Friday, January 26, 2007

Pre-exposure Chemoprophylaxis

Leaders from around the world in AIDS research and health policy gathered in Toronto in August 2006 for the XVI International AIDS Conference. A key theme of the conference was HIV prevention, including assessment of old standards as well as new strategies. Leigh Peterson of Family Health International presented preliminary data from a current AIDS prevention study of women in Ghana (2006). This new prevention strategy is called pre-exposure chemoprophylaxis, or PrEP. In the PrEP strategy, HIV-negative individuals with high risk behavior take a single daily dose of tenofovir, a widely prescribed anti-retroviral. Tenofovir is a nucleotide reverse transcriptase inhibitor, meaning tenofovir’s unique shape blocks the reverse transcriptase protein in HIV from making new copies of the virus. The FDA approved tenofovir in 2001 and was a good drug candidate for this study because it has few side effects and showed low levels of resistance. The idea of prophylaxis is not new. It is most commonly used to prevent malaria; but it has not been tested as a valid strategy for preventing HIV until now.

According to the Family Health International study, 936 HIV-negative women in Ghana, Cameroon, and Nigeria were enrolled into a double-blind, 1:1 randomized trial. Half of the women received a daily 300 mg dose of tenofovir and the other half received a placebo. Between June 2004 and March 2005, participants were evaluated monthly for adverse events, abnormal serum creatinine and phosphorus levels, were HIV tested, and were re-supplied with drugs. Before the study was completed, the Nigerian trial was stopped due to faulty laboratory monitoring; and the Cameroon site prematurely closed due to ethical concerns about the study. The preliminary results presented at the AIDS conference showed that only two out of 363 women in the tenofovir group contracted HIV compared with six out of 368 in the placebo control group. While those in the PrEP group were 65% less likely to become infected, the difference was not statistically significant due to a small population size. There were no significant differences in adverse events or laboratory abnormalities between the two groups. Gilead, the maker of tenofovir, has committed to making the drug available at no profit cost to the areas where the need for prevention is greatest (Kresge 2003).

The Centers for Disease Control and Prevention is currently sponsoring three clinical trials of PrEP in homosexual men in San Francisco and Atlanta, men and women in Botswana, and intravenous drug users in Thailand (2006). These trials divide each subpopulation into two experimental groups: one taking tenofovir and the other taking truvada, a combination of tenofovir and emtricitabine. The results from these trials will not be available for at least another year.

Both of these PrEP trials attempt to answer the same questions: will prophylaxis reduce the risk of HIV transmission, is tenofovir a safe drug for uninfected individuals to take daily, and how will PrEP affect HIV risk behavior? PrEP is intended to be a part of an integrated approach to HIV prevention and should be used in concert with condoms, AIDS education and counseling, rather than by itself. If the PrEP strategy proves to be effective, then it could result in millions of averted AIDS deaths globally. One reason PrEP studies target women in Africa is because they are currently the most vulnerable and unprotected victims of AIDS. Specifically, PrEP would offer protection for women who are unable to negotiate condom use during sex and represents a big step toward empowerment of women in the third world. Important obstacles under consideration with PrEP are: the development of tenofovir-resistant HIV, increased risk behavior of people taking PrEP, and the cost effectiveness of using medication as a prevention strategy. Nonetheless, the discussion of an HIV prophylaxis at the international AIDS conference represents an expansion of HIV prevention strategies and the potential to avert future AIDS deaths.

Thanks for listening, I’m Wes Fiser


Centers for Disease Control and Prevention. CDC Trials of Pre-Exposure Prophylaxis for HIV Prevention: Clinical Trials in Botswana, Thailand, and the United States. August 2006.

Kresge, Kristen. Tenofovir as Pre-Exposure Prophylaxis. American Foundation for AIDS Research. February 2003.

Peterson, L et al. Findings from a double-blind, randomized, placebo-controlled trial of tenofovir disoproxil fumarate (TDF) for prevention of HIV infection in women. XVI International AIDS Conference, Toronto. August 13-18, 2006. Abstract THLB0103.

Friday, January 19, 2007

Considerations for Real-World Use of Microbicides

For more than ten years, the scientific community has been touting microbicides as the next big breakthrough in HIV/AIDS prevention. Microbicides are compounds that protect against sexually transmitted infections such as HIV and can be applied inside the vagina or rectum as a gel, cream, film, or suppository. Numerous strategies for microbicides are currently in development, including disruption of HIV’s viral envelope, maintenance of the normally acidic environment of the vagina, nonspecific inhibition of viral entry or fusion by creating a film over vaginal cells, and specific entry inhibition by providing competing ligands for receptors on CD4 cells. Despite the promise of various microbicides, results from efficacy trials will not be available for several more years. There are several areas of consideration when deciding which of the numerous microbicides in development will be realistic for real-world applications.
The first important factor to consider is the microbicide’s safety. Recent studies of nonoxynol-9 showed that the hopeful microbicide actually increased the risk of HIV infection. In vitro, N-9 disrupted the HIV envelope and prevented fusion. In vivo with prolonged use, however, the drug disrupted the vaginal epithelium, resulting in inflammation and a gathering of the immune cells. This aided HIV in overcoming the body’s natural defenses. This example shows that possible interactions with the body must be considered. Other safety issues should include complications from other sexually transmitted infections, drug resistance development in unknowingly infected women, and carcinogenicity of a compound continually applied to the vagina or rectum.
The next important real-world consideration is the acceptability of the microbicide. Many women will refuse to use something if it inhibits fertility. Thus, an effective microbicide should not also be a spermicide. In addition, the microbicide should be able to be applied well in advance of sex, in order to aid in secrecy of use if necessary. The microbicide should not be difficult to use or have an unusual consistency or smell. Finally, some countries in the world may not like microbicides based on genetically modified microorganisms.
One of the most important concerns is the efficacy of the microbicide. At the 2006 Microbicide Conference in South Africa, scientists began to push for drugs with higher potency towards HIV instead of drugs that are less effective but might prevent multiple sexually transmitted infections. In order to be truly effective, the microbicide would combine multiple methods of HIV prevention. A 2006 study by Robert Neurath found that some microbicides are extremely effective in vitro. However, development of these drugs did not take into account the nature of seminal plasma, a compound certain to be present in heterosexual intercourse. Neurath found that the plasma changed the pH environment significantly enough to alter the efficacy of the drug. This demonstrates just one of many possible interactions unaccounted for in current research and development.
The final factor in real-world use of microbicides is affordability. It is estimated that for microbicides to be available to donate to developing countries, each application must cost less than a dollar. Currently, only large pharmaceutical companies can afford the high cost of development of microbicides, which can cost up to tens of millions of dollars. Companies have little financial reason to develop these drugs when they are aimed primarily at poor women in developing countries. However, in 2003, the Bill and Melinda Gates Foundation pledged $60 million to aid with microbicide research aimed at HIV/AIDS, aiding the small laboratories struggling to develop these drugs. Ultimately, the investment will pay off. The World Health Organization estimates that a microbicide which only reduced the risk of infection by 40% and was only used in 30% of women in low-income countries would prevent approximately 6 million HIV infections in 3 years. This would reduce health care costs, not including the cost of antiretroviral drugs, by 3.2 billion US dollars.
More than 60 different microbicides are in development or testing currently. Not all of these, however, will meet the important criteria for real-world use. Even for those that do, data will not be available for several more years. The time and cost of development, however, is far outweighed by the hope that such a drug would give to the at-risk female population of the world.

This has been Cara Maguire.

Thursday, January 11, 2007

The AIDS Pandemic: A note to our listeners

Our podcast is now 6 months old. During this time, we have addressed many topics related to HIV/AIDS, including recent advances in treatment, the South African disability grant program, HIV in the Southeastern United States, and Bono’s Product (RED) campaign.

If you are a regular listener, you probably know that many of the episodes have been conceived, developed, and produced by Davidson College undergraduate students. Rebecca Jameson, a senior at Davidson, discussed violence toward women and the spread of HIV. Wes Fiser, another senior, talked about his personal experiences in Mwandi, Zambia.

Over the next several months, we will be posting additional episodes by these students on a weekly basis. I hope you stay tuned. If you have any questions about this podcast, please email me at If you would like to see other HIV/AIDS projects ongoing at Davidson College, please check my web site at