23 SEPTEMBER 2011, VOLUME 12, ISSUE 38

The AIDS Vaccine 2011 conference ended [last] Thursday in Bangkok, Thailand. While a vaccine to help end the pandemic remains elusive, scientific advances are being made. About 850 scientists, researchers and others met for four days to discuss progress on finding a vaccine to prevent HIV infection. It's the only conference to focus exclusively on that. Mitchell Warren, head of the AIDS Vaccine Advocacy Coalition, or AVAC, gives the meeting fairly high marks... "We are in a terrific moment in the field and I must say it is terrifically exciting to be able to do this meeting here in Bangkok. It's not just good science, but to be in the country where the largest AIDS vaccine trial in the world took place -- and the first trial to demonstrate that a vaccine was possible -- it's pretty exciting timing," he said. That vaccine candidate is known as RV-144. The results of the trial involving about 16,000 participants were announced in 2009. They showed a protection rate of about 31 percent - not nearly good enough to go to market, but good enough to show it can be done.

Warren said, "Over the last two years, an unprecedented international collaboration has been underway to try to understand why we got the modest effect in that trial that we did." What they found were not definite answers, but rather new signals of what direction to take next. "It is what we call hypothesis generating and there is going to need to be some additional studies to confirm that. But these are the first signals we've ever had," he said. A follow-up trial to RV-144 will be held in 2014. It will reflect new the data and direction developed since 2009. Meanwhile, there is a vaccine trial that's currently recruiting 2,200 participants in about 20 U.S. cities. It's sponsored by the HIV Vaccine Trials Network. HVTN 505 is the world's largest ongoing HIV vaccine study and uses a combination of two experimental vaccines. It will focus on preventing infection among men who have sex with men and transgender women... He added that in these difficult economic times, a comprehensive strategic plan is needed for HIV/AIDS. The near and midterm strategies, he says, should include scaling up treatment and care, condoms, male circumcision, microbicides and the use of antiretroviral drugs as a preventive measure. The long term strategy is an AIDS vaccine. "The near term and midterm strategies are the ones that are going to help us begin to control the epidemic. The long term strategy will get us an end to the epidemic," he said.

Mozambican Health Minister Alexandre Manguele announced on Wednesday that clinical trials of a vaccine against HIV, the virus that causes AIDS, will begin this month and last for about a year and a half. A combination of vaccines, known as ADN-MVA, will be used, ADN is a primary stimulus intended to unleash an immune response, while MVA is used to strengthen the immune response caused by ADN. Manguele said that the ADN-MVA combination has already been tested scientifically in Tanzania and Sweden, with encouraging results. "The study that will now be held in Mozambique is known as a 'Phase I/II clinical trial' and seeks to assess the safety and immunogenicity of the primary intradermal vaccination with ADN and the intramuscular strengthening with MNA", said the Minister. The trial subjects will be "young and healthy volunteers in Mozambique". In layman's terms, the trial is intended to see whether the vaccine has any harmful effects, and whether it produces any immune response against HIV. "It is an initial phase of research to contribute to the development of a preventive vaccine", said Manguele. "Only in subsequent studies with these vaccines can the degree of protection against HIV be verified"... The trials will be carried out by the National Health Institute (INS) and by Maputo Central Hospital (HCM). Dr Ilesh Jani, Director of the INS, told the press conference that Mozambique has the capacity, in terms of human resources and equipment, to perform the trial. He stressed the importance of undertaking studies in Mozambique, because there are various types of the HIV virus in different parts of the world - with the attendant risk that a vaccine developed for particular countries might not work in others. Jani said there is no risk to the health of the 24 young volunteers. They are all HIV-negative, with a very low probability of contracting HIV.

During a debate last week for Republican presidential candidates and in interviews after it, Representative Michele Bachmann called the vaccine to prevent cervical cancer "dangerous." Medical experts fired back quickly. Her statements were false, they said, emphasizing that the vaccine is safe and can save lives. Mrs. Bachmann was soon on the defensive, acknowledging that she was not a doctor or a scientist. But the harm to public health may have already been done. When politicians or celebrities raise alarms about vaccines, even false alarms, vaccination rates drop. "These things always set you back about three years, which is exactly what we can't afford," said Dr. Rodney E. Willoughby, a professor of pediatrics at the Medical College of Wisconsin and a member of the committee on infectious diseases of the American Academy of Pediatrics... Use of the vaccine was disturbingly low even before the Bachmann flap, health officials say. That is partly because of the recent climate of fear about vaccines in general, and partly because some parents feel that giving the vaccine somehow implies that they are accepting or even condoning the idea that their young daughters will soon start having sex...

Historically, Dr. Willoughby said, vaccine scares have caused vaccination rates to drop for three or four years, and have led to outbreaks of diseases that had previously been under control, like measles and whooping cough. Measles cases in the United States reached a 15-year high last spring, with more than 100 cases, most in people who had never been vaccinated. Once the disease begins to reappear, parents become worried and start vaccinating again. With cervical cancer, Dr. Willoughby said, "unfortunately, the outbreak is silent and will take 20 years to manifest." This time, he said, there will be no symptoms to scare parents back into vaccinating their daughters until it is too late. HPV infection is extremely common -- the most common sexually transmitted infection in the United States. More than a quarter of girls and women ages 14 to 49 have been infected, with the highest rate, 44 percent, in those ages 20 to 24. Millions of new infections occur each year, and researchers think that at least half of all adults have been infected at some point in their lives. The genital region is teeming with HPV, and any kind of intimate contact -- not just intercourse -- can transmit the virus. In most people, HPV is harmless: The immune system fights it off. But in some people, for unknown reasons, the viruses persist and can cause cancer. Although the HPV vaccine was initially approved in 2006 to prevent cervical cancer, more recent data has shown that HPV also causes cancers of the penis, anus, vagina, vulva and parts of the throat. Many scientists think that the vaccine can prevent those diseases as well.

President Obama is not giving up when it comes to trying to introduce competition to expensive drugs made by biotechnology. Tucked into the president's deficit reduction plan released on Monday was a proposal to reduce the market exclusivity offered to brand-name biologic drugs to seven years, down from the 12 incorporated in the 2010 federal health care legislation. That would allow so-called generic versions of such drugs to reach the market sooner, saving an estimated $3.5 billion in federal health spending over 10 years, or a little over one-tenth of 1 percent of the $3 trillion the president's deficit reduction plan is supposed to save in a decade. Biologic drugs are proteins made in living cells, like Avastin and Herceptin for cancer and Enbrel and Humira for rheumatoid arthritis. Such drugs can cost tens of thousands of dollars a year and are not subject to the same rapid onset of generic competition as drugs made in chemical factories, like Lipitor and Prozac.

The issue was a thorny one during the debate in Congress over the health care legislation. The biotechnology industry argued it needed 12 years of freedom from lower priced competition to recoup research and development costs. Any less, it argued, would retard innovation. The generic industry, as well as many insurers and employers who pay health care bills, said a much shorter period would suffice. Mr. Obama urged seven years as a "generous compromise." But Congress, with bipartisan support, went with 12 years. Now the president hopes for another chance. The proposal released Monday "is consistent with where the administration has been since Day 1," a senior administration official said at a press briefing. Will the deficit situation cause Congress to reconsider? The biotechnology industry is likely to lobby very hard against that. The Food and Drug Administration has yet to define the procedures for getting such generic biologic drugs, often called "biosimilars," approved. But various generic drug companies and some big pharmaceutical companies are getting ready. Gardiner Harris reported in an article on Monday that generic drug companies in China and India are also gearing up.

As the White House helps boost the efforts of NIH chief Francis Collins to create an ambitious new center for translational biomedical research, the agency has struck a deal with the FDA and the bleeding-edge crowd at DARPA to fund a new R&D program for the center which will create a computer chip that can better probe potential drug toxicity. The agencies will provide $140 million over five years to back the project for the center, which has stirred some opposition in Congress. The new project will grow three-dimensional groups of cells combined by type, say kidney or lung cells, which will be able to illustrate the toxic effects of an experimental treatment, according to Science magazine. Collins tells the magazine that the program is "really ambitious." And DARPA, the military's R&D group, is already out scouting for proposals. Collins' proposed National Center for Advancing Translational Sciences will be responsible for the project, provided it survives an effort in Congress to scuttle funding. Some lawmakers have urged Collins to hold off on his efforts to recruit a chief for the center, a major initiative he put together to accelerate early-stage research. But as Science notes, the agency nevertheless pushed ahead with an ad for the job. Questions about NCATS have also raised uncertainties about the National Center for Research Resources, an NIH division that is supposed to be wrapped up in the new operation.

The quest for low-cost HIV treatment may lie in finding virus-fighting properties among the thousands of drugs already approved by the Food and Drug Administration, according to Vojo Deretic, chair of molecular genetics and microbiology department at the University of New Mexico. Deretic's team has received a $1 million grant from the Bill & Melinda Gates Foundation to study existing drugs that could increase a cell's ability to combat HIV. The researchers are focused on a cellular process called autophagy, or Greek for "self-eating," in which cells produce specialized cellular subunits, called autophagosomes, that remove unwanted material. Thousands of drugs will be examined in search of compounds that encourage cells to produce autophagosomes in large numbers, said Deretic. Central to the task is a screening device that produces high-resolution photographs of the cell interiors. A state-of-the-art computer program will "look inside the cell and see structures and quantify them," Deretic explained. Rogaine, a hair regrowth treatment, is among the medicines showing early promise, said Deretic. Others include albuterol, a fast-acting asthma drug, and lithium, which is used to treat depression and bipolar disorder. Later in the two-year study, the team will test combinations of the most promising drugs. "My feeling is it's going to take two [drugs] in a combination," said Deretic. "We want to find the cheap drug, relative to what a new drug would cost, and see if it can do the trick," Deretic said.

A study published in the New England Journal of Medicine last month has demonstrated that antiretroviral treatment can prevent the spread of HIV, in addition to saving those infected from sickness and death. Armed with this new data, President Obama should lead the world in a massive effort to expand access to treatment and rid humanity of AIDS -- the most devastating disease of our time. But just as the end of AIDS has finally come within reach, we are witnessing an unprecedented drop in financial and political support for the cause. The Joint United Nations Programme on HIV/AIDS and the Kaiser Family Foundation reported in August that donor funding for HIV/AIDS leveled in 2009 and then declined -- 10 percent -- in 2010 for the first time ever. The United States, which accounts for more than half of global contributions to fight the disease, disbursed $700 million less in 2010 than in 2009. And projected U.S. funding in 2011 is roughly $28 million less than in 2010.

This is a great shame, as millions of people receiving treatment worldwide depend on these funds to stay alive. Our support should be increasing. AIDS remains the leading cause of orphanhood and of death among women of reproductive age. It is a major driver of opportunistic infections -- particularly tuberculosis -- and keeps tens of millions of Africans mired in poverty. Barack Obama has achieved great things thus far in his presidency. He has helped reform the U.S. health-care system to ensure that all citizens have access to the medical attention they may need. He has implemented the Global Health Initiative to streamline U.S. development aid programs. Last year he announced a $4 billion commitment to the Global Fund to Fight AIDS, Tuberculosis and Malaria, the premier multilateral funding instrument dedicated to controlling these diseases. He is in a position to make a game-changing impact on the war against AIDS. The Lancet medical journal recently modeled new investments in that fight and a strategic shift to proven prevention methods. It was demonstrated that doing so could yield dramatic progress and reduce overall costs within just a few years. The new HIV-prevention study supports this plan. Early treatment reduces the chance of passing HIV to an uninfected sexual partner by 96 percent -- conferring near-total protection. A single treatment course could prevent multiple infections, reducing the need for additional treatments and saving countless public health dollars.

U.S. government researchers plan to design a chip that can check whether new drugs are toxic before they are tested in people, potentially speeding up the development of new therapies. The chip would lump together human cells from the liver, heart, muscles and other organs, then diffuse a drug through them. Multiple readouts would then show how different proteins, genes and other compounds in the cells react to the medicine. "If things are going to fail, you want them to fail early," Dr. Francis Collins, the director of the National Institutes of Health (NIH), told Reuters on Friday. "Now you'll be able to find out much quicker if something isn't going to work." Collins said a drug's toxicity is one of the most common reasons why promising compounds fail. But animal tests -- the usual method of checking a drug before trying it on humans -- can be misleading. He said about half of drugs that work in animals may turn out to be toxic for people. And some drugs may in fact work in people even if they fail in animals, meaning potentially important medicines could be rejected. The project aims to bring together new knowledge from engineering, biology and toxicology. The cells in the chip will be grouped next to each other so they can interact, much as they would in a human body. The chip will be tested with drugs that are known to be safe, and those that are toxic, to look at how the readouts compare. The Defense Advanced Research Projects Agency (DARPA) and the NIH will each spend up to $70 million over five years on their own separate programs to develop the chip. They will also work with the Food and Drug Administration, the U.S. drugs regulator, which could potentially use the chip to test drugs during the approval process. It takes an average of 15 years and more than $1 billion to get approval to sell a drug in the United States, according to the drug industry group PhRMA. "We know the development pipeline has bottlenecks in it, and everyone would benefit from fixing them," Collins said.

Gilead Sciences Inc. announced on Monday that its investigational once-daily "Quad" tablet reduced HIV viral loads in treatment-naive trial participants as well as a regimen combining existing treatments. The Foster City, Calif.-based company plans to request Food and Drug Administration "priority review" by the end of this year, rather than the first quarter of next year as previously announced. Approval could be granted as early as mid-2012. The Quad pill combines two experimental agents, the integrase inhibitor elvitegravir and the boosting agent cobicistat, with Truvada (emtricitabine/tenofovir). In this latest Phase III trial, Quad was compared with ritonavir-boosted atazanavir (Reyataz) plus Truvada. At the end of 48 weeks, 90 percent of patients taking Quad achieved an HIV RNA viral load of less than 50 copies/mL, compared with 87 percent of participants on the control regimen. While 5.1 percent dropped out of the control group due to adverse events (primarily due to elevated bilirubin levels), just 3.1 percent of Quad participants did so. "The 90 percent response rate observed on the Quad arm in this study is an unprecedented result and speaks to the potency, safety, and convenience of an integrase-based single-tablet regimen," said Norbert Bischofberger, PhD, Gilead's chief scientific officer. "Overall the data are good ... mostly in line with investor expectations," said Cowen and Co. analyst Philip Nadeau. "I think there might have been a little bit of expectation for statistical superiority, but only from a few outliers."

A compound that protects sharks from viruses could be used to create a broad-spectrum antiviral agent for human use, U.S. researchers say. The compound, squalamine, has been safely tested in human trials for the treatment of cancer and several eye disorders, leading researchers to believe it could quickly produce news drugs to treat viral infections ranging from dengue and yellow fevers to hepatitis, a release by the Georgetown University Medical Center said Monday. Georgetown researcher Michael Zasloff said the compound has shown antiviral activity against these human pathogens, some of which cannot presently be treated effectively. "To realize that squalamine potentially has broad antiviral properties is immensely exciting, especially since we already know so much from ongoing studies about its behavior in people," Zasloff, a professor of surgery and pediatrics at Georgetown, said. Scientists have long wondered how sharks, which possess very primitive immune systems, can so effectively resist viruses. "We may be able to harness the shark's novel immune system to turn all of these antiviral compounds into agents that protect humans against a wide variety of viruses," Zasloff said. "While many antibacterial agents exist, doctors have few antiviral drugs to help their patients, and few of those are broadly active."

Gamers have solved the structure of a retrovirus enzyme whose configuration had stumped scientists for more than a decade. The gamers achieved their discovery by playing Foldit, an online game that allows players to collaborate and compete in predicting the structure of protein molecules. After scientists repeatedly failed to piece together the structure of a protein-cutting enzyme from an AIDS-like virus, they called in the Foldit players. The scientists challenged the gamers to produce an accurate model of the enzyme. They did it in only three weeks. This class of enzymes, called retroviral proteases, has a critical role in how the AIDS virus matures and proliferates. Intensive research is under way to try to find anti-AIDS drugs that can block these enzymes, but efforts were hampered by not knowing exactly what the retroviral protease molecule looks like. We wanted to see if human intuition could succeed where automated methods had failed," said Dr. Firas Khatib of the University of Washington Department of Biochemistry. Khatib is a researcher in the protein structure lab of Dr. David Baker, professor of biochemistry. Remarkably, the gamers generated models good enough for the researchers to refine and, within a few days, determine the enzyme's structure. Equally amazing, surfaces on the molecule stood out as likely targets for drugs to de-active the enzyme. "These features provide exciting opportunities for the design of retroviral drugs, including AIDS drugs," wrote the authors of a paper appearing Sept. 18 in Nature Structural & Molecular Biology. The scientists and gamers are listed as co-authors.

This is the first instance that the researchers are aware of in which gamers solved a longstanding scientific problem. Fold-it was created by computer scientists at the University of Washington Center for Game Science in collaboration with the Baker lab. "The focus of the UW Center for Game Sciences," said director Dr. Zoran Popovic, associate professor of computer science and engineering, "is to solve hard problems in science and education that currently cannot be solved by either people or computers alone." The solution of the virus enzyme structure, the researchers said, "indicates the power of online computer games to channel human intuition and three-dimensional pattern matching skills to solve challenging scientific problems." With names like Foldit Contenders Group and Foldit Void Crushers Group, the gamer teams were fired up for the task of real-world molecule modeling problems. The online protein folding game captivates thousands of avid players worldwide and engages the general public in scientific discovery.

Health providers and advocates are divided over a bill intended to bring Massachusetts into compliance with CDC recommendations on making HIV testing a routine part of medical care. The bill would enable the informed consent process for HIV testing to be conducted orally and documented by the provider in medical records. Currently, the state requires written patient consent specifically for the HIV test. However, to accommodate privacy concerns, legislators this year added a provision that would require a health care provider to obtain a patient's written consent every time his or her HIV-related information is shared with outside providers. Some stakeholders support that requirement. Others, however, balk at the bill they once backed, saying it would hinder HIV patients' ability to receive care in a timely fashion.

A coalition of more than 100 health care providers - including Fenway Health, the Massachusetts Medical Society, and the Massachusetts Hospital Association - is urging legislators and health officials in Gov. Deval Patrick's administration to block the bill. The measure has passed two subcommittees and awaits a full Senate vote. "The entire country is going in the other direction, to make information sharing easier and more thorough," said Dr. Howard Heller, president of the Massachusetts Infectious Diseases Society. "This is a step backward." The bill's supporters say such safeguards remain necessary to protect patients' privacy. "HIV is still stigmatized, and many people fear the disclosure of HIV status," said Ben Klein, AIDS law project director at Gay & Lesbian Advocates & Defenders. Other backers of the measure include the American Civil Liberties Union of Massachusetts and the nonprofit AIDS Action Committee of Massachusetts. Rebecca Haag, president and CEO of AIDS Action, noted her support of the bill's provision requiring health care providers to document that they offered HIV testing to a patient.

The crowd of health issues jostling for a share of Kenya's inadequate health budget is expanding, with activists calling for an increase in resources for the management of non-communicable diseases (NCDs), which account for more than 50 percent of hospital deaths and admissions. "We need to see more commitment in terms of resources; we have policies and guidelines for the management of non-communicable illnesses, but we need strategic focus on operational implementation," said Andrew Suleh, medical superintendent of Mbagathi District Hospital in the Kenyan capital, Nairobi... The UN World Health Organization's 2011 World Health Statistics report, states that the Kenyan government spends just 5.8 percent of its budget on health; this represents less than half of the 15 percent pledged by African leaders under the Abuja Declaration of 2001. Worryingly for health activists, government spending on health appears to be shrinking rather than growing; in 2000, health spending was 9 percent of total government expenditure and reliance on external sources for health funding rose from 8.8 percent in 2000 to 26.8 percent, according to WHO. "The health service is overwhelmed; at Kenyatta [National Hospital, the country's largest referral facility] we perform open-heart surgery twice a week - our waiting list is up to 2013," said James Munene, head of the Cardiac Unit. "We are dealing with a situation where the population has grown but we still have the same number of facilities and the same number of qualified personnel. "Risk reduction efforts are not working - the messages about HIV prevention and TB and other communicable illnesses have been very clear and evident, but we don't see efforts to ensure proper nutrition, exercise - the things that could prevent many of these NCDs," he added. "Perhaps because we have so much starvation in parts of the country we are afraid to advise those who have food on how to eat right."

Against a backdrop of two consecutive rejections by the Global Fund to fight AIDS, Tuberculosis and Malaria and flat-lined funding from the US President's Emergency Plan for AIDS Relief, HIV activists worry that any move to increase funding for NCDs could mean less for HIV... Kamau noted that if all Kenyans who required HIV treatment had access to it, the government would reduce the costs of treating opportunistic infections, freeing up vital manpower and other resources to treat other illnesses. But boosting resources for NCDs would be beneficial to people with HIV, as studies show they are at higher risk for conditions such as cardiovascular disease. According to a 2011 study of more than 12,000 HIV-positive men and women in western Kenya, there is a high prevalence of hypertension and obesity - both linked to cardiovascular disease - among HIV-positive patients in that part of the country... The authors recommended that HIV care in sub-Saharan Africa should include identification and management of cardiovascular risk factors. "Programmes in sub-Saharan Africa that focus solely on HIV care are missing a major opportunity to improve population health status at a substantial future cost," they said. A 2010 study of a programme by the NGO, Family Health International, to integrate cardiovascular disease management and HIV care in Kenya found that cardiovascular disease screening and management were feasible in routine HIV care. According to Mbagathi Hospital's Suleh, the demands for more health funding should not put the various health activists at odds with each other, but rather should unite them to ensure the government fulfils its obligations. "This should not be a competition - the same government is responsible for ensuring that HIV and NCDs are fully funded," said Suleh. "There has been more emphasis on communicable diseases like HIV, malaria and TB; there must be a balance and proper planning to ensure all these vital areas receive due attention."

Bionor Pharma ASA (BIONOR), the Norwegian developer of an experimental AIDS treatment, said the injection lowered viral levels in patients' blood and helped some of them stay off daily pills for more than a year. As many as 30 percent of patients in a study of Bionor's Vacc-4x were able to stay off antiretroviral therapy more than a year after they stopped, compared with 18 percent who got a placebo, the Oslo-based company said in a statement today. The results were presented at a conference in Bangkok. The findings may help Bionor revive Vacc-4x after saying in October it would scrap the shot because six-month data showed it didn't work, sending the stock down 81 percent. A month later the company reversed the decision after further analysis showed the treatment lowered viral levels. It now plans three more trials to see if it can improve on today's results, including one combining Vacc-4x with Celgene Corp. (CELG)'s cancer drug Revlimid. "We don't see this as a standalone alternative to antiretroviral therapy," Vidar Wendel-Hansen, Bionor's chief medical officer, said in an interview. "What we do see is the long-term potential to train the immune system to take over the role of antiretroviral therapy. That's the goal."...

Unlike the pills that are the mainstay of HIV treatment, Vacc-4x is a so-called therapeutic vaccine designed to fight the virus by marshaling the body's immune system against it. While the shot hasn't yet been shown to subdue the virus as well as antiretroviral therapy, regular injections that keep it at relatively low levels may save patients from the side effects and costs associated with pills. The trial involved 135 patients who had been using anti- AIDS drugs to control HIV for at least six months. Two-thirds received six shots of Vacc-4x while taking their regular pills over 28 weeks, then stopped taking the drugs. The other third received an injection of water. Six months later, those who got the shot had an average 70 percent reduction in the amount of virus in their blood compared with the level before they started pill therapy. More than a year after they went off treatment, 30 percent of them remained pill-free, compared with 18 percent of the placebo group. "Several years ago I would have been tremendously excited" by the results, Michael Saag, director of the Center for AIDS Research at the University of Alabama at Birmingham, said in an e-mail. "Now I find it interesting, but not as compelling," Saag said. "The reason is that we have growing evidence that, even with no detectable virus among folks not on antiretroviral therapy, there is evidence of increased inflammation." Even low levels of viral replication -- which the pills control -- could be harmful to patients in the long-term, according to Saag.

Having to contend with U.S. army drones and the crossfire between the Taliban and the Pakistani army, the residents of Pakistan's tribal areas find access to treatment for HIV/AIDS harder than in most other parts of the world. Currently, people living with HIV/AIDS (PLWHA) in the Federally Administered Tribal Areas (FATA) must cross the porous border into Afghanistan and take a circuitous route to Peshawar, capital of the Khyber Pakhtunkhwa province, to get timely anti-retroviral treatment (ART)... Pakistan's northwest became a sanctuary for Taliban and Al-Qaeda elements that poured over the border following the U.S.-led invasion of Afghanistan in 2001... The Pakistan government, with financial and technical support from the World Health Organisation (WHO), had established a family care centre for providing free ART treatment to PLWHA in 2005. So far, the centre has registered 531 patients, with 277 from FATA and 254 from Khyber Pakhtunkhwa. At the ART centre, Dr. Shahid Ali says patients from FATA find it extremely hard to travel to Peshawar and there are fears that many will die for lack of treatment...

The WHO's Dr. Omar Ali says the government has been requested to facilitate access to FATA to provide treatment to the patients there, but there has been no response. Ali says the number of PLWHA was increasing because of intravenous drug use, lack of screening facilities in the blood banks, use of unsterilised equipment by dentists and recycling of disposable syringes. When the ART centre started functioning patients were unwilling to visit it because of the social stigma associated with HIV/AIDS, but such attitudes are gradually changing... WHO's Ali said the centre has had to depend on drugs imported from India which are provided free of cost to people who turn up for treatment. The Peshawar centre, which is staffed by doctors and nurses trained in India, provides ART, management of opportunistic infections, voluntary counselling and testing services and also acute care of HIV-related infections... Jamila Bibi, a staff nurse at the ART centre, said many women and children with HIV are facing a critical situation because they are denied access to treatment. "Quite a few contact us over telephone, but we cannot do anything for them unless the patients come to the centre." Most FATA patients are poor and illiterate and do not get the priority in care and treatment they deserve, she said. Last month, a girl Naseema died because of stoppage of ART, Bibi added.

In a sign of progress against one of the great plagues of the last generation, a dwindling number of New York City AIDS cases has been diagnosed over the last eight years, according to new statistics released [last] Friday. The number of adults with newly diagnosed AIDS dropped to 2,225 in the 2011 fiscal year, which ended on June 30. That total was 25 percent lower than the total for the year before (2,969 new diagnoses), and 47 percent lower than in the 2003 fiscal year, when there were 4,164 new cases, according to the Mayor's Management Report, which was released on Friday. Dr. Monica Sweeney, assistant commissioner of the Bureau of H.I.V. Prevention and Control of the city's Department of Health and Mental Hygiene, said the decline was a "proxy for improved care." "It's not that people are not infected" with H.I.V., the virus that causes AIDS, she said. "It is that they are taking medications, they're able to be more adherent, treatment has become easier." But she added that the number of newly diagnosed cases with H.I.V. has also been going down, though those numbers were not included in the report.

New infections were most common among men under 30, especially black and Latino men, who have sex with men; black women; and to a lesser extent Latina women, she said. On the other hand, Dr. Sweeney said, because of programs directed at pregnant women and drug users, it is rare for babies to be born infected, and "people getting infected from intravenous drug use has gone from the thousands to 185" in 2009, the last year of complete data available. The historic numbers tell a striking tale of an epidemic that crested and then began to fall as the means of transmission became better understood and drug treatment was simplified from a handful of pills to a single capsule containing three medications. City charts show 52 new diagnoses of AIDS before 1981, rising to 160 in 1981, 540 in 1982, 1,097 in 1983 and then soaring to a peak of 12,745 in 1993 before beginning a gradual decline to the present levels.

When the sole Community Care Centre in Jammu and Kashmir providing medical and psychosocial services to people living with HIV/AIDS (PLWHA) closed down for lack of patients it was a sure sign that the north Indian state had beaten back dire forecasts... The latest sentinel survey conducted by the JKAPCS in 2010 shows an HIV prevalence of 0.03 percent - down from the 1.2 percent in the survey conducted in 2009. According to official statistics, of the 4,846 test samples taken in the year 2008 only three persons were found to be HIV positive, and of the 4,840 samples tested in 2009 not one was found positive. Such figures contrast sharply with grim projections made by the National AIDS Control Organisation (NACO) in 2002-2003 that some 40,000 people would be infected with HIV within two years in Jammu and Kashmir and that 20,000 people would die of AIDS by 2015. Since 1997, only 193 new patients have tested positive for HIV, most of them urban males in the 15-45 age group. There are now 2,787 PLWHA, including 800 women and 176 children, in this state with a population of 12.5 million people. NACO figures released in June say there are 683 people on anti-retroviral therapy (ART) in Jammu and Kashmir where the total number of people recorded as ever getting full-blown AIDS stands at 1,123 - out of which 203 have died.

The low and declining rates have not made life easier for PLHWA, because of the strong social stigma attached to the disease and difficulties in accessing anti-retroviral drugs... Experts say that the majority of HIV sufferers in the state are youth and troops deployed in strength in the state to fight armed separatist insurgency... Latief said that the major route for transmission of the virus in the state is sexual. "Cases involving spread of HIV through blood transfusion have hardly come to our notice," Latief told IPS. He added that the valley faces threat of HIV mainly from troops, truck drivers, migrant labourers and people who travel regularly. Wani told IPS that the slow economic development of the state may be one reason for low HIV prevalence. "It has been noted that well-developed cities and towns fall prey more easily to HIV. Since Kashmir is largely underdeveloped, we are on the safer side," Wani says. Other factors that may have contributed to the low HIV prevalence is the intensive awareness campaigns and counselling mounted by the JKAPCS... Besides providing counselling to thousands of schoolteachers, the JKAPCS has trained 840 imams (mosque leaders) and about 500 granthis or Sikh temple preachers...

Kenya aims at achieving 80 percent of HIV testing among its approximately 40 million people by 2013, an HIV expert said here [last] Friday. Peter Cherutich, the Deputy Director and Head of HIV Prevention at the National Aids and STIs Control Program (NASCOP) said that the country is keen on ensuring that majority of its population know their HIV status to effectively fight the disease. "As a country, we want everyone, be it children, old men or pregnant women to know their HIV status," Cherutich told an HIV forum in Nairobi. He added that Kenya will also strengthen measures to take care of HIV patient so that once a person knows their status, they can thereafter access anti-retroviral drugs to reduce chances of transmission. Currently, according to Cherutich, about 60 percent of Kenyans know their HIV status. "Various strategies have been put in place to encourage all adults to know their HIV status but about 40 percent of people in this country have never undergone a HIV test," he noted.

An early stage trial of Sangamo BioSciences Inc's HIV treatment found that the gene therapy reduced levels of the virus and even eliminated it in one patient with a naturally occurring gene mutation. The very small Phase 1 trial tested the SB-728-T gene therapy, which is designed to disrupt the CCR5 gene used by HIV to infect cells of the immune system. If shown to be safe and effective, the treatment could end the need for the antiretroviral drugs now used to keep the virus that causes AIDS in check by suppressing viral replication in the blood. Trial results presented in Chicago on Sunday at the Interscience Conference on Antimicrobial Agents and Chemotherapy show a "statistically significant relationship between estimated modification of both copies of the CCR5 gene and viral load," said Dr. Carl June, trial investigator and director of translational research at the University of Pennsylvania's cancer research institute. In a statement, June said the results suggest the need to increase the frequency of the modified cells in HIV-infected patients, which could lead to a "functional cure" for AIDS, but the means of achieving this have not been clarified.

Sangamo said earlier this year that a single infusion of the treatment improved immune system damage in nearly all of the subjects analyzed in the first trial of the therapy in humans. The 10 patients in the trial were on antiretroviral therapy when the study began. After four weeks, six of them went on a "treatment interruption," during which they stopped taking antiviral medication for 12 weeks. Viral load decreased in three of the six subjects, with one patient's viral load reduced to undetectable levels. That patient carried a naturally occurring mutation in one copy of his CCR5 gene. Humans contain two copies of each gene, one from the father and one from the mother, which sometimes are referred to as the alleles of a gene. "Since one copy of his gene was already disrupted naturally, twice as many of his cells were 'biallelically' modified," Sangamo Chief Executive Officer Edward Lanphier said in a telephone interview, meaning that both members of the CCR5 gene pair were knocked out. He estimated that between 5 percent and 10 percent of HIV patients carry the genetic mutation... Lanphier said Sangamo will move ahead with a strategy to maximize the number of cells that can be "biallelically" modified by SB-728-T. Options include targeting only the small segment of patients with mutated CCR5 genes or using "strategies that boost the amount of engraftment of modified cells."

New global guidelines on best practices to counter non-communicable diseases (NCDs) could avert up to 15 percent of preventable deaths over the next 20 years, but may fail to gain currency in countries already struggling to keep pace with communicable diseases, maternal and child mortality and other public health issues, economic and health experts say. "Many countries are saying this issue of NCDs is an additional burden where we need to put money, and we are not in a position where we can mobilize additional resources," Olivier Raynaud, senior director of health and healthcare industries at the Switzerland-based World Economic Forum (WEF), told IRIN. "This report is saying, 'Careful. If you do not mobilize resources today, can you afford the cost tomorrow of not doing the right thing?'" The WEF and Harvard School of Public Health released two reports on 18 September analyzing the economic impact - especially in low and middle-income countries - of an unchecked, increasing prevalence of NCDs, and the action countries must take to prevent them. Their launch marked the beginning of a UN two-day conference on NCDs, coinciding with the opening of the General Assembly autumn session...

But Dan Chisholm, a health economist at the World Health Organization (WHO), concedes that the package -- which does not include any sort of specific global funding goals or national budget strategies -- could be a hard sell, as "the real size of the magnitude of this problem has taken a while to be realized". "There are always competing priorities, so if you have a low-income country in Africa with a raging HIV epidemic or high rates of child or maternal morality, it's a very tough choice of how to invest your scarce dollars," explained Chisholm, who helped present the reports. "I suppose this is really just trying to raise awareness of the consequences of NCDs and that they need to be built into a sort of development agenda."... "What we need to confront this crisis is the sort of thing we have done with malaria, tuberculosis and HIV," said Jonathan Brown, vice-president of the International Diabetes Federation. "We need to use those models to set up non-physicians, local people, to monitor the situation. "There are lots of ways to approach this and it doesn't have to be expensive, it doesn't have to be cumbersome. We just have to get going on this thing." The conference on NCDs is set to adopt an "action-oriented outcome document", acknowledging the economic and social risks of NCDs and calling for "multisectoral national policies and plans for the prevention and control" of NCDs by 2013. It also brings to light the issue of mental and neurological disorders, presented as periphery NCDs that still cause significant financial loss and are often linked with the four core broad diseases. "You could have visited a country before the UN summit and said, 'What's your plan for NCDs?' and they would have said, "'What NCDs?'," said Raynaud. "This meeting will enable that discussion and lead different nations to make a plan. It's a start."

Last year, an estimated two million women around the world developed breast cancer or cancer of the cervix (the neck of the womb); more than 600,000 died - the equivalent of six large passenger planes crashing every single day. These are the results published by a team from the University of Washington in Seattle in the British journal, The Lancet, ahead of the non-communicable diseases conference at the UN in New York. The study is the first global analysis of trends in cervical and breast cancer incidence and mortality, using data from 187 countries. It shows that while breast cancer deaths are concentrated among older women in richer countries, 76 percent of cases of cervical cancer now occur in developing countries, where the incidence of the disease is still increasing. Almost half those cases are in women under 50. The authors conclude: "Our findings show that in developing countries in the reproductive age groups, breast and cervical cancer are substantial problems of a similar importance to major global priorities such as maternal mortality." ... While figures are abundantly available from Western Europe and North America, as well as India, whole swathes of Africa, especially central Africa, provide hardly any data at all. And even in those African countries that do attempt to keep records, accuracy is still patchy. Asked how much confidence he had in the statistics, Raphael Lozano, professor of global health at Seattle's Institute for Health Metrics and Evaluation, told IRIN: "We were fortunately able to gather information from countries with cancer registries, such as Malawi, Uganda, Namibia, Zimbabwe and South Africa. Both Cape Verde and South Africa had vital registration data [births and deaths]. And we relied on verbal autopsy information from nationally representative studies in Mozambique and Burkina Faso. Our models allowed us to borrow strength from data from countries within the same region and others... A vaccination against HPV is now available and - together with regular screening - is one of the factors reducing the incidence and mortality from cervical cancer in richer countries. But with the vaccine initially costing about US$300 for a course of three doses it was priced beyond the reach of developing countries. Now the Global Alliance for Vaccines and Immunisation, GAVI, has negotiated a price of $5 a dose with the manufacturers, and is planning to roll out the vaccine in eligible countries soon.

Researchers have found a way to prevent HIV from damaging the immune system, in a new lab-based study published in the journal Blood. The research, led by scientists at Imperial College London and Johns Hopkins University, could have important implications for the development of HIV vaccines... The research shows that HIV is unable to damage the immune system if cholesterol is removed from the virus's membrane. Usually, when a person becomes infected, the body's innate immune response provides an immediate defence. However, some researchers believe that HIV causes the innate immune system to overreact and that this weakens the immune system's next line of defence, known as the adaptive immune response. In the new study, the researchers removed cholesterol from the membrane surrounding the virus and found that this stopped HIV from triggering the innate immune response. This led to a stronger adaptive response, orchestrated by immune cells called T cells. These results support the idea that HIV overstimulates the innate response and that this weakens the immune system. Dr Adriano Boasso, first author of the study, from Imperial College London, said: "HIV is very sneaky. It evades the host's defences by triggering overblown responses that damage the immune system. It's like revving your car in first gear for too long. Eventually the engine blows out. "This may be one reason why developing a vaccine has proven so difficult. Most vaccines prime the adaptive response to recognise the invader, but it's hard for this to work if the virus triggers other mechanisms that weaken the adaptive response." HIV takes its membrane from the cell that it infects. This membrane contains cholesterol, which helps to keep it fluid. The fluidity of the membrane enables the virus to interact with particular types of cell. Cholesterol in the cell membrane is not connected to cholesterol in the blood, which is a risk factor for heart disease but is not linked to HIV. Normally, a subset of immune cells called plasmacytoid dendritic cells (pDCs) recognise HIV quickly and react by producing signalling molecules called interferons. These signals activate various processes which are initially helpful, but which damage the immune system if switched on for too long. In collaboration with researchers at Johns Hopkins University, the University of Milan and Innsbruck University, Dr Boasso's group at Imperial have discovered that if cholesterol is removed from HIV's envelope, it can no longer activate pDCs. As a consequence, T cells, which orchestrate the adaptive response, can fight the virus more effectively. The researchers removed cholesterol using varying concentrations of beta-cyclodextrin (bCD), a derivative of starch that binds cholesterol. Using high levels of bCD they produced a virus with a large hole in its envelope. This permeabilised virus was not infectious and could not activate pDCs, but was still recognised by T cells. Dr Boasso and his colleagues are now looking to investigate whether this inactivated virus could be developed into a vaccine.

Journal Reference:
Boasso A, Royle CM, Doumazos S, Aquino VN, et al. Over-activation of plasmacytoid dendritic cell inhibits anti-viral T-cell responses: a model for HIV immunopathogenesis. Blood, 2011

Abstract
Background: In a randomized clinical trial of early versus standard antiretroviral therapy (ART) in HIV-infected adults with a CD4 cell count between 200 and 350 cells/mm3 in Haiti, early ART decreased mortality by 75%. We assessed the cost-effectiveness of early versus standard ART in this trial.

Methods and Findings: Trial data included use of ART and other medications, laboratory tests, outpatient visits, radiographic studies, procedures, and hospital services. Medication, laboratory, radiograph, labor, and overhead costs were from the study clinic, and hospital and procedure costs were from local providers. We evaluated cost per year of life saved (YLS), including patient and caregiver costs, with a median of 21 months and maximum of 36 months of follow-up, and with costs and life expectancy discounted at 3% per annum. Between 2005 and 2008, 816 participants were enrolled and followed for a median of 21 months. Mean total costs per patient during the trial were US$1,381 for early ART and US$1,033 for standard ART. After excluding research-related laboratory tests without clinical benefit, costs were US$1,158 (early ART) and US$979 (standard ART). Early ART patients had higher mean costs for ART (US$398 versus US$81) but lower costs for non-ART medications, CD4 cell counts, clinically indicated tests, and radiographs (US$275 versus US$384). The cost-effectiveness ratio after a maximum of 3 years for early versus standard ART was US$3,975/YLS (95% CI US$2,129/YLS-US$9,979/YLS) including research-related tests, and US$2,050/YLS excluding research-related tests (95% CI US$722/YLS-US$5,537/YLS).

Conclusions: Initiating ART in HIV-infected adults with a CD4 cell count between 200 and 350 cells/mm3 in Haiti, consistent with World Health Organization advice, was cost-effective (US$/YLS <3 times gross domestic product per capita) after a maximum of 3 years, after excluding research-related laboratory tests.

A new analysis of the only AIDS vaccine trial ever to report positive results suggests that a novel antibody response led to the modest level of efficacy seen in the study. Although numerous questions remain, researchers in this failure-riddled field say the new finding may point the way to a more effective vaccine. The so-called RV144 vaccine trial, which involved 16,000 heterosexuals in Thailand who were at low risk of HIV infection, sparked controversy in September 2009 when researchers reported their results (Science, 2 October 2009, p. 26). People who received the vaccine, a combination of two different preparations, had a 31% lower risk of becominginfected than those given a placebo. This marginal level of protection reached statistical significance in just one of the three types of analyses performed, and critics of the study questioned whether the results had any real meaning. Now the research team, led by the U.S. Military HIV Research Program and the Thailand Ministry of Public Health, have analyzed stored samples from 41 vaccinated people who became infected and 205 who did not and discovered that an antibody response to a little-studied portion of HIV's surface protein correlated with the protection observed in the study. AIDS researchers have long searched for the so-called correlates of immunity so they can determine which immuneresponses a vaccine should aim to trigger. Virologist Jerome Kim of the Walter Reed Army Institute of Research in Rockville, Maryland, who presented the new results from RV144 on 13 September at an international AIDS vaccine conference in Bangkok, stressed that they do not want to overstate the new insights. "We're looking at an association between a biomarker and a correlate of risk," Kim said. "The results of this case-controlled study are purely hypothesis generating and just provide a starting point." AIDS researchers have put much effort into developing vaccines that trigger antibodies that can "neutralize" HIV in test-tube studies, preventing it from entering uninfected cells. But as Kim and other presenters explained, the RV144 analysis did not find any correlation between neutralizing antibodies and protection. Rather, they discovered that protected people had higher levels of a "binding" antibody that attaches to a region of HIV's surface protein called V1/V2.

Breast milk antibody both neutralizes human immunodeficiency virus (HIV) and kills HIV-infected cells, according to a paper in the September 2011 issue of the Journal of Virology. "This finding indicates that enhancement of these responses through vaccination could help reduce HIV transmission via breastfeeding," says corresponding author Sallie Permar of Duke University, Durham, NC. While HIV-specific antibodies have been identified in breast milk, this is the first study to investigate the virus-blocking functions of these antibodies. Nonetheless, the statistics indicate that breast milk antibodies are doing an incomplete job of protecting babies from HIV transmission. Nearly half of the 350,000 new infant HIV infections occurring annually are transmitted via breast milk. Permar's study provides perspective: it shows that the magnitude of anti-HIV responses in breast milk is low compared to those in plasma. Thus, the need to enhance that response.

Fortunately, the study's results suggest that current systemic HIV vaccine candidates may be effective in enhancing anti-HIV functions of breast milk antibody, and reducing postnatal HIV transmission. Permar et al. found that breast milk antibody's activity against HIV and HIV-infected cells is mediated by IgG antibodies that originate in the blood stream, rather than IgA antibodies, which are produced in the mammary gland. The alternative to immunologic intervention, formula feeding, "is not a viable option for reducing this mode of transmission in resource poor areas with high HIV prevalence, as it is associated with high infant mortality from diarrhea and respiratory illnesses," says Permar. "While maternal and/or infant antiretroviral prophylaxis during the period of breastfeeding is effective in reducing infant transmission, HIV transmission continues to occur in the setting of optimal prophylaxis and the effects of this long-term prophylaxis on infant growth and development are not known. Moreover, long-term prophylaxis is a challenge for resource poor areas." But a maternal or infant vaccine would be ideal for eliminating post-natal HIV transmission, she says.

Following the failure of a wide range of attempts to solve the crystal structure of M-PMV retroviral protease by molecular replacement, we challenged players of the protein folding game Foldit to produce accurate models of the protein. Remarkably, Foldit players were able to generate models of sufficient quality for successful molecular replacement and subsequent structure determination. The refined structure provides new insights for the design of antiretroviral drugs.

This past year, a Berlin man, Timothy Brown, became world famous as the first--and thus far only--person to apparently have been cured of his HIV infection. Brown's HIV disappeared after he developed leukemia and doctors gave him repeated blood transfusions from a donor who harbored a mutated version of a receptor the virus uses to enter cells. Now, researchers report promising results from two small gene-therapy studies that mimic this strategy, hinting that the field may be moving closer to a cure that works for the masses. At the Interscience Conference on Antimicrobial Agents and Chemotherapy in Chicago, Illinois, this weekend, researchers reported preliminary results from tests of a novel treatment in 15 HIV-infected people designed to free them from the need to take antiretroviral drugs. The studies, conducted separately on the East and West coasts of the United States, attempt to make the immune system resistant to HIV by crippling a receptor, known as CCR5, on T cells that the virus uses during the infection process. The man who donated blood for Timothy Brown's transfusions had naturally defective CCR5 receptors. The trial participants had T cells removed from their blood and then modified in the laboratory with a designer enzyme engineered by Sangamo BioSciences in Richmond, California. The enzyme, called a zinc finger nuclease, clips the gene for the CCR5 receptor and disables it. Ten billion modified cells were then reinfused into the participants' bodies, and the new data show that about 25% of cells had the mutant CCR5s. The studies found that modified T cells persisted for more than 6 months in several patients.

In one provocative case reported in Chicago yesterday, a patient who received the gene therapy and then stopped taking antiretroviral drugs had HIV return within a month, as typically happens when people interrupt their treatment. But a few weeks later, the virus began to decline, and it dropped to undetectable levels in concert with evidence that the gene therapy had altered his T cells. "Those kinetics are very different from what I've seen in treatment interruption studies, and we've done many," says Pablo Tebas, an infectious disease clinician at the University of Pennsylvania who heads the East Coast study of six participants. "This patient goes down, way down." Tebas recognizes that his study is uncontrolled and that they've seen this response in only one patient. What's more, the patient already had a natural advantage because he has a crippled CCR5 gene in one of the two copies he inherited. Tebas suspects that the gene therapy coupled with his natural CCR5 mutation combined to lead to the dramatic result. "This is a very small experiment, and I don't think it's a cure by any means, but the Berlin patient is only one patient, and it changed research priorities," Tebas says. "This shows that there's a correlation between antiviral activity and the proportion of modified cells. It shows a path forward." Although researchers do not expect the gene therapy to entirely clear HIV from the body, they hope it will create a "functional cure"--in other words, contain the virus to such a powerful extent that people no longer need antiretrovirals.

This prospective, cross-sectional study of HIV testing at two sexually transmitted infection clinics compares testing results from the ARCHITECT HIV Ag/Ab Combo fourth generation assay against the current standard of care in North Carolina (third generation enzyme immunoassay testing with western blot confirmation and reflex nucleic acid amplification testing of pooled seronegative samples). In this setting, the assay reported a sensitivity of 100%, a specificity of 99.9%, and a median turn-around time of 26.1 h.

Abstract
Objectives: To investigate temporal trends in HIV incidence rates and to assess changes over time in associated risk factors.

Methods: Since 1995, the SurvUDI network has conducted surveillance among IDUs recruited in harm reduction programmes in eastern central Canada. Among the 11,731 participants, 2903 repeaters were initially HIV-negative. HIV incidence was calculated and compared for two time periods (1995-2002 vs. 2003-2009). Multivariate Cox proportional hazard models with time-dependent covariates were used to assess risk factors associated with HIV seroconversion. Interactions between covariates and time periods were examined.

Results: The overall HIV incidence rate was 2.7 per 100 person-years [95% confidence interval (CI) 2.4-3.1]. It significantly decreased from 3.1 per 100 person-years in 1995-2002 to 2.2 person-years in 2003-2009. Sex, needle borrowing, and cocaine as most often injected drug were independent and stable determinants of HIV seroconversion. Age, daily injection, sex work and being recruited in an urban area showed significant interactions with time. Being aged 25 years and older, injecting daily and being recruited in an urban area predicted HIV incidence in 1995-2002 but were no longer risk factors in 2003-2009. HIV incidence increased significantly among younger IDUs and sex work emerged as a new determinant of HIV incidence in 2003-2009.

Conclusions: HIV incidence has decreased over time but remains high among IDUs in eastern central Canada. Associations between risk factors and HIV incidence have changed. Further research is needed to better understand HIV transmission among younger IDUs and IDU sex workers.

Abstract
Background: Physiologic and behavioral changes during pregnancy may alter HIV-1 susceptibility and infectiousness. Prospective studies exploring pregnancy and HIV-1 acquisition risk in women have found inconsistent results. No study has explored the effect of pregnancy on HIV-1 transmission risk from HIV-1-infected women to male partners.

Methods: In a prospective study of African HIV-1-serodiscordant couples, we evaluated the relationship between pregnancy and the risk of HIV-1 acquisition among women and HIV-1 transmission from women to men.

Results: Three thousand three hundred and twenty-one HIV-1-serodiscordant couples were enrolled, 1085 (32.7%) with HIV-1 susceptible female partners and 2236 (67.3%) with susceptible male partners. HIV-1 incidence in women was 7.35 versus 3.01 per 100 person-years during pregnant and nonpregnant periods [hazard ratio 2.34, 95% confidence interval (CI) 1.33-4.09]. This effect was attenuated and not statistically significant after adjusting for sexual behavior and other confounding factors (adjusted hazard ratio 1.71, 95% CI 0.93-3.12). HIV-1 incidence in male partners of infected women was 3.46 versus 1.58 per 100 person-years when their partners were pregnant versus not pregnant (hazard ratio 2.31, 95% CI 1.22-4.39). This effect was not attenuated in adjusted analysis (adjusted hazard ratio 2.47, 95% CI 1.26-4.85).

Conclusions: HIV-1 risk increased two-fold during pregnancy. Elevated risk of HIV-1 acquisition in pregnant women appeared in part to be explained by behavioral and other factors. This is the first study to show that pregnancy increased the risk of female-to-male HIV-1 transmission, which may reflect biological changes of pregnancy that could increase HIV-1 infectiousness.

Abstract
Objective: Development of an effective vaccine or topical compound to prevent HIV transmission remains a major goal for control of the AIDS pandemic. Using a nonhuman primate model of heterosexual HIV-1 transmission, we tested whether a topical microbicide that reduces viral infectivity can potentiate the efficacy of a T-cell-based HIV vaccine.

Design: A DNA prime and rAd5 virus boost vaccination strategy was employed, and a topical microbicide against the HIV nucleocapsid protein was used. To rigorously test the combination hypothesis, the vaccine constructs contained only two transgenes and the topical microbicide inhibitor was used at a suboptimal dose. Vaccinees were exposed in the absence and presence of the topical microbicide to repeated vaginal R5 simian human immunodeficiency virus (SHIV)SF162P3 challenge at an escalating dose to more closely mimic high-risk exposure of women to HIV.

Methods: Infection status was determined by PCR. Antiviral immune responses were evaluated by gp120 ELISA and intracellular cytokine staining.

Results: A significant delay in SHIV acquisition (log-rank test; P=0.0416) was seen only in vaccinated macaques that were repeatedly challenged in the presence of the topical microbicide. Peak acute viremia was lower (Mann-Whitney test; P=0.0387) and viral burden was also reduced (Mann-Whitney test; P=0.0252) in the combination-treated animals.

Conclusions: The combined use of a topical microbicide to lower the initial viral seeding/spread and a T-cell-based vaccine to immunologically contain the early virological events of mucosal transmission holds promise as a preventive approach to control the spread of the AIDS epidemic.

A survey (Mansergh) of 454 HIV-negative gay men in four US cities (New York, Los Angeles, Chicago and San Francisco) has found that men with lower educational attainment (high school only) were more likely to use antiretrovirals informally for HIV prevention, either as pre-exposure prophylaxis (PrEP) or post-exposure prophylaxis (PEP), than men who had had further education. In a parallel survey of 557 HIV-positive gay men, men with lower educational attainment were, similarly, more likely to share their antiretroviral pills with HIV-negative partners to use as PrEP or PEP. Taken together, 22% of the men in the two surveys were under 30, 35% in their 30s and 43% 40 or over. A third were black, 38% white and the rest Hispanic or of other ethnicity. Roughly a third each of the sample had education only to high school level, to some college qualification, or to a university degree.

The survey asked both groups if they had used PrEP or PEP or, in the case of the HIV-positive men, provided it to others, in the last six months. Informal use of PrEP or PEP was still comparatively uncommon; only a few per cent of those surveyed overall had used ARVs as prevention or provided them in the previous six mnoths. However men with high-school-only education were two to six times more likely to report using one of these strategies. In the negative group, 5% of men with only high school education had used PrEP compared with 1% of others, and 8% had used PEP compared with 3% of others. In the positive group, 6% of men with only high school education had provided PrEP compared with 1% of others and 8% had provided PEP compared with 2%. Men in their 30s and black men were also more likely to provide ARVs to partners for use as PrEP or PEP than other groups. In multivariate analysis, lower educational level remained statistically significant in the case of PEP, but not with PrEP. HIV-negative men with high-school-only education were 3.5 times more likely to use PEP than others. HIV-positive men with high school-only education were 2.7 times more likely to provide PEP than men with some college education and 9.3 times more likely to provide it than men with university degrees. This is a survey of informal (non-prescribed) use of ARVs as prevention and, while some of the PrEP/PEP use may reflect difficulties with safer sex, in may also reflect two other things: firstly, gay men and especially black gay men with lower socioeconomic status are more likely to have HIV and may therefore encounter partners with HIV more often or judge themselves to be at higher risk; and secondly gay men with better educations may be better at getting healthcare providers to prescribe PEP or PrEP.

Journal References:
--Mansergh G et al. 'Less education' is associated with use and sharing of antiretroviral medications for prophylaxis of HIV infection by US men who have sex with men. Sexually Transmitted Infections, early online publication, 2011.
--Al-Tayyib A et al. Knowledge of and attitudes towards pre-exposure prophylaxis (PrEP) for HIV prevention among men who have sex with men in Denver, Colorado. Tenth AIDS Impact Conference, Santa Fe, New Mexico, abstract 207, 2011.

A Brief Review of the Estimated Economic Burden of Sexually Transmitted Diseases in the United States: Inflation-Adjusted Updates of Previously Published Cost Studies
HW Chesson, TL Gift, K Owusu-Edusei, G Tao, et al.

Discordance Between Spermatozoa Detection and Self-Reported Semen Exposure
MF Gallo, JD Sobel, AM Rompalo, S Cu-Uvin, et al.

Condom Use Among US Adults at Last Sexual Intercourse, 1996-2008: An Update From National Survey Data
JE Anderson, L Warner, M Macaluso.

Infections Missed by Urethral-Only Screening for Chlamydia or Gonorrhea Detection Among Men Who Have Sex With Men
JL Marcus, KT Bernstein, RP Kohn, S Liska, SS Philip.

Identifying Opportunities for Chlamydia Screening Among American Indian Women
MM Taylor, B Reilley, S Tulloch, M Winscott, et al.

Original Study
Trends in Antimicrobial Resistance in Neisseria gonorrhoeae Isolated in Canada: 2000-2009
I Martin, G Jayaraman, T Wong, G Liu, et al.

Prevalence and Determinants of High-Risk Human Papillomavirus Infection in Middle-Aged Indian Women
C Sauvaget, BM Nene, K Jayant, R Kelkar, et al.

Chlamydia Partner Services for Females in California Family Planning Clinics
YY Yu, JA Frasure-Williams, EF Dunne, G Bolan, et al.

Circumcision Among Men Who Have Sex With Men in London, United Kingdom: An Unlikely Strategy for HIV Prevention
AC Thornton, S Lattimore, V Delpech, HA Weiss, et al.

The Prevalence of Genital HPV and Factors Associated With Oncogenic HPV Among Men Having Sex With Men and Men Having Sex With Women and Men: The HIM Study
AG Nyitray, RJ Carvalho da Silva, ML Baggio, B Lu, et al.

A Randomized, Controlled Trial of inSPOT and Patient-Delivered Partner Therapy for Gonorrhea and Chlamydial Infection Among Men Who Have Sex With Men
RP Kerani, M Fleming, B DeYoung, MR Golden.

The Impact of Anogenital Warts on Health-Related Quality of Life: A 6-Month Prospective Study
M Drolet, M Brisson, E Maunsell, EL Franco, et al.

Chlamydia trachomatis Prevalence and Risk Behaviors in Parturient Women Aged 15 to 24 in Brazil
VM Pinto, CL Szwarcwald, C Baroni, LL Stringari, et al.

Feasibility of Incorporating Self-Collected Rectal Swabs Into a Community Venue-Based Survey to Measure the Prevalence of HPV Infection in Men Who Have Sex With Men
M Gilbert, M Kwag, W Mei, C Rank, et al.

County-Level Sexually Transmitted Disease Detection and Control in Texas: Do Sexually Transmitted Diseases and Family Planning Clinics Matter?
K Owusu-Edusei, SR Doshi.

Evaluation of the Polyclonal ELISA HPV Serology Assay as a Biomarker for Human Papillomavirus Exposure
SE Coseo, C Porras, LE Dodd, A Hildesheim, et al.

Utility of Antimicrobial Susceptibility Testing in Trichomonas vaginalis-Infected Women With Clinical Treatment Failure
EA Bosserman, DJ Helms, DJ Mosure, W Secor, et al.

Editorial
Sustainable Antimicrobial Surveillance Programs Essential for Controlling Neisseria gonorrhoeae Superbug
JR Dillon.

Accepting the Universal Truths of Cervical Human Papillomavirus Epidemiology in Pursuit of the Remaining Mysteries
M Schiffman, JC Gage, MA Clarke.

Testing Men Who Have Sex With Men for Urethral Infection With Chlamydia trachomatis and Neisseria gonorrhoeae Is Only Half the Job, and We Need the Right Tools
J Schachter, SS Philip.

Case Report
Resistant Trichomoniasis: Successful Treatment With Combination Therapy
P Nyirjesy, J Gilbert, LJ Mulcahy.

Grant Amount: Total of $20,000,000 for fiscal year 2012.

The National Institute of General Medical Sciences invites applications for Centers that will support the determination of the structures of macromolecular complexes among and between components of the human immunodeficiency virus (HIV) and the components of host cells. The goal of this Funding Opportunity Announcement (FOA) is the continuation and/or creation of Centers dedicated to the determination of the high-resolution structures of these complexes. In order to succeed, these Centers must collaborate among themselves and must reach out to the biological community doing research aimed at identifying and validating the presence of these complexes, including sharing of data by timely submission of structural information to appropriate databases. Centers are additionally encouraged to move the knowledge envelope beyond the determination of static structures and into an understanding of the dynamics of complexes with an eye toward informing "mechanism-based drug design." While the purpose of this FOA is not to directly fund specific drug development, the establishment of new technologies/methodologies to advance drug design is desirable. Methods and studies that could elucidate the structural basis for anti-viral resistance are also desirable. The goal of this announcement is to attract the best scientists in relevant fields to attack the problem of characterizing HIV-related macromolecular complexes. Hence the application should focus on: the specific problems to be solved, approaches to be used, identification of potential bottlenecks, a plan for outreach and collaboration to the wider HIV biology community, a workable management plan along with milestones, and the commitment and past experience of the investigators.

Sponsor(s):
National Institutes of Health
National Institute of General Medical Sciences

Funder's Fund ID: RFA-GM-12-003

Letter of Intent Date: 12/07/2011
Application Due Date: 01/06/2011
Project Start Date: 07/01/2012
Fund Duration: Up to five years.

Application Process: Applicants are required to prepare applications according to the current PHS 398 application forms in accordance with the PHS 398 Application Guide.

AIDS Research and Human Retroviruses. Abstracts from AIDS Vaccine 2011, Bangkok, Thailand, 12-15 September 2011. Online ahead of print: 15 September 2011.

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David Kato - human rights activist, friend, and colleague - was murdered in his home in Kampala, Uganda on 26 January 2011.

In recognition of his life and courage, and the continued struggle of lesbian, gay, bisexual, transgender and intersex (LGBTI) individuals around the world, partners committed to eliminating violence, stigma and discrimination have established the David Kato Vision & Voice Award.

Inspired by his work, the award recognizes the leadership of individuals who strive to uphold the numerous dimensions of sexual rights for LGBTI people. Sexual rights are an evolving set of entitlements related to sexuality that contribute to the freedom, equality and dignity of all people, and are an important aspect of human rights. The realization of these rights is also an integral element to a meaningful HIV response among these marginalized groups.

The International AIDS Society (IAS), in partnership with the U.S. National Institutes of Health (NIH) and the NIH-supported Centers for AIDS Research (CFAR), has launched a new round of the joint research grant programme, Creative and Novel Ideas in HIV Research (CNIHR). The programme supports projects exploring new approaches to pressing scientific questions such as the long-term survival of individuals with HIV infection, mechanisms behind establishment of viral reservoirs, new approaches for prevention of HIV transmission, and innovative models of health care delivery. It is designed to promote innovative research and new ideas from early-stage investigators whose primary focus has previously been in fields of scientific inquiry other than HIV/AIDS. It aims at recruiting and training tomorrow's leading HIV researchers from across many areas of science, whose work will benefit not only HIV, but other fields of research as well.

The first step of the competitive application process is open on the CNIHR website (www.cnihr.org) and will close on 17 October 2011. Applicants will be asked to complete a two-step process to assess the quality of their research projects. Awardees will be selected by mid-April 2012. Successful applicants will be invited to the XIX International AIDS Conference (AIDS 2012), in Washington D.C. 22-27 July 2012, where they will be officially awarded. They will also have the opportunity to attend an HIV orientation seminar with leading experts and take part in a networking session during the conference.