Female Condom Redesign, UN AIDS Denies Inflating Cases, Four-Drug Antiretroviral Regimen Eases Mother-Infant HIV Dilemma

Redesigning a Condom So Women Will Use It
Public health experts once held high hopes that the female condom would give women worldwide the ability to protect themselves from sexually transmitted diseases. But because of a range of problems-the device was perceived as awkward, unsightly, and noisy-it made little head-way with females other than sex workers. Six billion male condoms are delivered annually to developing countries compared with only 12 million female condoms.

Now a second-generation female condom has been developed by the Seattle-based nonprofit PATH (McNeil DG Jr. New York Times. November 13, 2007). It reportedly offers several advantages. It is inserted using a tampon-like bunched end instead of a stiff rubber ring. A softer, thinner polyurethane was used to better transmit warmth and provide a more natural feel. Adhesive dots on the outside cling to the vaginal walls, expanding with them during arousal. In testing among couples in Seattle, Thailand, Mexico, and South Africa, more than 90% liked the new device’s comfort and ease of use, and 98% rated its feel during sex as “OK to very satisfactory,” PATH said.

But PATH has encountered a major roadblock to bringing the new female condom to market. While the FDA designates male condoms as Class 2 medical devices, so that they must only pass tests for leakage and bursting, female condoms are designated Class 3. This puts them in the same category as pacemakers and heart valves, meaning that any new design must clear clinical trials at a cost of $3 million to $6 million. “That’s close to a 100% block, because no one’s willing to put up that sort of money,” said Dr Michael J. Free, PATH’s head of technology.

The original product was never able to fulfill the scientists’ goal of being a form of protection a woman could use without her male partner’s knowledge. This was the female condom’s biggest failure and one the redesign process could not correct. [CDC HIV/Hepatitis/STD/TB Prevention News Update, Tuesday, November 20, 2007]

UN Agency Denies Inflating Cases of HIV Deliberately
Following UNAIDS’s release of new, lower estimates of the number of global HIV infections, officials rebutted accusations that the agency had inflated estimates for years to secure more funding (McNeil DG Jr. New York Times. November 21, 2007). UNAIDS now estimates 33.2 million persons worldwide have HIV infection, down from its previous estimate of 39.5 million.

The accusation that UNAIDS deliberately inflated earlier estimates is “absurd,” Dr Paul De Lay, director of monitoring and policy at UNAIDS, replied at a news conference. The agency’s task is to give advice and monitor trends, and its budget does not come from international aid spent on AIDS drugs or vaccine research, he said. In addition, he stated, “cooking this data would be almost impossible,” because the data are assembled by health ministries in each country and overseen by several agencies.

The revised estimates stem from newer, more accurate data from India and several African countries and were gathered through expensive, time-consuming, household surveys. The earlier, higher estimates relied heavily on testing data from women attending urban health clinics.

It was not clear that the earlier estimates were probably too high until late 2003, said Dr Kevin M. De Cock, director of the Department of HIV/AIDS for the World Health Organization. The largest revision downward followed the July release of new data from India, he added.

A less noted aspect of the UNAIDS report is the longer life expectancy estimated for HIV-positive persons receiving no antiretroviral drugs. The past estimate of 9 years was based on a Ugandan study conducted in the 1990s; the new estimate has increased to 11 years based on findings from several studies that will soon be published, said Dr Peter Ghys, chief of epidemiology at UNAIDS. The impact of this revision was to lower assumptions about how many persons were infected each year, Ghys said. UNAIDS concluded that new infections peaked between 1997 and 2001. However, this revision did not radically change the estimated scale of the global epidemic, he said. [CDC HIV/Hepatitis/STD/TB Prevention News Update, Wednesday, November 21, 2007]

HIV Vaccine Trial Volunteers May Face Social Blow
A new study finds that many participants in experimental HIV vaccine trials report negative social impacts because of their involvement (Boggs W. Reuters. November 29, 2007).

Dr Jonathan Fuchs of the San Francisco Department of Public Health and colleagues studied 5417 mostly male volunteers in an HIV vaccine efficacy trial. Of these, almost 1000 reported negative social consequences during the 36-month follow-up. Most of these were attributed to family, friends, and partners, the researchers found. These negative reactions were primarily related to a misunderstanding of the trial participant’s HIV status or risk of infection.

Fewer than 1% of volunteers reported problems with health, disability, life insurance, employment, medical or dental care, government agencies, or housing, said the researchers.

The study found that of the 368 participants who became HIV-infected after enrollment in the trial, only 12 reported a negative social incident. Most incidents involved personal relationships, such as family or friends asserting that the vaccine caused the infection or made the participant more susceptible to HIV infection. “Since a majority of the negative social impact events were due to negative reactions from friends and family who misinterpreted what a preventive HIV vaccine trial entails,” said Fuchs, “trial sites need to continue their educational efforts with study participants and with local communities, emphasizing that you cannot become HIV-infected from the vaccine itself and that these trials seek HIV-negative individuals to participate.”

“A substantial proportion of vaccines may test ‘false-positive’ on a standard HIV antibody screening test,” continued Fuchs. “Providers should remember to first ask whether their patients have participated in an HIV vaccine trial before they perform HIV testing, to avoid potential misinterpretation of antibody results and possible social harm.”

The study, “Negative Social Impacts Among Volunteers in an HIV Vaccine Efficacy Trial,” was published in the Journal of Acquired Immune Deficiency Syndromes (2007;46:362-368). [CDC HIV/Hepatitis/STD/TB Prevention News Update, Friday, December 7, 2007]

New Drug Combo Eases Mother-Infant HIV Dilemma
A study of HIV-infected pregnant women given a new drug combination of NNRTIs during labor found they were about half as likely to develop resistance to that class of drugs 6 weeks after delivery as was a second group given fewer AIDS drugs (Agence France Presse. November 7, 2007).

A single dose of the NNRTI nevirapine during labor reduces a mother’s chance of infecting her infant by 40%. However, if the newborn does become infected, the baby is far more likely to acquire a strain of the virus that is resistant to common HIV drugs. There is also an increased chance the same resistant virus will develop in the already infected mother.

Benjamin Chi of the Center for Infectious Disease Research and the University of AlabamaBirmingham and colleagues studied 397 HIV-infected pregnant women seeking care at 2 public health facilities in Lusaka, Zambia. Those in the first group, about half (199) of the mothers-to-be, were given single doses of tenofovir and emtricitabine, both NRTIs, along with nevirapine during childbirth. Those in the second group (198) were given nevirapine, as is the standard practice. Both groups also received a short course of zidovudine.

The researchers determined that 6 weeks postdelivery, the women given the 4-drug combination were 53% less likely to develop higher resistance to NNRTIs. The absolute risk was cut in half: 12% for the test group, and 25% for the control group. Some serious adverse events were reported-postpartum anemia for mothers, pneumonia for infants-in both groups, although none was judged to be caused by the 4-drug combination.

The study’s results “provide strong evidence that adding single-dose tenofovir/emtricitabine” to the standard treatment “is a new, effective, and feasible approach to reducing maternal nevirapine resistance,” Shahin Lockman and James McIntyre of the Harvard School of Public Health said in a related commentary.

The study, “Single-Dose Tenofovir and Emtricitabine for Reduction of Viral Resistance to Non-Nucleoside Reverse Transcriptase Inhibitor Drugs in Women Given Intrapartum Nevirapine for Perinatal HIV Prevention: An Open-Label Randomized Trial,” and the commentary, “Reduction of HIV-1 Drug Resistance After Intrapartum Single-Dose Nevirapine,” were published in The Lancet (2007;370:1698-1705 and 1668-1670, respectively). [CDC HIV/Hepatitis/STD/TB Prevention News Update, Monday, December 10, 2007]

Semen Protein Could Be a Key in AIDS Battle
In a new finding, German scientists have identified a protein in semen that boosts the infectious potential of the virus by 100,000-fold, which may explain how HIV spreads through sexual contact and also may offer a strategy for stopping it. The discovery came about when researchers at the University of Ulm were screening molecules from semen samples in the hope of finding some that might naturally block HIV. Instead, they found protein fragments that promote HIV infection by grouping together to ferry viral particles to cell surfaces (Russell S. San Francisco Chronicle. December 14, 2007).

“This is one of the most interesting new perspectives on HIV transmission to emerge in years,” said Dr Warner Greene, director of the Gladstone Institute of Virology and Immunology in San Francisco. The new findings, he said, may answer a question that has long perplexed researchers: why a virus that is weakly infectious in the laboratory can spread so efficiently through sexual contact. Scientists have found it takes 1000 to 100,000 HIV particles to create a successful infection in the laboratory. But when the newly identified proteins are added, a successful infection can result from as few as 3 virus particles.

This knowledge, in turn, raises the possibility that blocking the molecule-dubbed semen-derived enhancer of virus infection, or SEVI-could make it much harder for HIV to spread. Studies now might be conducted to see how prevalent the protein is among at-risk populations, said Dr Jay Levy, a virologist at the University of California, San Francisco, and one of the first scientists to isolate HIV. For instance, semen from HIV-infected men whose partners remain uninfected despite having unprotected sex might be analyzed to see whether the protein is present or is somehow blocked.

The full report, “Semen-Derived Amyloid Fibrils Drastically Enhance HIV Infection,” was published in Cell (2007;131:1059-1071). [CDC HIV/Hepatitis/STD/TB Prevention News Update, Wednesday, December 19, 2007]

“Best-Kept Secret” for HIV-Free Africa
Increasingly, researchers are looking into whether pediatric HIV prevention efforts should shift from treating mothers and their newborn babies to a less expensive and easier alternative: birth control.

Despite sustained political and financial support for programs to reduce mother-to-child HIV transmission, studies indicate that just 1 in 10 infected African mothers has access to the antiretrovirals that can cut the risk of infection during labor by more than half (Timberg C. Washington Post. December 16, 2007).

UN estimates released last month show that of the 2.5 million children with HIV worldwide, almost 90% live in sub-Saharan Africa. The overwhelming majority of these were infected through their mothers. Raising these children, most of whom will die young after long periods of illness, is difficult, especially for a mother who is also infected. According to the non-governmental group Family Health International (FHI), providing antiretroviral treatment to pregnant women prevented 101,000 cases of pediatric HIV infection between 1999 and 2006. Contraception, meanwhile, averts the births of 173,000 HIV-infected babies every year. Surveys indicate that most HIV-infected women do not want to become pregnant again for fear of infecting their babies and leaving their healthy offspring as orphans.

“It tends to be the best-kept secret in HIV prevention,” said Ward Cates, head of research at FHI, which has extensive experience in Africa. Yet, international funding of birth control programs has declined. US support of family planning began to wane in 1996, after Republicans assumed control of Congress. European donors also shifted money away from contraception and toward other programs.

When the President’s Emergency Plan for AIDS Relief (PEPFAR) was created in 2003, some administration scientists lobbied for expanded family planning efforts, but their advice was vetoed by top program officials. PEPFAR does pay for condoms, but surveys show that Africans rarely use them for contraception. Program officials say they do not object to family planning but opt to focus funding on initiatives they regard as directly related to HIV/AIDS. [CDC HIV/Hepatitis/STD/TB Prevention News Update, Thursday, December 18, 2007]