A case-control study of HIV seroconversion in health care workers after percutaneous exposure. N Engl J Med 1997; 337:1,485-1,490.
  5. Otten RA, Smith DK, Adams DR, et al. Efficacy of postexposure prophylaxis after intravaginal exposure of pig-tailed macaques to a human-derived retrovirus (human immunodeficiency virus type 2). J Virol 2000; 74:9,771-9,775.