15 JULY 2011, VOLUME 12, ISSUE 28

A new study has added to growing evidence that a daily dose of antiretroviral treatment taken by the HIV-negative partner in a heterosexual, HIV-discordant relationship can significantly reduce the risk of HIV transmission. The Partners PrEP trial, the largest to date to consider the effectiveness of pre-exposure prophylaxis (PrEP) for HIV prevention, involved 4,758 HIV-negative people in Kenya and Uganda, all with HIV-positive partners. One-third of HIV-negative participants took a daily tablet of the antiretroviral, tenofovir; one-third a combination of tenofovir and emtricitabine; and the rest a placebo. The trial, begun in July 2008 and conducted by the University of Washington's International Clinical Research Centre, ended a year early due to the overwhelming evidence produced. "We found that the people [taking] tenofovir... had an average of 62 percent fewer HIV infections than those [taking] the placebo... while participants [on] the combination... had 73 percent fewer infections than those [on] the placebo," Jared Baeten, lead investigator of the trial and assistant professor of global health and medicine at the University of Washington, told IRIN/PlusNews...

A second study conducted by the US Centers for Disease Control released similar results on 13 July. Named TDF2, it involved 1,200 heterosexual men and women in Botswana and found that 62.6 percent fewer HIV infections had occurred in participants taking a combination of tenofovir and emtricitabine compared with the placebo group. "These results show that it is time for national governments to evaluate and incorporate PrEP into HIV policy," said Baeten... Nelly Mugo, one of the study's Kenyan investigators, said moving PrEP from research to policy needed to be handled carefully. "The challenge is to find the people most at risk; it's not like iodine in salt - ARVs are not for everyone," she told IRIN/PlusNews. "NASCOP [Kenya's National AIDS and Sexually transmitted infections Control Programme] needs to think keenly about how to find and target people at risk without creating stigma." Mugo further emphasized that for treatment as prevention and PrEP to work, it would be imperative for more people to be tested for HIV. "Currently, [fewer] than 60 percent of Kenyans know their HIV status; those numbers have to go up in order to know who is HIV-positive and needs to start on ARVs earlier and who is HIV-negative but at high risk and needs to start taking PrEP," she said. "Overall, the findings are very exciting and PrEP is a wonderful package, but it needs to be rolled out with care."...

UNAIDS and the UN World Health Organization have hailed the results of the Partners PrEP and the TDF2 study, with Michel Sidibe, executive director of UNAIDS, saying the studies could "help us to reach the tipping point in the HIV epidemic". UNAIDS and the World Health Organization have already been working with countries in sub-Saharan Africa, Latin America and Asia to explore the potential role of PrEP in HIV prevention. "In Kenya and Tanzania we have held regional stakeholders' meetings to discuss the potential role of PrEP should the results of these trials be positive," Kate Hankins, chief scientific adviser to UNAIDS, told IRIN/PlusNews. "In Kenya in particular, we will now be looking at where and how we can use PrEP; whether to integrate it with male circumcision, or to use it in PMTCT with HIV-negative male partners of pregnant women... it will take some thinking."

According to 2008 data published by the Centers for Disease Control and Prevention (CDC), there were approximately 56,300 new HIV infections in the United States in 2006. That number has remained relatively steady since the late '90s, and has actually increased overall since the early '90s, when new infections reached a low of around 50,000 per year. "It's such a striking statistic," said Dr. Roy Gulick, (director of the Weill Cornell Medical College HIV Clinical Trials Unit). "To a lot of people, it means that HIV prevention efforts have not been working. In particular, the group we've seen a significant increase in recent years has been young gay men. So it's become clear that we need new and specific strategies to help them prevent themselves from being infected." The promising future sought by so many medical professionals who are combating the AIDS epidemic may lie in the research and development of pre-exposure prophylaxis (PrEP). An outgrowth of post-exposure prophylaxis (or PEP, a short-term antiretroviral treatment that has been used since the early '90s to decrease the likelihood of HIV infection after exposure to the virus, either occupationally or through sex), PrEP is a similar antiretroviral "drug cocktail" that could be taken (and in some cases, already is being taken) by HIV-negative men in order to help prevent them from becoming infected (seroconverting)...

A group of physicians is urging the Food and Drug Administration not to approve a drug made by Gilead Sciences for the prevention of HIV infection. Fifty-five physicians signed a letter spearheaded by the AIDS Healthcare Foundation citing concerns about the use of Gilead's Truvada (tenofovir disoproxil fumarate and emtricitabine) for "pre-exposure prophylaxis," or PrEP. Concerns included the risk of a decrease in condom use and a lack of information showing proper use in "real world" situations. "As medical care providers, we strongly support continued research on the prevention of HIV, but oppose approval of a pre-exposure prophylaxis that runs the risk of contributing to the spread of HIV and drug-resistant viruses," the physicians wrote. "Our first obligation is to do no harm to individuals and to the public health."

Merck & Co. (MRK) said it will join projects led by two major U.S. universities to develop new approaches toward eradicating HIV, the virus that causes AIDS. The collaboration is the latest in a string of partnerships between drug firms and academia, including Gilead Sciences Inc.'s (GILD) four-year cancer-therapy project with the Yale School of Medicine. Merck will join a new project led by the University of North Carolina Chapel Hill that will look for ways to purge persistent infection of the virus from the body. The research team includes 19 investigators from UNC and eight other U.S. universities. Merck is the project's only pharmaceutical industry partner. At the same time, Merck will work with researchers at the University of California San Francisco on a five-year project to define HIV's reservoirs, better understand the reservoirs and test potential treatments for the virus. "Collaboration has been the hallmark of much of the progress made against HIV since the virus was first identified 30 years ago," Merck Research Laboratories Vice President Daria Hazuda said. "Merck is honored and excited to participate in these important new undertakings." The National Institute of Allergy and Infectious Diseases, a part of the National Institutes of Health, will fund most of both research efforts. Merck will not receive any funding for participating in the projects.

Altering an HIV-infected person's stem cells not just to combat the virus that causes AIDS, but to eradicate it was -- to many researchers -- a pipe dream. Even the idea of a cure, while in the forefront of their minds, was thought improbable. But a cure is exactly what Seattle's Fred Hutchinson Cancer Research Center will be pursuing with a $20 million, five-year research grant announced Monday by the National Institutes of Health. "The field is now addressing the possibility of developing a cure, it was an abstract notion," said Hans-Peter Kiem, an expert in stem-cell transplantation and one of two principal investigators for this project. "To receive the resources to move this work forward is very exciting." Two other research institutions received similar grants: the University of California, San Francisco, and the University of North Carolina, Chapel Hill.

The team of scientists at "The Hutch," in partnership with Sangamon Biosciences, a biopharmaceutical company based in Richmond, Calif., will be investigating a two-pronged approach aimed at eliminating HIV infection from the body. Led by Kiem and his colleague, Keith Jerome, an expert in viral infections, the team will focus on ways of overcoming a major challenge to long-term control and a cure for the virus: existing HIV reservoirs, bits of genetic material that remains dormant in cells and tissue throughout the bodies of infected persons. ... The scientists plan to take an infected person's cells and make them HIV-resistant by eliminating a receptor on the surface of immune system cells that acts as a trap door for the virus to enter. This modification is meant to emulate a rare genetic mutation found in a remarkably small percentage of the population. Those modified cells are then reintroduced into the body, in a process similar to a bone-marrow transplant... The second prong of the Hutch team's approach is to attack the virus head-on, by developing proteins to attack the viral reservoirs that sleep in places like the liver or brain, without harming the infected cells themselves. This attack plan is meant to complement the stem-cell transplants that would have already made the remaining cells immune to re-infection. The end-goal to the project is to better understand how to modify stem cells and to successfully attack the virus, streamlining the process along the way. "We really have many of the pieces of the puzzle here," said Kiem. "We have the ability to modify stem cells and transplants, ways of fighting the virus and hopefully a way to provide something meaningful to patients." If all goes according to plan, human clinical trials are expected to begin in five years.

Every time Bijaya Dhakal goes out to meet people and tell them what she does for a living, the simple task becomes an act of courage requiring nerves of steel. Dhakal is the founder of Nepal's first and only organisation of women sex workers now trying to make the state and society listen to a community long hushed by poverty and discrimination. A widow who had not completed school, the 35-year-old mother of two became a sex worker after struggling to raise her family on the meagre wages she earned in a factory. For almost eight years, she led a double life, working in the capital Kathmandu and returning to her village sporadically, with her family believing she worked for a non-government organisation. "Sex workers suffer at the hands of the police and, at times, their customers who beat them up or rob them. Yet they can't complain because the moment people learn what they do, a change comes over them," Dhakal says. "Landlords throw them out, and even doctors and nurses at the hospitals loathe touching them for fear of contracting some disease. I began to wonder one day, how long can we stay hidden? If we continue to hide, how will our needs and demands be met?"

Six years ago, Nepal's growing gay rights movement inspired Dhakal to cast aside the veil of anonymity and start Jagriti Mahila Sangh. Jagriti means awakening, and Dhakal hopes it will catalyse sex workers hidden in the 75 districts of Nepal to unite for a change in their lives. "I saw all these male sex workers, transgenders, and people living with HIV/AIDS declaring their status in public and demanding their right to be treated like any other citizen," she says, sitting in Jagriti's office in Kathmandu, a three-room apartment that did not have a single stick of furniture when it opened with seven registered members. "They gave me courage. Besides, I was tired of speaking through intermediaries who often failed to convey correctly to the state authorities and donors what we wanted," she added. Today, Jagriti Mahila Sangh has grown into Jagriti Mahila Mahasangh, a federation with 26 associates spanning 23 districts, mostly in eastern Nepal and the southern Terai plains bordering India. Its major donors are the U.N. Development Programme, the British government's Department for International Development, and Save the Children. Dhakal feels even the donors are uneasy. "They prefer working with the HIV/AIDS community over us," she says. "They think, being uneducated, we won't be able to manage our projects and also, what we do for a living puts them off."

Nepal's sex workers have a chance to be heard, with the parliament writing a new constitution slated for promulgation by Aug. 28. But Jagriti fears sex workers will be excluded from the new charter....Besides rights activists, Nepal's health experts are also urging the government to sensitise the police, especially in view of the rising incidence of HIV/AIDS. According to Nepal's state-run National Centre for AIDS and STD Control (NCASC), the estimated number of HIV positive people as of 2009 was a little over 63,500. Women formed 28.6 percent, out of which 605 -- about one percent - were sex workers. Every year, an average of over 4,700 new infections are reported, with about the same number of deaths. The government has just conducted a new survey which puts the number of known commercial sex workers at 28,000. "The HIV figures are just the tip of the iceberg," says NCASC director Dr Krishna Kumar Rai. "These are the people who came forward for treatment or condoms and so their status was known. But it is likely there is a large group which has not come forward. Police raids will only serve to drive HIV positive sex workers underground. And then it will be impossible to trace or treat them."

The executive director of UNAIDS warned Monday that critics who say China is too wealthy to be receiving donations for fighting HIV are off the mark. "I think it'll be a big mistake for a donor and particularly, for anyone who's invested in China today, to withdraw, for the simple reason that this funding is a catalytic fund," Michel Sidibe said in Beijing at a meeting of health ministers from Brazil, Russia, India, China, and South Africa. By creating linkages among government, civil society, and nongovernmental organizations (NGOs), the Global Fund to Fight AIDS, TB and Malaria is making progress in China, Sidibe said. The fund has approved $947 million to China, of which $369 million goes toward HIV/AIDS. China has cracked down on AIDS activists and NGOs working there, yet it also has launched programs to provide universal access to antiretroviral treatment and introduced policies to curb disease-related discrimination. In June, officials released Hu Jia, a longtime advocate for rural HIV/AIDS patients, after he served three-and-a-half years in jail on subversion charges. Sidibe said Vice Premier Li Keqiang told him Monday that involving community-based organizations in the fight against AIDS "was an important transformation that China wants to see."

Civil society in Kenya is considering various ways of sustaining and expanding antiretroviral treatment (ART) programs, including a tax on cellphone users. Currently, donors provide more than 90 percent of the funds used to supply ART to Kenyans. The Japanese government, a major donor to the Global Fund to Fight AIDS, TB and Malaria, announced two months ago it intends to scale back its contribution following the recent earthquake and tsunami. Pediatric HIV treatment and efforts to prevent mother-to-child transmission are funded solely by the US President's Emergency Plan for AIDS Relief. James Kamau of the nongovernmental group Kenya Treatment Access Movement said cellphone taxes are being considered because nearly all other sectors are overtaxed. "What we are asking for is a 10 Kenyan-cent (US $0.001) levy for every phone call made from the country," he said. "If the proposal finds favor among the lawmakers, then the funds raised from such levies will go a long way to scale up the number of Kenyans living with HIV/AIDS who need to be enrolled [in ART], and sustain treatment in case the donors pull out or reduce funding," explained Kamau. In Kenya, an estimated 1.4 million people are living with HIV and of these, 760,000 have fully developed AIDS. Just 343,000 Kenyans with HIV/AIDS can currently access ART.

A new global survey of more than 5,000 men who have sex with men (MSM) reveals a marginalized group of people with little access to basic HIV prevention tools such as condoms and few means to learn about HIV. Conducted by the Global Forum on MSM & HIV between 24 June and 17 August 2010, the survey sought to highlight key gaps in global efforts to provide MSM with evidence-informed HIV prevention services. More than 1,000 of the study participants - drawn from all over the world - were health workers; 22 percent reported being HIV-positive. The authors recommend expanding access to HIV prevention services for MSM across the globe, more focus on promoting awareness of emerging HIV prevention interventions and more robust and sustained stigma-reduction efforts. Some of the major findings of the survey include:

Access to health services - Fifty-three percent of participants said they could easily access testing for sexually transmitted infections, while 51 percent said they had easy access to HIV counselling; 47 percent found STI treatment easily accessible. Just 36 percent of MSM surveyed reported having easy access to HIV treatment, while 27 percent said it was available but difficult to access, was not available or had never heard of HIV treatment.

Access to HIV prevention - Free condoms were easily accessible only to 44 percent of participants, while just 29 percent could obtain lubricant. Just 30 percent of participants reported easy access to each of the basic HIV prevention services, including behavioural HIV/AIDS interventions, HIV education materials, mental health services, free or low-cost medical care, media campaigns focused on reducing HIV, and laws/policies to ensure access to HIV prevention. Just 25 percent said they had access to sex education.

Stigma - Africa reported the highest levels of stigma and external homophobia, followed by the Middle East, Asia-Pacific, Central/South America and the Caribbean, which all reported similar levels of stigma. Australia and New Zealand reported the lowest levels of stigma and external homophobia. MSM from Africa and the Asia-Pacific region reported the highest levels of internalized homophobia.

MSM-specific services - Some 52 percent of respondents reported that MSM health facilities were not available or unknown. Media campaigns to reduce homophobia were rare, with 30 percent of the survey's participants reporting that anti-homophobia campaigns were not available and another 20 percent saying they were "unheard of".

Knowledge of and access to emerging HIV prevention strategies - Fifty percent of respondents said medical male circumcision was easily accessible and just 10 percent had not heard of circumcision as a biomedical strategy for HIV prevention. Post-exposure prophylaxis (PEP) was described as easily accessible by only 18 percent of respondents, with 35 percent reporting that they had never heard of PEP. Thirty-nine percent of participants had never heard of pre-exposure prophylaxis for HIV prevention, while 44 percent of MSM had never heard of topical microbicides.

The National Minority AIDS Council (NMAC) recently launched a new website to help increase awareness about the funding crises affecting state AIDS Drug Assistance Programs across the country. More than a dozen ADAPs have created waiting lists for potential new clients, while 17 more have adopted various other cost-containment measures in the long wake of the recession. As of July 7, 8,655 people with HIV/AIDS were on waiting lists for ADAP assistance in 13 states, according to the National Alliance of State & Territorial AIDS Directors. Part of NMAC's "ADAP Beyond the Numbers" campaign, the new website features a collection of videos made by some of the people who rely on ADAPs to receive their medications. NMAC is encouraging people to submit their own clips. According to the Office of Minority Health, racial and ethnic minorities accounted for almost 71 percent of new HIV/AIDS diagnoses in 2008. African Americans represented 52 percent of new HIV/AIDS diagnoses that year. In 2009 in Florida, one in 42 black males, one in 63 black females and one in 113 Hispanic males were HIV-infected, according to state Department of Health data. Florida's ADAP waiting list of 3,513 people is the nation's longest.

With the knowledge that people age 45 and older represent the fastest-growing STD population, New Mexico health experts are urging residents to take steps to prevent infection. "Sexual health is everyone's responsibility," said Tara Misra, health educator for the University of New Mexico (UNM). People need to educate themselves about STDs, become familiar with their bodies and use protection, she said. It also is recommended that "people get into a pretty regular habit of being tested," particularly when starting new relationships, Misra said. Dr. Joel Teicher, an obstetrician/ gynecologist at ABQ Health Partners, said late-life divorce and post-divorce dating are factors driving STDs in older people. Chlamydia, a bacterial infection that often shows no symptoms, is "far and away the most-common" STD he sees. "STDs are equal opportunity infectors," said Dr. Peggy Spencer of UNM's Student Health and Counseling. "The germs don't know how old you are. Anyone who has sex can get an STD. It's more about your behavior than your age. If you have unprotected sex at any age you might catch something."

In a policy statement issued Wednesday, the Obama administration voiced its opposition to a House appropriations bill that would bar the District of Columbia from using local taxpayer dollars to fund needle-exchange programs [NEPs] and abortions for poor women. The restrictions undermine D.C. home rule, the administration said. The statement said Congress should not ban the use of federal funds for NEPs in the District, since such funding is allowed elsewhere when local officials decide the programs are effective. The president did not, however, threaten to veto the spending bill over the issues.

The strategy if approved by relevant authorities will reduce the risks of HIV infection among discordant couples and heterosexuals by between 63 percent and 73 percent. Kenyan researchers in collaboration with the International Clinical Research Center, University of Washington (U.S.A) have successfully developed drugs that if well administered can prevent an HIV negative person from getting infected. The pills Tenofovir and FTC which is a combination of Tenofovir and emtricitabine were under research from July 2008 to November 2010. Speaking during the launch of the research findings Thursday, Doctors Nelly Mugo and James Kiarie who were among the chief investigators said the drugs were taken daily by the participants as preventive therapy. However, researchers say the drug is not a 100 percent effective and have appealed to Kenyans to observe safe sexual practices. The pre exposure prophylaxis study involved 4,758 sexually active HIV discordant couples this being the largest risk group accounting for over 60% of new infections in Africa. They were enrolled in 9 clinical sites in Uganda and Kenya where the partners who were not infected were put under 3 groups of medication. One group was under Tenofovir, another group took emtricitabine/tenofovir while the third took placebo which is an inactive tablet that contains no medicine. The uninfected participants were tested every month for HIV and until May this year, 78 of them were infected, 13 under TDF, 18 under the combination of TDF/FTC while 47 were those assigned to placebo which was stopped today. The first group had an average of 62% fewer infections while the 2nd group has 73% fewer infections. The combination regime of ARVs suggests that a couple in which one partner is HIV positive stand to live a fulfilling life and bear children without infecting the entire family. Researchers are hoping that this breakthrough will inspire the search for an ultimate vaccine to prevent HIV infections in future.

The partners of people who have HIV can protect themselves from infection by taking a once-daily pill, two groundbreaking studies in Botswana, Kenya and Uganda have shown. The discovery could bring work to combat Aids close to a "tipping point", experts say. Attempts to promote condom use to protect against HIV in the hardest-hit parts of the world, and particularly Africa, have hit cultural barriers and had limited success. But now it appears that men or women who know -- or suspect -- their partner has HIV could protect themselves, secretly if necessary. The larger study, involving 4,758 "discordant" couples (where one has HIV but the other has not) in Kenya and Uganda, led by the University of Washington's International Clinical Research Centre, shows that those taking a single daily tablet of the Aids drug tenofovir had 62% fewer infections and those who took a pill combining tenofovir and emtricitabine had 73% fewer infections than those who took a placebo pill. The drugs have few side-effects, which is important if they are to be given to healthy individuals. Both are made by Gilead, which has licensed their manufacture to generic companies in the developing world, allowing them to produce cheap copies -- so this is a relatively inexpensive intervention. "This study demonstrates that antiretrovirals are a highly potent and fundamental cornerstone for HIV prevention and should become an integral part of global efforts for HIV prevention," said Dr Connie Celum, professor of global health and medicine at the university and principal investigator of the study, known as the Partners PrEP Study, which was funded by the Bill and Melinda Gates Foundation.

The second study in Botswana was conducted by the United States Centres for Disease Control. It followed 1,200 heterosexual men and women without HIV who received either a once-daily tenofovir/emtricitabine tablet or a placebo pill. The antiretroviral tablet reduced the risk of acquiring HIV infection by roughly 63% overall. "This is a major scientific breakthrough which re-confirms the essential role that antiretroviral medicine has to play in the Aids response," said Michel Sidibe, Executive Director of the Joint United Nations Programme on HIV/AIDS (UNAIDS). "These studies could help us to reach the tipping point in the HIV epidemic."

The news follows hard on the heels of another very significant finding -- that people with HIV who are taking combinations of antiretroviral drugs not only stay healthy themselves but are unlikely to infect their partner. The two pieces of research give a massive boost to the cause of rolling out more Aids drugs and treating people at the earliest stage of their illness. "Effective new HIV prevention tools are urgently needed, and these studies could have enormous impact in preventing heterosexual transmission," said Dr Margaret Chan, WHO's director general. "WHO will be working with countries to use the new findings to protect more men and women from HIV infection."

More than 140 scientific societies and universities has sent a letter urging U.S. policymakers, in their need to cut spending, to avoid singling out specific programs -- such as the National Science Foundation's Directorate for Social, Behavioral, and Economic Sciences -- and to refrain from bypassing independent peer review. The letter, routed to key lawmakers who are preparing to debate the Commerce, Justice and Science appropriations bill for fiscal year 2012, opposes any attempts to eliminate or substantially reduce funding for particular research programs. Defunding specific grants or entire scientific disciplines "sets a dangerous precedent that, in the end, will inhibit scientific progress and our international competitiveness," the group warned. "Everyone understands that legislators face tremendous challenges related to the deficit and the national economy," said Joanne Carney, director of the Office of Government Relations at the American Association for the Advancement of Science (AAAS). "But recently, selected research areas have been unfairly trivialized based on misinformation intended to challenge the scientific review process." Clear-cutting of support for key fields of research "could have a chilling effect on scientists and young people considering a future in science," the group said in its letter dated July 11.

Unfamiliar or seemingly exotic research topics have long been subjected to ridicule, AAAS has previously noted. From 1975 to 1989, for example, the late Sen. William Proxmire (D-Wisconsin) mocked research projects with titles such as "The Sexual Behavior of the Screw-Worm Fly" -- a parasitic insect whose larvae, or maggots, attack livestock and even people, with devastating results. More recently, Sens. Tom Coburn (R-Oklahoma) and John McCain (R-Arizona) have mislabeled as frivolous important projects related to understanding addiction, global climate change, biodiversity and antibiotic mechanisms. Interdisciplinary research -- integrating the physical and biological sciences with insights from social and behavioral fields -- has become increasingly essential to scientific progress and innovation, Carney pointed out. The National Science Foundation is unique among federal agencies in that its research portfolio supports all science and engineering disciplines. The computer revolution, for example, and the transformation of analog data into digital records have spanned the biological and social sciences and could lead to better brain imaging techniques. Similarly, major national investments in U.S. technology will require insights to how people interact with machines. The multi-billion dollar Geographical Information Systems (GIS) industry, which resulted from National Science Foundation (NSF) research, now routinely supports effective disaster-response efforts in the wake of events such as the September 11, 2011 attacks in New York City.

Social, behavioral, and economic research also sheds light on U.S. demographic trends, criminal behaviors, decision-making processes essential to military and national security operations, prosperity indicators such as Gross Domestic Product, and much more. "Simply put, we need all scientists and scientific disciplines working -- alone and together -- to advance our knowledge base," the group concluded. "Allocating federal investments competitively through scientific merit review is the very process that has led this country to be a world leader in science."... Fiscal year 2011 funding for NSF's Directorate for Social, Behavior, and Economic Sciences (SBE) has been estimated at $255 million, the same amount invested in 2010. For 2012, NSF has requested $301 million for its SBE directorate, which is 3.9% of its total budget proposal.

The U.S. Food and Drug Administration has named former Dartmouth Medical School Dean Stephen Spielberg to the newly created position of deputy commissioner for medical products and tobacco, according to an internal letter sent to FDA employees that was obtained by Reuters. The move is part FDA's goal of overhauling its management structure to better regulate an increasingly complex medical industry. The agency has also initiated a search to fill the newly created chief operating officer position. FDA Commissioner Margaret Hamburg promoted Deborah Autor, currently a director of the agency's compliance office, to the job of deputy commissioner for global regulatory operations and policy, according to the letter. "The new organizational alignments more accurately reflect the agency's responsibilities, subject matter expertise and mandates in an ever more complex world, where products and services do not fit into a single category," Hamburg wrote in the letter.

Earlier this year, former Deputy Commissioner Joshua Sharfstein, who was appointed by President Barack Obama in 2009, left the agency to run the state of Maryland's health department. Under Hamburg and Sharfstein, the agency had become more aggressive in its oversight of companies for product-safety problems, shoddy manufacturing and misleading advertisements. Spielberg, who most recently has served as director of personalized medicine at Children's Mercy Hospital in Kansas City, has previously worked with Johnson & Johnson and Merck & Co...

Two new studies released early Wednesday show that AIDS drugs can prevent heterosexuals from acquiring HIV, adding to a growing number of new methods to slow the spread of the virus world-wide. Many researchers now believe that science has developed sufficient tools to contain the pandemic. But tight budgets may limit their deployment. The results are the latest to demonstrate that existing medications are an important tool for prevention as well as treatment of HIV/AIDS, and show their effectiveness in the population hardest hit by HIV globally--heterosexuals in Africa. The findings also are likely to help alleviate concerns that emerged in April after another study was unable to determine whether the drugs protected high-risk women.

Both of the new studies, conducted in different African countries, found that giving antiretroviral drugs to heterosexuals reduced the risk of HIV infection by at least 62%--"which is huge," said Jared Baeten, co-chair of a study led by researchers at the University of Washington International Clinical Research Center. That study examined 4,758 heterosexual couples in Kenya and Uganda in which one partner had HIV but the other didn't. Researchers found that those who received a daily dose of a drug called tenofovir had an average of 62% fewer infections than those taking a placebo, while those who received a drug combining tenofovir and another medication, emtricitabine, had an average of 73% fewer infections. The drugs are marketed by Gilead Sciences Inc. under the brand names Viread and Truvada, respectively. The study, funded by the Bill & Melinda Gates Foundation, wasn't supposed to end until late 2012. But after reviewing ongoing results, an independent Data and Safety Monitoring Board decided Sunday to halt the trial early because the findings were so strong, Dr. Baeten said. "We're stopping a year and a half early--really, on a dime--because the results were so powerful," Dr. Baeten said. Trial participants who were receiving placebo will stop getting it on Thursday, and they will be offered the chance to take either of the antiretroviral medicines, Dr. Baeten said.

A separate study led by the Centers for Disease Control and Prevention of 1,200 uninfected heterosexual men and women in Botswana found that those taking a once-daily dose of Truvada reduced their risk of acquiring HIV by about 63% compared to those taking a placebo. CDC researchers believe the results may be even stronger among participants who adhered closely to the regimen. "This is exciting news for HIV prevention both within the U.S. and globally," said Kevin Fenton, director of the CDC's National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention. "We're beginning to understand that these antiretroviral drugs are powerful tools for prevention toolkits." The CDC had planned to release the results of its four-year study, which it finished earlier this year, at an international AIDS conference in Rome next week. But it accelerated its release to coincide with the other study results, Dr. Fenton said.

The two new studies add to a rapidly expanding suite of prevention methods beyond behavioral efforts such as condoms and abstinence. "As we get more scientific data, the ability to contain the epidemic by multiple weapons gets better and better," said Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases. Over the past year, studies have shown reductions in contracting HIV among uninfected gay men taking AIDS drugs and among women who applied a vaginal gel containing an AIDS drug. Also, infected people treated with the drugs were shown to be 96% less likely to transmit HIV than patients not yet on therapy. And a few years ago, circumcision was proven to slash the chance that a man would acquire HIV. Even before the latest two studies, Dr. Fauci wrote a widely discussed editorial in the journal Science stating, "For the first time in the history of HIV/AIDS, controlling and ending the pandemic are feasible." A major problem is financing for HIV/AIDS, which fell for the first time in 2010 for low- and middle-income countries, according to the Kaiser Family Foundation. But, Dr. Fauci wrote, "Major investments in implementation now will save even greater expenditures in the future."

The next step is to figure out how best to use AIDS drugs for prevention. No one is suggesting that masses of women in Africa or anywhere else be placed on drugs to prevent infection; that would be too expensive, and the drugs can cause side effects. But it might be cost-effective to target high-risk women, such as sex workers, several researchers and advocates said. "The challenge is moving from the trial to real world implementation," Dr. Fenton said. "We need to understand in which populations to apply them" and how to combine them with other prevention tools, such as counseling and HIV testing, he said. The CDC plans to develop guidance for their use in the U.S., he said. The two studies resolve a contradiction that had puzzled researchers. Last year, a study showed that giving AIDS drugs to uninfected gay men reduced their chances of getting infected. But then in April, a study in which women were given the same regimen had to be stopped because it was unable to determine if the drugs had any protective effect, an inconclusive result that was widely considered a setback. The two studies reported Wednesday suggest the inconclusive study had unrecognized problems, perhaps in adhering to the regimen.

In the first agreement between a pharmaceutical company and the new international Medicines Patent Pool, Gilead Sciences announced Tuesday that it would license four of its AIDS and hepatitis B drugs to the pool. The move is particularly important because it includes tenofovir and emtricitabine, which have emerged as important components of AIDS therapy and new prophylaxis regimens, like vaginal microbicides for women and once-a-day pills protecting gay men. Many poor countries now have only older drugs, some of which have harsh side effects. Health advocates have long championed the idea of a pool: an independent agency that would hold patents on drugs and sub-license them to low-cost manufacturers for low or no royalties on the condition that they supply only poor countries. (In Uganda cost cutting has set back anti-AIDS programs.) The pool was created last year, but drugmakers resisted it, wanting to control quality and protect rights to future profits from middle-income countries. Until this week, the only participant was the National Institutes of Health, which turned over a partial patent on an obscure AIDS drug. "This is a great achievement," said James P. Love, a campaigner for lower drug prices who first proposed a pool in 2002. "The other drug companies didn't want Gilead to sign anything, and this will put pressure on them." The pool must negotiate which countries can get which drugs, and Mr. Love said he will watch that carefully. Gilead may benefit, he noted, because it may now get modest royalties from sales in countries where it never bothered to take out patents.

Retroviruses such as HIV are notorious for their ability to dodge the mammalian immune system, but researchers have pinpointed a mechanism by which retrovirus-resistant mice detect and respond to retroviral infection. The body's innate immune system detects pathogens using specific receptors, which then trigger the antibody and cellular responses. Tatyana Golovkina at the University of Chicago, Illinois, and her team infected retrovirus-resistant mice with mouse retroviruses. Virus that had been irradiated with ultraviolet light -- and had thus been rendered incapable of replicating -- was just as able to elicit an antibody response as nonirradiated virus, suggesting that viral entry is enough to trigger the response.

Some more alarming news is coming from the world of antibiotic-resistant superbugs. This time it's a strain of a sexually transmitted disease, gonorrhea, that scientists say has mutated to become resistant to all currently available antibiotics. The bad news was delivered by Magnus Unemo, Makoto Ohnishi and colleagues at the 19th conference of the International Society for Sexually Transmitted Disease Research in Quebec City. It's part of a trend toward antibiotic resistance that has health officials around the world, including the World Health Organization, warning about an impending drug-resistance crisis if new antibiotics are not developed soon. "This is both an alarming and a predictable discovery," Unemo, of the Swedish Reference Laboratory for Pathogenic Neisseria, said in a news release. "Since antibiotics became the standard treatment for gonorrhea in the 1940s, this bacterium has shown a remarkable capacity to develop resistance mechanisms to all drugs introduced to control it." Unemo added that it's too early to tell if the new strain will become widespread, but judging from history, "it may spread rapidly unless new drugs and effective treatment programs are developed." The Booster Shots blog in the LA Times lists a kind of parade of antibiotics used against gonorrhea since the 1940s. First came sulfonamides, followed by penicillin, then on to cephalosporins (oral cefixime and injectable ceftriaxone). Each successive time, gonorrhea became resistant to the previous antibiotic. After cephalosporins, there is nothing new on the horizon. Gonorrhea is one of the most common sexually transmitted diseases in the world. In the U.S. alone, according to the Center for Disease Control and Prevention (CDC), the number of cases is estimated at 700,000 annually. It is asymptomatic in about 50% of infected women and approximately 2-5% of men.

A policy specialist and a healthcare economist both say that the oft-quoted cost of $1.32 billion to bring a new drug to market does not hold up to close scrutiny, reports Genetic Engineering & Biotechnology News (GEN). The researchers emphasize that available cost data cannot be trusted because the numbers are subject to numerous internal and external sources of variability, according to the July issue of GEN. "With heated discussions still taking place over healthcare reform and a regulatory environment increasingly focused on safety, the GEN point of view piece should serve as an important article for multiple discussions on new drug R&D and commercialization costs," says John Sterling, Editor in Chief of GEN. "We hope that the article leads to an informative debate on this crucial issue of new drug research and development costs."

Donald W. Light, Ph.D., a professor at the University of Medicine and Dentistry of New Jersey and the Lokey visiting professor in human biology at Stanford University, and Rebecca Warburton, Ph.D., an associate professor at the University of Victoria (British Columbia), claim that pharmaceutical firms list their R&D costs as high as possible to garner greater prices for their products. Yet, continue the article's authors, a number of independent review groups report that 85% of new drugs exhibit few if any advantages over existing drugs. Noting that the "R" in R&D is basically unknown and highly variable, Drs. Light and Warburton estimate that the median development ("D") cost for a new drug in 2000 was about $60 million (ranging from $13 million to $203 million depending on the type of drug) while the median D cost in 2006 was approximately $98 million (ranging from $21 million to $333 million).

First discovered in 1995, protease inhibitor drugs have dramatically reduced the number of AIDS deaths. Taken in combination with two other anti-HIV drugs, protease inhibitors work by halting the action of the protease enzyme, a protein produced by HIV that is necessary for replication of the virus. However, almost half of HIV patients who initially respond to treatment with protease inhibitors develop drug-resistance strains and stop responding to treatment within eight to 10 months. Currently there are nine FDA approved protease inhibitors, and 21 most common drug-resistant mutations. The main reason for the short-term effectiveness of the drug has to do with the evolution of the drug within the body, said the study's author, Yi Mao, a postdoctoral fellow at the National Institute for Mathematical and Biological Synthesis. In the new study, published today in the journal BMC Structural Biology, Mao used a mathematical modeling technique called elastic network modeling to examine the physical properties and interactions of the proteins. The model reveals where mutations are occurring during the evolution of the HIV-virus proteins and how these mutations help the virus survive. "With this kind of knowledge, better strategies for designing anti-HIV drugs could be developed," Mao said...

Abstract
Background: HIV testing is still stigmatized among many high-risk groups in China while routine syphilis testing has been widely accepted at STI clinics. This project used the platform of a rapid syphilis screening test to expand HIV test uptake. The objective of this study was to use multilevel modeling to analyze determinants of syphilis and HIV testing uptake at STI clinics in China.

Methods: 2061 STI patients at six clinics in Guangdong Province were offered free rapid syphilis and free rapid HIV testing. Test uptake was defined by patient receipt of results and a multilevel model was used to analyze predictors of uptake.

Results: This was the first syphilis or HIV test for the large majority (1388, 77.7%) of participants. Syphilis test uptake and HIV test uptake were high (1681, 81.6%, syphilis test uptake; 1673, 81.2% HIV test uptake). HIV test uptake was significantly concordant with syphilis test uptake (τb = 0.89, p < 0.001). The most parsimonious model of HIV test uptake included the following variables: being married, having a previous HIV test, being unaccompanied, and participating in the last two months of the study.

Conclusions: STI-clinic based screening for syphilis and HIV represents an excellent opportunity for scaling up integrated services, especially in South China where syphilis and sexually transmitted HIV cases are both rapidly increasing. Effective integration of HIV testing into routine clinical practice requires an understanding not only of individual test uptake but also of the broader social context of HIV testing.

Abstract
Background: Pre-exposure prophylaxis (PrEP) is a novel intervention strategy for the prevention HIV transmission. Because several clinical trials are at various stages of completion, it is important to understand the impact of PrEP treatment on the development of the immune response to HIV, particularly in individuals who exhibit breakthrough infections despite PrEP.

Methods: A model of HIV infection, using rhesus macaques and the simian/human immunodeficiency virus (SHIV), was used to evaluate the effects of PrEP on the evolution of the humoral immune response. Time to seroconversion, neutralizing and binding antibody levels, and antibody avidity were measured in 12 rhesus macaques infected during daily or intermittent PrEP with FTC (emtricitabine) or Truvada (FTC/tenofovir combination) and compared with 11 untreated, simian HIV-infected controls.

Results: Macaques that became infected while receiving PrEP exhibited significantly lower peak virus loads during acute infection as compared with untreated animals. Although the timing of seroconversion and SHIV binding and neutralizing antibody levels were not impacted by treatment, lower maturation rates of antibody avidity for anti-p27, gp120, gp160, and gp41 were observed.

Conclusions: This study suggests that reduced virus loads associated with PrEP treatment have little impact on timing of seroconversion and neutralizing/binding antibody levels; however, maturation of antibody avidity was suppressed.

Abstract
Background: Former prison inmates are at risk for HIV and hepatitis C (HCV) infection. This study was designed to understand how former inmates perceived their risk for HIV and HCV infection after release from prison, the behaviors and environmental factors that put patients at risk for new infection, and the barriers to accessing health care.

Methods: This was a qualitative study using individual, face-to-face, semistructured interviews exploring participants' perceptions and behaviors putting them at risk for HIV and HCV infection and barriers to engaging in regular medical care after release. Interview transcripts were coded and analyzed using a team-based general inductive approach.

Results: Participants were racially and ethnically diverse and consisted of 20 men and 9 women with an age range of 22-57 years who were interviewed within the first 2 months after their release from prison to the Denver, Colorado community. Four major themes emerged: (1) risk factors including unprotected sex, transactional sex, and drug use were prevalent in the postrelease period; (2) engagement in risky behavior occurred disproportionately in the first few days after release; (3) former inmates had educational needs about HIV and HCV infection; and (4) former inmates faced major challenges in accessing health care and medications.

Conclusions: Risk factors for HIV and HCV infection were prevalent among former inmates immediately after release. Prevention efforts should focus on education, promotion of safe sex and needle practices, substance abuse treatment, and drug-free transitional housing. Improved coordination between correctional staff, parole officers, and community health care providers may improve continuity of care.

Abstract
Background: In the Kilimanjaro region the mother-in-law has traditionally had an important role in matters related to reproduction and childcare. The aim of this study was to explore the role of the mothers-in-law in prevention of mother-to-child transmission (PMTCT) service utilization and adherence to infant feeding guidelines.

Methods: The study was conducted during 2007-2008 in rural and urban areas of Moshi district in the Kilimanjaro region of Tanzania. Mixed methods were used and included focus group discussions with mothers-in-law, mothers and fathers; in-depth interviews with mothers-in-law, mothers, fathers and HIV-infected mothers, and a survey of 446 mothers bringing their four-week-old infants for immunisation at five reproductive and child health clinics.

Results: The study demonstrated that the mother-in-law saw herself as responsible for family health issues in general and child care in particular. However she received limited trust, and couples, in particular couples living in urban areas, tended to exclude her from decisions related to childbearing and infant feeding. Mothers-in-law expected their daughters-in-law to breastfeed in a customary manner and were generally negative towards the infant feeding methods recommended for HIV-infected mothers; exclusive replacement feeding and exclusive breastfeeding.

Conclusions: Decreasing influence of the mother-in-law and increasing prominence of the conjugal couples in issues related to reproduction and child care, reinforce the importance of continued efforts to include male partners in the PMTCT programme. The potential for involving mothers-in-law in the infant feeding component, where she still has influence in some areas, should be further explored.

Abstract
Background: Targeted interventions (TIs) have been a major strategy for HIV prevention in India. We evaluated the impact of TIs on HIV prevalence in high HIV prevalence southern states (Tamil Nadu, Karnataka, Andhra Pradesh and Maharashtra).

Methods: A quasi-experimental approach was used to retrospectively compare changes in HIV prevalence according to the intensity of targeted intervention implementation. Condom gap (number of condoms required minus condoms supplied by TIs) was used as an indicator of TI intensity. Annual average number of commercial sex acts per female sex worker (FSW) reported in Behavioral Surveillance Survey was multiplied by the estimated number of FSWs in each district to calculate annual requirement of condoms in the district. Data of condoms supplied by TIs from 1995 to 2008 was obtained from program records. Districts in each state were ranked into quartiles based on the TI intensity. Primary data of HIV Sentinel Surveillance was analyzed to calculate HIV prevalence reductions in each successive year taking 2001 as reference year according to the quartiles of TI intensity districts using generalized linear model with logit link and binomial distribution after adjusting for age, education, and place of residence (urban or rural).

Results: In the high HIV prevalence southern states, the number of TI projects for FSWs increased from 5 to 310 between 1995 and 2008. In high TI intensity quartile districts (n=30), 186 condoms per FSW/year were distributed through TIs as compared to 45 condoms/FSW/year in the low TI intensity districts (n=29). Behavioral surveillance indicated significant rise in condom use from 2001 to 2009. Among FSWs consistent condom use with last paying clients increased from 58.6% to 83.7% (p<0.001), and among men of reproductive age, the condom use during sex with non-regular partner increased from 51.7% to 68.6% (p <0.001). A significant decline in HIV and syphilis prevalence has occurred in high prevalence southern states among FSWs and young antenatal women. Among young (15-24 years) antenatal clinic attendees significant decline was observed in HIV prevalence from 2001 to 2008 (OR=0.42, 95% CI 0.28-0.62) in high TI intensity districts whereas in low TI intensity districts the change was not significant (OR=1.01, 95% CI 0.67-1.5).

Conclusions: Targeted interventions are associated with HIV prevalence decline.

These tenofovir concentrations are proxy markers of drug exposure at the actual time of HIV exposure, and some residual systematic differences between the three groups of women could account for some of the variations in HIV risk, despite adjustment for potential confounders. Notwithstanding, our data suggest that cervicovaginal fluid concentrations of tenofovir greater than 1000 ng/mL were required to prevent HIV infection. This value is more than ten times the concentration seen with oral tenofovir disoproxil fumarate and emtricitabine.

What are the implications for HIV prevention research? Detailed analyses of the FEM-PrEP1 data will undoubtedly enhance our understanding of how antiretrovirals prevent HIV infection in women. In the interim, our suggestions for continuing and proposed PrEP research are: first, the effectiveness trials that are underway (registered with ClinicalTrials.gov, numbers NCT00705679,NCT00557245, NCT00448669, NCT00119106) for tenofovir disoproxil fumarate alone and in combination with emtricitabine are crucially needed to corroborate or refute the FEM-PrEP1 trial results and to provide information about HIV effectiveness in diverse populations, various formulations, and in different routes of transmission. Researchers need to factor the FEM-PrEP trial outcome into the information provided to participants. Furthermore the data-review plans, especially the rules for futility, might need to be revisited.

Second, investigators need to revise existing or develop new animal-challenge and tissue models for PrEP to be able to assess varying drug dosages. Specifically, further animal models with which to assess vaginal challenge after oral dosing are needed. Additionally, the models might need an infectious virus inoculum that is closer to physiological values. Third, until there is improved clarity about the threshold concentration of tenofovir that is likely to protect against HIV, the goal in future clinical trials of this drug should be to attain the highest tolerable drug concentrations in the vagina. Options such as combinations of oral and topical formulations could be worth investigation, especially in settings in which anal sex is common in women. Fourth, efforts to enhance adherence in PrEP trials are crucial. Finally, new PrEP formulations, such as intravaginal rings and injectables, will need to be carefully assessed to work out whether the drug concentrations achieved at the site of viral exposure are likely to be high enough to prevent HIV infection.

The FEM-PrEP trial is a sharp reminder of the uncertainty of the scientific endeavor. Success needs an iterative approach to identify the most appropriate drugs, drug concentrations, adherence support, formulations, and dosing regimen for each route of HIV transmission. The proof of principle that antiretroviral drugs can prevent sexual transmission of HIV has reinvigorated HIV prevention. It has created new hope that antiretroviral-based PrEP strategies, especially those that are women-initiated, could in combination with other prevention interventions, finally stem the tide of the HIV pandemic.

We have entered a new era in HIV prevention whereby priorities have expanded from biomedical discovery to include implementation, effectiveness, and the effect of combination prevention at the population level. However, gaps in knowledge and implementation challenges remain. In this Review we analyse trends in the rapidly changing landscape of HIV prevention, and chart a new path for HIV prevention research that focuses on the implementation of effective and efficient combination prevention strategies to turn the tide on the HIV pandemic.