The Weekly NewsDigest is a compilation of HIV prevention research media coverage and relevant science in peer-reviewed journals; material on
other reproductive health issues; and matters of policy and politics relevant to HIV prevention research, development and advocacy.
Its purpose is to raise awareness around the range of opinions and information about HIV prevention research disseminated in the press and
scientific journals and provide a neutral, objective basis for decision-making and evidence-based advocacy.
One of the most promising, proven methods for preventing H.I.V. in Africa is being implemented much more slowly than international health authorities recommended... Their goal is to circumcise more than 20 million men, 80 percent of 15-to-49-year-olds, in 14 African countries, by 2015. But only about 600,000 men, less than 3 percent, have been circumcised so far, recent data shows. In South Africa, the epidemic's epicenter, with 5.6 million H.I.V.-positive people, about 145,000 circumcisions have been performed; the goal is 4.3 million... American officials say the 80 percent goal would cost about $2 billion, but would save $16.5 billion by preventing four million infections and their lifelong treatment costs. Some countries, notably Kenya and Tanzania, are making great strides, and experts see promising starts in Zimbabwe, Rwanda, South Africa and elsewhere... But various obstacles have slowed mass circumcision campaigns in many countries: a dearth of political or logistical support from governments and traditional leaders; cultural misconceptions; and in some places requirements that doctors, not nurses or physician assistants, perform circumcisions... Kenya is furthest along, with about 330,000 circumcisions, a third of the government's goal, which exceeds the international health agencies' goal... Local health organizations are deeply involved, and nurses and physician assistants, called clinical officers, can perform circumcisions there. Kenya is also using high-volume strategies that do not require hospitals...
South Africa, Zambia, Zimbabwe and other countries confront more daunting problems, experts say, including the expectation that doctors perform circumcisions. In South Africa, women's groups worry that circumcision will encourage men to stop using condoms, putting women at risk for H.I.V. and other sexually transmitted diseases... South Africa may turn the corner. At Orange Farm, site of a major circumcision study, many men are being circumcised, and their infection risk has declined by a remarkable 76 percent. Researchers there pioneered a quasi-assembly-line method, with nurses performing pre- and post-circumcision procedures and doctors sweeping in to quickly perform each operation. Jacob Zuma, South Africa's president, and Goodwill Zwielithini, king of the Zulus, the largest ethnic group, have become circumcision advocates. And the country has committed $33 million to the effort. By contrast, President Yoweri Museveni of Uganda recently said circumcision is not scientifically proven to prevent H.I.V. and that only premarital abstinence and marital monogamy are sure to work. Only 9,000 of the 4.2 million circumcisions needed in Uganda have been performed... In some countries, medical circumcision campaigns have encountered cultural barriers. Rumors have spread that circumcised men are promiscuous. And definitions of circumcision vary among ethnic groups practicing it... African men often want circumcision, not just because of H.I.V. prevention, but because some believe it makes sex better, researchers say... Some experts also hope the circumcision devices, the Shang Ring and PrePex, will win approval and hasten adoption of circumcision. The devices are plastic rings placed on the penis and worn at home for a week... Dr. Caroline Ryan of the State Department's Office of Global AIDS Coordinator, said "any device would be a game changer in circumcision."
While other scientists successfully shrank beakers, tubes and centrifuges into diagnostic laboratories that fit into aluminum boxes that cost $50,000, George Whitesides had smaller dreams. The diagnostic tests designed in Dr. Whitesides's Harvard University chemistry laboratory fit on a postage stamp and cost less than a penny. His secret? Paper. His colleagues miniaturized diagnostic tests so they could move into the field with tiny pumps and thread-thin tubes. Dr. Whitesides opted for a more novel approach, reasoning that a drop of blood or urine could wick its way through a square of filter paper without any help. And if the paper could be etched with tiny channels so that the drop followed a path, and if that path were mined with dried proteins and chemically triggered dyes, the thumbnail-size square could be a mini-laboratory -- one that could be run off by the thousands on a Xerox machine. Diagnostics for All, the private company Dr. Whitesides founded four years ago here in Boston's Brighton neighborhood to commercialize his inspirations, has already created such a test for liver damage. It requires a single drop of blood, takes 15 minutes and can be read by an untrained eye...
The initial target audience is AIDS patients with tuberculosis who must take powerful cocktails of seven or more drugs. Some drugs damage the liver, and deaths from liver failure are 12 times as common among African AIDS patients as among American ones, Dr. Ryan said, because current liver tests are expensive and require tubes of blood. The paper test was developed with a $10 million grant from the Bill and Melinda Gates Foundation... The company's office here is nothing fancy. The space is sublet from a nanotechnology company in an office park where pride of place belongs to an Acura dealership. Half the lab is piled with high-tech junk abandoned by a previous tenant. And for all the elegance of the thinking that went into them, the tests themselves are produced in a remarkably low-tech, low-cost fashion... Multiplying DNA, a key part of tests for viruses, is a bigger obstacle, since that usually requires repeated heating and cooling. "I don't see us doing sequencing," he said. "That's still going to be done in an aluminum box. But we're still a long way from getting to the end of what's inventable." For now, Dr. Whitesides is eager to see his inventions prove their usefulness in the real world...
The medicines that prevent the transmission of H.I.V. from mother to child are highly effective when they are used properly -- that is, taken at the right time in gestation and in the right doses by both mother and newborn. But in resource-poor countries, mothers often give birth at home and rarely visit health clinics. So the problem is getting the medicines to the mothers and babies who need them, and making sure the doses and timing are right. Several years ago, health workers in several African countries hit on an idea: The first time a pregnant woman visits a health clinic, she should be tested for H.I.V. If she is positive, give her the medicines that she and her baby will soon need, as she may never return to the clinic. Clinic workers began packaging the antiretroviral drugs -- pills for H.I.V.-infected mothers and liquids for their babies -- in paper bags with instructions on how to use them. The Mother-Baby Pack was born... If the mother is H.I.V.-positive but has a CD4 count above 350, her Mother-Baby Pack contains the antiretroviral AZT, to be taken beginning at 14 weeks of pregnancy, and nevirapine for the baby, to be given from birth to until he or she is 6 weeks old. For mothers with a CD4 count of 350 or below, the pack includes the same medicine and dosing schedule for the baby, along with a regimen for the mother that involves three, and sometimes four, different antiretroviral drugs. A third pack, for mothers who do not have H.I.V., contains only diet supplements. A pamphlet with instructions in Sesotho, the local language, is included in each pack, and color coding on the packages indicates which drugs to take and when. The pack also includes pictures for those who cannot read. More than 14,000 have been distributed since January... "We are about to evaluate the program and will be able to objectively respond on the impact," said Dr. Mpolai M. Moteetee, the director general of health services in Lesotho. Then, she continued, they will know "how well the pack is received, the mothers' capacity to use the medicines properly, and whether it is aiding in proper treatment." Unicef, which is supplying the boxes for the Lesotho pilot program, is not yet ready to advocate its wide use. Jimmy Kolker, who retired in August as head of H.I.V. programs at Unicef, is watching and waiting. "We don't have the results from this," he said. "But it's a formalized government program, and we have every reason to believe that it will work."
Every time an HIV clinic tells a patient to come back for more testing or for laboratory results there is a risk the patient will never return. This happens so frequently in sub-Saharan Africa, where more than 50 percent of HIV-positive patients drop out of programs before starting treatment, it has it's own terminology: lost to follow-up. With the use of new rapid test kits -- which measure immune system health without having to send samples off site to laboratories and waiting for results -- researchers in Mozambique nearly doubled treatment enrollment and cut the number of patients lost almost in half. Total patient drop out rates before beginning treatment fell from 64 percent to 33 percent, according to results published this week on the Lancet website. The total proportion of patients who initiated antiretroviral therapy treatment increased from 12 percent to 22 percent... "Before the introduction of point-of-care CD4 tests, to obtain a CD4 result involved several steps each with delays," the authors from the Mozambique Instituto Nacional de Saude and the Clinton Health Access Initiative wrote. The process took an average of 10 days. Use of the rapid tests cuts the number of visits a patient will have to make to a clinic, a major barrier when considering care for people who may have to walk long distances to reach a health facility. The rapid tests also cut the time between when a patient enrolls in a treatment program and when he or she starts the medication from 48 days to 20 days. Health workers don't start patients on medication until their CD4 counts fall below a certain level. The rapid tests allowed that level to be identified more quickly, and patients then promptly received medication. Patients who start treatment earlier have a better chance of survival, so the authors emphasized that wider use of rapid testing could help reduce "one of the largest causes of HIV-related mortality": delayed treatment. The study did not follow patients through their first year of treatment, however, and sustaining patient involvement in treatment programs year after year is another challenge for health workers across sub-Saharan Africa.
Off-label use of HIV drugs to treat chronic fatigue syndrome is growing. However, their use comes at a time when some HIV patients can't get access to the medications because of budget cuts, the New York Times reports. Critics point out that antiretroviral drug use for chronic fatigue is based on the idea the condition stems from a retrovirus known as XMRV--a link that's now in serious dispute. In fact, Science magazine published a partial retraction of the XMRV-and-chronic-fatigue study just today. The authors of the original, controversial paper in 2009 have backed away from their XMRV findings, the Wall Street Journal reports. Science also features a new paper investigating the XMRV issue, which reports that labs screening blood for XMRV or XMRV infection in chronic-fatigue patients and healthy donors either didn't find the virus or couldn't reproduce their findings. Some of the authors of the original study still believe in a link between a retrovirus and chronic fatigue, however. "We have to dig in to find the right viruses. We need to keep looking," Judy Mikovits of the Whittemore Peterson Institute told the WSJ. If a retrovirus is the cause of chronic fatigue syndrome, then antiretrovirals used against HIV might be an appropriate treatment. And doctors are perfectly free to prescribe the drugs as they choose, even if that use isn't FDA-approved. But in a budget environment in which AIDS patients are on waiting lists for drugs they can't afford--and states can no longer provide through assistance programs--the idea that some non-HIV patients are using the drugs has touched off the controversy. And, fairly or not, the questions are rebounding on HIV drugmaker Gilead Sciences --partly because the company's pricing has stirred up protests over the years. No one is accusing Gilead of marketing its drugs for off-label use in chronic fatigue patients. And a company spokeswoman said Gilead's own patient assistance programs wouldn't deliberately provide drugs for free for an off-label use.
With Congress focused on finding new ways to slash the federal budget, worries have been growing among the research groups which rely on the NIH that leaner times are in store for the future. The American Association for Cancer Research made its concerns clear when it released a report last week urging Congress to boost its support for the NIH by 8.6%, lifting its 2012 budget to $33.3 billion. This year the budget was cut by $312 million. "It's the first time in as long as many people can remember that the National Institutes of Health and the National Cancer Institute's budgets have declined," AACR lobbyist John Retzlaff told Bloomberg. A Senate panel, though, quickly dashed those hopes by signing off on a $190 million cut to the NIH. And some would be grateful if that's the worst that Congress does. "In the current environment, it could have been worse," Jennifer Zeitzer, director of legislative relations for the Federation of American Societies for Experimental Biology, tells Science. NIH chief Francis Collins has managed to keep lawmakers in back of the National Center for Advancing Translational Sciences, a new division which is supporting more rapid translational work on biomedical research. The Senate bill also specifies that the NIH's National Center for Research Resources is being scrapped for parts.
On Monday, the Department of Health and Human Services announced $1.89 billion in federal funding for HIV/AIDS services. Approximately $813 million of $1.213 billion in Part B funding of the Ryan White Program is designated for state AIDS Drug Assistance Programs, which provide life-saving medicines to low-income HIV patients. A supplement of $8.4 million will help 36 states and territories address specific needs, including projected ADAP shortfalls and core medical care. In addition, $40 million in ADAP Emergency Relief Funding will go toward eliminating or reducing waiting lists, preventing the need for such lists, and/or supporting cost-containment strategies in 30 states. According to the ADAP Advocacy Association, 8,785 patients were on ADAP waiting lists in 10 states as of Sept. 22. A total of $645 million in Part A Ryan White money will go to 52 cities to provide core medical and support services, including $49.6 million for the Minority AIDS Initiative to improve access to care in disproportionately affected communities.
Chlamydia diagnoses last year in Australia grew by 17 percent over the 2009 figure, while gonorrhea diagnoses shot up by 25 percent, the Kirby Institute reported today. More testing does not account for all of the increases, said David Wilson, an associate professor at the University of New South Wales-based institute. "What we are seeing right now is the rate of diagnosis is surpassing the rate of testing, so that indicates there's an increase in overall infection levels," Wilson said. "So there's an epidemic." Wilson said men's lack of condom use is fueling the rise in STDs. Young heterosexuals were the most likely to be infected with chlamydia, with 80 percent of last year's patients ages 15-29. The rate among women almost quadrupled, and it more than tripled among men who have sex with men. MSM last year also had a sharp increase in rectal gonorrhea infections, resulting in the highest population rate of gonorrhea diagnosis across jurisdictions over the last decade. HIV and viral hepatitis remained mostly stable. The 1,043 new HIV diagnoses in 2010 were in line with the 1,000 diagnoses typically seen in each of the last five years, the report noted. Diagnoses of infectious syphilis, largely among MSM, declined to 4.9 cases per 100,000 from 6.7 per 100,000 in 2007. Widespread rapid HIV testing could help Australia meet its UN commitment of halving new HIV infections by 2015, said Rob Lake, executive director of the Australian Federation of AIDS Organizations. It is time to "move beyond this plateau and decrease infection rates," Lake said. "Overseas experience has shown that when rapid HIV testing is offered, testing rates increase, and many people who have never previously tested present for testing."
The rates of chlamydia and gonorrhea diagnoses among the Aboriginal and Torres Strait Islander population last year were substantially higher than among Australia's non-indigenous population, according to a Kirby Institute surveillance report released today. The chlamydia infection rate for Aborigines was more than three times that of other Australians, the institute said. Among Aborigines and Torres Strait Islanders living outside Australian Capital Territory and New South Wales, the gonorrhea rate, 804 diagnoses per 100,000 people in 2010, was almost 27 times higher than the rate of 30 per 100,000 for the non-indigenous population. The rate of infectious syphilis was five times higher among Aborigines than among other Australians. Aborigines, who account for 2.3 percent of Australia's population, suffer numerous health disparities linked to poverty. The population is also far younger than the average age in Australia, said James Ward, an Aborigine who heads the institute's indigenous health program. STD rates were worst among Aborigines ages 16-19 and in remote Outback communities. Many Aborigines also lack STD awareness, he said, as health workers might focus on other concerns seen as more urgent. The HIV diagnosis rate among Aborigines, 4.2 per 100,000 population in 2006-10, was only slightly higher than the non-indigenous rate of 4.1 per 100,000.
Rogerio Bernardo slung a black satchel over his shoulder and waited by the roadside in the morning mist for a bush taxi. In dusty wingtips, frayed pants and a gray pinstripe suit coat so big it swallowed his slender frame, he looked like any peasant farmer dressed up for a trip to town. In fact, Mr. Bernardo, who has AIDS, is in the vanguard of a promising new effort to reverse one of the most worrisome trends in treating the disease: the growing number of patients across Africa who fail to collect their lifesaving antiretroviral medicines. The simple solution devised by Dr. Tom Decroo, a Belgian physician working here in Tete Province for the aid group Doctors Without Borders, was to organize patients into groups of six. They would then take turns making the monthly trip to pick up refills, cutting the number of times each had to go to town -- to just two a year, from 12. A two-year test of his brainstorm here in Tete, comparing about 300 of these groups with patients who continued going alone, found that almost none of those in the groups stopped taking their medicines and only 2 percent died, according to results published in The Journal of Acquired Immune Deficiency Syndromes. By contrast, 20 percent of the other patients quit treatment or died... On a recent morning, it was Mr. Bernardo's turn to go to town. Before he joined the group, if he was short of cash for taxi fare he needed to hike four hours through the bush to the district hospital in Zobue. But as his group huddled against the chill, each member contributed 15 meticais, or about 50 cents, for taxi fare. They also counted out their leftover pills and noted the tally on their medical cards, so a clinician could tell whether they had taken the previous month's pills...
The study of this new approach also found that it profoundly lightened the load on the health professionals who are one of this poor country's scarcest resources, sharply reducing their caseloads at public hospitals and clinics -- and, health economists say, trimming the cost of treatment... Dr. Decroo acknowledged in an interview that the study design for his approach did not produce as high a quality of evidence as a randomized trial would. And Dr. Tim Farley, an AIDS expert with the World Health Organization who was not involved in the research, cautioned in an e-mail that because the program was limited to clinically stable patients, the comparison with other patients might be skewed. But Dr. Farley added, "Reducing the health-system burden from these patients is fantastic and allows the scarce clinical resources to be used for more complicated patients." ...The government of Mozambique has been so encouraged by Dr. Decroo's approach that it has decided to test it in every province this year... The village chief, Aviso Supinho, said that Mr. Alface and Ms. Isaque had raised awareness about AIDS in Nkondedzi and that the groups had improved villagers' lives. "If I'm sick and isolated, kept at home, I'm considered a dead body, though still breathing," Mr. Supinho said. "But when a person is in a group, he feels, 'I'm sick, but I count.'"
University of Utah researchers have discovered a new class of compounds that stick to the sugary coating of the AIDS virus and inhibit it from infecting cells - an early step toward a new treatment to prevent sexual transmission of the virus.
A new study claims that almost 60 per cent of clinical trial protocols for new drugs are amended during the trial, but one-third of those changes could have been avoided. Researchers at the Tufts Centre for the Study of Drug Development found that completed protocols across all clinical trials generally incur 2.3 amendments, with each requiring an average of 6.9 changes to the protocol, leading to significant expense and delay. The analysis, reported in the September-October issue of the Tufts CSDD Impact Report, was heralded as the first to study the impact of protocol changes across the pharmaceutical and biotechnology industries. Study leader, Ken Getz, Tufts CSDD senior research fellow and assistant professor at Tufts University, said he believed the group's findings suggest the root problem is rising protocol design complexity. "Although amendments to protocols of clinical trials are sometimes necessary to optimise study results and ensure patient safety and ethical treatment, study sponsors can minimise the number of protocols through better initial study design and improved recruitment of study volunteers," Getz told Outsourcing-Pharma. "There are numerous causes of protocol amendments: changing development strategies, perceived and real regulatory pressures, difficulties recruiting patients, poor and hasty protocol authoring," he added... Currently, as each new procedure is introduced amendments have to be made to existing protocols, making it an essentially never-ending process, with one-third of all amendments relating to protocol description and patient eligibility criteria, and the median total cycle time to identify and resolve a protocol problem standing at 61 days. "Our study shows that a high percentage of amendments are made before the first patient has even been enrolled," said Getz, "suggesting that more time needs to be spent on the protocol before it is released. But perhaps most startling is the level of profligacy involved in a high percentage of cases where protocol amendments were carried out. "Nearly one third of all changes were deemed 'avoidable'," said Getz, "suggesting an opportunity for industry to save substantial time and billions of dollars through more streamlined, carefully authored and more feasible protocols."
A group of top world economists said Wednesday that adult male circumcision, a top global priority for preventing HIV infection, is not nearly as cost-effective as other methods of prevention. A successful adult male circumcision effort would require "a large public campaign to get people into the clinic," said Bjorn Lomborg, director of the Copenhagen Consensus Center, a Danish think tank focused on cost-effective public spending that commissioned the panel. Getting men to volunteer to be circumcised would not be easy and "it could cause more risky behavior," Lomborg said. The economists conducted a first-ever cost-benefit analysis of the top AIDS-fighting approaches by comparing the costs of prevention and treatment options per lives saved.
The group told representatives of global organizations at Georgetown University that more cost-effective ways to prevent the spread of the disease are an HIV vaccine, infant male circumcision, preventing mother-to-child transmission of the disease and making blood transfusions safe. Each year 2.5 million people are infected with the disease and 2 million die, about 70% of them in Africa, according to the Copenhagen center. Marelize Gorgens, HIV prevention coordinator at the World Bank, disagreed with the economists, saying male circumcision is like a vaccine because it reduces the risk of infection by 60%... The World Bank and the U.S. State Department support a major push for adult circumcision. But the economists estimated the cost-benefit ratio for adult male circumcision at 23:1. They said increasing annual spending on an AIDS vaccine by $100 million would be a better investment -- cost benefit ratio: 12:1 -- because it could potentially eradicate the disease, Lomborg said. Other improvements "are so cheap and effective" they jumped to the top of the list, he said. Preventing mother-to-child transmission by treating HIV-positive pregnant women with medication and improving the blood supply, had a cost benefit of 95:1 and 393:1, respectively. "Making blood transfusions safe costs almost nothing, but we're not doing it," Lomborg said.
Another large study that aims to prevent the spread of HIV by giving uninfected women antiretroviral (ARV) pills has had to redesign the trial because of startling--and negative--interim results. The Microbicide Trials Network (MTN), which is funded by the U.S. National Institutes of Health, today announced that it decided to stop one arm of a study involving more than 5000 women in South Africa, Zimbabwe, and Uganda. The decision followed an interim review of the ongoing trial by an independent monitoring board, which found that the drug tenofovir when used as pre-exposure prophylaxis (PrEP) had less effect in protecting women than anticipated. Although the board did not offer any specifics on how many women became infected on the drug versus placebo, they said continuing with the tenofovir arm was "futile" as it would not yield meaningful results... The study, Vaginal and Oral Interventions to Control the Epidemic (VOICE), began in September 2009 and is not scheduled to end until about 1 year from now. The MTN designed VOICE to compare three different PrEP strategies: tenofovir pills, tenofovir in a vaginal gel, and Truvada pills (a combination of tenofovir and a second antiretroviral, emtricitabine). The tenofovir gel and Truvada pills arms of the study are still under way...
The new results particularly baffled people who follow this promising prevention strategy because there were mixed but encouraging findings in two similar studies reported earlier this year. In April, researchers stopped a study called FEM-PrEP that evaluated Truvada pills in nearly 2000 uninfected young women in South Africa, Kenya, and Tanzania after an interim analysis revealed that continuing was futile. But then in July, an early look at infections in a study that evaluated taking either tenofovir or Truvada pills as PrEP found that both worked well in women. A key difference in the second trial, called Partners PrEP, is that it involved more than 4700 couples in Kenya and Uganda in which one partner tested positive at the outset, while both VOICE and FEM-PrEP primarily enrolled young, single women. Timothy Mastro, who helped lead the truncated FEM-PrEP for FHI 360 in Durham, North Carolina, says teasing out why the same drugs would fail in one population and work in another will require analyzing two main factors: biology and behavior. Studies have shown that small amounts of antiretroviral drugs taken orally reach the vaginal mucosa. That protection may have been overwhelmed in VOICE and FEM-PrEP if male partners had higher levels of HIV than those in Partners PrEP. Or it could be that women in Partners PrEP had more motivation to "adhere" to study protocols and take pills each day as instructed, given that they knew for certain--unlike women in the other two trials--that they were having sex with an HIV-infected men. The infected men in Partners PrEP may have also encouraged their uninfected partners to adhere... Hillier emphasizes that these conflicting findings underscore that much remains to be learned about PrEP, which also worked well in gay men in yet another large study recently completed. That analysis needs to be done before public health officials roll out recommendations for its use...
The Collaboration for AIDS Vaccine Discovery, an effort backed by the Bill & Melinda Gates Foundation, has awarded $5.5 million to support a project at Northwestern University's Feinberg School of Medicine. Thomas Hope, a professor of cellular and molecular biology at the school, is studying how a vaccine could use the body's mucus as a defense against HIV. He was among the first scientists to see how HIV functions, using a technique that attaches a fluorescent molecule to the virus, and then observing it under a microscope. Hope began studying how HIV enters body tissues. "We are seeing the virus in the context of tissue, how the virus interacts with the surfaces of the female reproductive tract," Hope said. "We saw [virus] particles stuck above tissues but not entering them. They were getting caught in mucus. We got the idea that antibodies in mucus might be doing something." Hope's research will seek to develop this antibody as a vaccine. Globally, most HIV transmissions are the result of heterosexual contact. "If you can protect women, then that would sort of stop that cycle and slow down the virus and have a big impact," Hope said.
Since 2009, the numbers of youths reporting sex with a new partner without using contraception grew from 19 percent to 40 percent in France, from 38 percent to 53 percent in the United States, and from 36 percent to 43 percent in Great Britain, a new survey suggests. Undertaken on behalf of hormonal contraceptive maker Bayer HealthCare Pharmaceuticals, the survey of more than 6,000 people in 29 countries was released ahead of World Contraception Day, Sept. 26, and endorsed by 11 non-governmental reproductive health organizations. Among the report's findings:
* Just 55 percent of young people in Europe reported receiving school-based sex education, compared to 78 percent in Latin America, 76 percent in Asia Pacific, and 74 percent in the United States.
* Being too embarrassed to speak honestly with a health care professional was a major barrier to contraception, cited by 42 percent of youths lacking access in Asia Pacific, 38 percent in Europe, 27 percent in Latin America and 24 percent in United States. * Bathing or showering after sex was cited as possibly contraceptive by more than a third of Egyptian respondents.
* More than a quarter of participants in Thailand and India believed sex during menstruation was effectively contraceptive.
Under an agreement signed Monday, the UN will provide $37.8 million between now and 2015 to help Cambodia enact an HIV/AIDS prevention plan. Some 75,000 Cambodians in 60,000 households are living with HIV/AIDS, the UN Development Program estimates, of whom more than 90 percent have received antiretroviral drugs. The National AIDS Authority - whose chair, Nuth Sokhom, spoke at the signing - says it needs about $50 million a year to provide HIV drugs and educational services to prevent additional infections.
In the southern Guangxi Zhuang Autonomous Region, health workers are turning to the area's history of musical folklore to spread AIDS prevention messages. "We asked eight local singers to write and record songs about the disease," said Huang Zhanghui, who became head of Shantun village's AIDS prevention office two months ago. The traditional art form helps make the messages easier to understand and accept, Huang said. Guangxi is second only to Henan province in terms of its number of HIV infections, more than 76 percent of which are sexually transmitted, said Ge Xianmin, a Guangxi government AIDS prevention official. In addition to folk songs, Huang's office uses text messaging and public film screenings to build AIDS awareness. "We have been making progress with our anti-AIDS campaign," said Huang. "Nearly all of our villagers know how AIDS is transmitted and how to prevent it." "I used to blush at the simple mention of sexual topics," said Lu Meirong, 33, who joined a local women's AIDS group in June. Now she counsels family and relatives to avoid sex workers and use condoms, a view she urges other women in the village to adopt. "I tell them to remind their migrant relatives to be tested for HIV after returning home," she said. Peer education is critically needed in rural communities, said Wei Kaizhong, who leads the health bureau for Hechi, the administrative city of Bama County. In agreement, Ge said, "Rural residents are the weakest links in China's AIDS prevention efforts. Campaigns conducted by local residents are the most economical and effective way to stop the spread of AIDS."
Hopes for a female-controlled HIV prevention tool have been dealt a blow by the termination of one part of a large African trial after it failed to show effectiveness. The Vaginal and Oral Interventions to Control the Epidemic (VOICE) study - involving more than 5,000 HIV-negative women in South Africa, Uganda and Zimbabwe - aimed to test the safety, effectiveness and acceptability of three HIV prevention methods: a vaginal gel containing antiretroviral drug tenofovir; daily use of oral tablets containing tenofovir, and daily use of oral Truvada, a combination of tenofovir and another ARV, emtricitabine. But the independent Data and Safety Monitoring Board (DSMB) last week recommended that women assigned to the tenofovir tablet should discontinue use because the study would be unable to show a difference in effectiveness between the drug and a placebo. The trial's remaining two parts will continue as planned. "Although the findings are disappointing, this is the way research happens. By no means does it mean PrEP [pre-exposure prophylaxis] doesn't work; it just means there are many more questions to be answered, and research will continue until we get the answers," Mitchell Warren, executive director of the AIDS Vaccine Advocacy Coalition (AVAC), told IRIN/PlusNews. "This is not the end of the road, nor is it a dead end, but it is a big bump in the road."
For the investigators, the termination of the tenofovir arm is deeply disappointing, and could create challenges for the remaining two. "The fact that Truvada contains tenofovir and the gel also has the same agent means that we must work hard to communicate to our teams and participants that both arms are still viable and we are still hopeful about them," Jeanne Marrazzo, one of the trial's investigators, told IRIN/PlusNews, adding that information was being collated to ensure the trial participants were fully informed of the new developments and understood the distinction between oral tenofovir and the other two arms. The DSMB found no safety concerns with oral tenofovir. "We do not know why the oral tenofovir proved ineffective -- whether it was an adherence issue, or the absorbance of oral tenofovir did not produce high enough levels of the drug in the vagina, or a high viral load among participants' partners; we need to wait till the end of the trial to analyze all the data," she added. "We need to be careful about offering information until we have all the facts." The women on the oral tenofovir arm will all stop taking it within the next week, Marrazzo said, and they will be followed for two months to ensure there is no delayed effect.
Starting HIV therapy when a patient's immune system is still strong does not reduce the risk of AIDS or death, an international cohort study showed. But the study confirmed the current view that treatment should start when a patient's count of CD4-positive T cells falls below 350 per microliter of blood, according to Michele Jonsson Funk, PhD, of the University of North Carolina in Chapel Hill, and colleagues. And it showed slower disease progression when treatment was started with a CD4 count between 350 and 500 cells per microliter, they reported in the Sept. 26 issue of Archives of Internal Medicine. But there was little observed benefit when highly active anti-retroviral therapy (HAART) was started at CD4 counts between 500 and 800 cells per microliter. For years, guidelines suggested that HAART should start when a patient's CD4 count fell below 200 cells per microliter, or when an AIDS-defining illness occurred. But evidence remains slim about the risks and benefits of starting HAART at high CD4 counts, Jonsson Funk and colleagues noted.To help fill the gap, they analyzed outcomes for 9,455 patients enrolled in one of the 23 clinical cohorts in Europe, Australia, and Canada that are taking part in the CASCADE collaboration (for Concerted Action on SeroConversion to AIDS and Death in Europe). The researchers used a novel statistical method to create a series of sequential nested subcohorts that in essence allowed them to derive a weighted average of the benefit of starting therapy at any time within a given CD4 cell level... The primary endpoints of the analysis were the time to development of AIDS or death, pooled across subcohorts and stratified by CD4 cell count. All told, there were 52,268 person-years of follow-up from January 1996 through May 2009... While the benefits of treatment are undoubted, the timing of therapy has been controversial, according to Daniel Kuritzkes, MD, of Brigham and Women's Hospital in Cambridge, Mass. In an accompanying commentary, Kuritzkes noted that the study results are in accord with some findings of previous research but contradict others. Definitive answers will have to wait for the results of randomized trials that are now under way, he argued... While waiting for more definitive data, he concluded, the pros and cons of starting HAART at CD4 cell counts above 500 per microliter "should be weighed carefully by clinicians and patients."
US and European researchers report they have found a way to prevent HIV from damaging the immune system, possibly opening a new avenue for developing an AIDS vaccine. The scientists, led by Adriano Boasso of Imperial College London, found that HIV's attack on the immune system is thwarted if cholesterol is removed from the membrane of the virus. While infection with HIV triggers an immediate response by the innate immune system, some scientists say this response is an overreaction that weakens the next line of defense, the adaptive immune response. Once cholesterol is removed from the virus' membrane, "It's like an army that has lost its weapons but still has flags, so another army can recognize it and attack it," Boasso said. "HIV is very sneaky," Boasso continued. "It evades the host's defenses 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, Boasso said, may be why the hunt for an AIDS vaccine has proven so vexing. "Most vaccines prime the adaptive response to recognize 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 it infects, the authors wrote. The cholesterol in the membrane helps it stay fluid and able to interact with certain types of cells. Immune cells called plasmacytoid dendritic cells (pDCs) normally recognize HIV and quickly produce signaling molecules, or interferons. These switch on various processes that, while initially helpful, damage the immune system if they stay activated for too long. If the cholesterol is removed from HIV's envelope, the team discovered, pDCs are not activated, leaving T cells free to mount an adaptive response and fight the virus more effectively. The study, "Over-Activation of Plasmacytoid Dendritic Cell Inhibits Anti-Viral T-Cell Responses: A Model for HIV Immunopathogenesis," was published in Blood.
Modelling has demonstrated the benefits and now data has provided the proof as researchers in Haiti have found that earlier HIV treatment is cost-effective, reducing the risk of death by 75 percent among HIV patients for just US$6.25 more a month. In 2009, researchers released the results of a then unpublished Haitian clinical trial. Conducted among 800 HIV patients, the study showed that those who received antiretrovirals (ARVs) when their immune systems were stronger - at higher CD4 counts of 200 to 350 - were less likely to die than their peers who waited until their CD4 counts fell to 200. About five months later, the World Health Organization (WHO) issued new HIV treatment guidelines that advised countries to start HIV patients on treatment at a new higher CD4 count of 350 instead of 200. Now those researchers have released the world's first and possibly only cost-effectiveness study on earlier HIV treatment tied to a randomized clinical trial. Published in the September 2011 edition of the medical journal, PLoS Medicine, the study is based on data from the original Haitian study that allowed researchers to calculate costs associated with the first three years of earlier treatment - including everything from drug and family caregiver costs to subsidies for patient transport to and from the clinic. Bruce Schackman, associate professor of public health at the US Weill Cornell Medical College and a co-author of the study, said this was probably the first and last research of its kind. Given the overwhelming evidence for early treatment, duplicating the study now would be unethical, he said. "This was a unique opportunity to do this kind of research," Schackman told IRIN/PlusNews. "I don't think we'd be able to do a similar comparison [study] given the compelling mortality gain we've seen with early treatment." And although cost effectiveness is relative, Schackman said he believed the findings were applicable to other countries... He added that some countries with higher healthcare costs than Haiti might see an even greater degree of cost-effectiveness..."This study is so important because the US government pays a lot of money for HIV treatment and... right now there's a committee in Congress that is trying to cut millions in foreign aid," said lead author Serena Koenig. "Our ability to treat people in resource-poor settings depends greatly on how much it costs." ...Both authors said they hoped their findings would help more developing countries move towards adopting earlier treatment - and donors commit to supporting this...
A new computational approach has predicted numerous human proteins that the human immunodeficiency virus (HIV) requires to replicate itself. These discoveries "constitute a powerful resource for experimentalists who desire to discover new targets for human proteins that can control the spread of HIV," according to the authors of this study that appears in the Sept. 22, 2011 issue of PLoS Computational Biology... A recent line of research is examining whether human proteins can be targeted to cure HIV. Since viruses such as HIV have very small genomes, they must exploit the cellular machinery of the host to spread. Therefore, disrupting the activity of selected host proteins may impede viruses. Moreover, since human proteins evolve at a much slower rate than HIV proteins, human proteins that are targeted by drugs are very unlikely to develop mutations that render the drugs ineffective. In fact, three studies published in 2008 systematically silenced virtually every human gene in order to discover HIV Dependency Factors (HDFs), i.e., those genes that are necessary for HIV to survive and replicate. Each of these three studies discovered hundreds of HDFs. However, a puzzling aspect was that only a handful of HDFs were common to two or more experiments. "We set out to untangle this mystery," Murali said. "We hypothesized that many HDFs have not yet been discovered. Other papers had suggested that HDFs may themselves interact with each other. Inspired by these observations, we hypothesized that we could predict new HDFs by exploiting the proximity between HDFs within networks of interactions between human proteins." To this end, they used an algorithm called SinkSource developed by Murali and Tyler. "We found that SinkSource and one of its variants made predictions of very high quality," Murali added. "We evaluated predicted HDFS using a number of additional datasets that we did not use during the prediction step." From these results, Murali, Tyler, and Katze concluded that existing genomic screens are "incomplete and many HDFs are yet to be discovered experimentally. Our results suggest that many HDFs are yet to be discovered and that they have potential value as prognostic markers to determine pathological outcome and the likelihood of Acquired Immune Deficiency Syndrome (AIDS) development."
Abstract Background: Loss to follow-up of HIV-positive patients before initiation of antiretroviral therapy can exceed 50% in low-income settings and is a challenge to the scale-up of treatment. We implemented point-of-care counting of CD4 cells in Mozambique and assessed the effect on loss to follow-up before immunological staging and treatment initiation.
Methods: In this observational cohort study, data for enrolment into HIV management and initiation of antiretroviral therapy were extracted retrospectively from patients' records at four primary health clinics providing HIV treatment and point-of-care CD4 services. Loss to follow-up and the duration of each preparatory step before treatment initiation were measured and compared with baseline data from before the introduction of point-of-care CD4 testing.
Findings: After the introduction of point-of-care CD4 the proportion of patients lost to follow-up before completion of CD4 staging dropped from 57% (278 of 492) to 21% (92 of 437) (adjusted odds ratio [OR] 0.2, 95% CI 0.15-0.27). Total loss to follow-up before initiation of antiretroviral treatment fell from 64% (314 of 492) to 33% (142 of 437) (OR 0.27, 95% CI 0.21-0.36) and the proportion of enrolled patients initiating antiretroviral therapy increased from 12% (57 of 492) to 22% (94 of 437) (OR 2.05, 95% CI 1.42-2.96). The median time from enrolment to antiretroviral therapy initiation reduced from 48 days to 20 days (p<0.0001), primarily because of a reduction in the median time taken to complete CD4 staging, which decreased from 32 days to 3 days (p<0.0001). Loss to follow-up between staging and antiretroviral therapy initiation did not change significantly (OR 0.84, 95% CI 0.49-1.45).
Interpretation: Point-of-care CD4 testing enabled clinics to stage patients rapidly on-site after enrolment, which reduced opportunities for pretreatment loss to follow-up. As a result, more patients were identified as eligible for and initiated antiretroviral treatment. Point-of-care testing might therefore be an effective intervention to reduce pretreatment loss to follow-up.
HSV-2, the primary causative agent of genital herpes, establishes latency in sensory ganglia and reactivates causing recurrent lesions and viral shedding. Induction or expansion of CD4+ and CD8+ T cell responses are expected to be important for a successful therapeutic vaccine against HSV-2. A candidate vaccine consisting of 32 synthetic 35mer HSV-2 peptides non-covalently complexed with recombinant human Hsc70 protein (named HerpV, formerly AG-707) was tested for safety and immunogenicity in a Phase I study. These peptides are derived from 22 HSV-2 proteins representative of all phases of viral replication. Thirty-seven HSV-2 infected participants were randomized to one of four treatment cohorts: HerpV + QS-21 (saponin adjuvant), HerpV, QS-21, or vehicle. The vaccine was well tolerated and safe. All seven participants with evaluable samples who were administered HerpV with QS-21 demonstrated a statistically significant CD4+ T cell response to HSV-2 antigens, and the majority of such participants demonstrated a statistically significant CD8+ T cell response as well. To our knowledge, this is the first candidate vaccine against HSV-2 to demonstrate a broad CD4+ and CD8+ T cell response in HSV-2+ participants, and the first HSP-based vaccine to show immune responses against viral antigens in humans.
Efforts to develop a subunit vaccine against genital herpes have been hampered by lack of knowledge of the protective antigens of HSV-2, the causative agent of the disease. Vaccines based either on selected antigens or attenuated live virus approaches have not demonstrated meaningful clinical activity. We present here results of a therapeutic vaccine candidate, HerpV (formerly called AG-707), consisting of 32 HSV-2 peptides derived from 22 HSV-2 proteins, complexed non-covalently to the HSP70 chaperone and formulated with QS-21 saponin adjuvant. HerpV is observed to be immunogenic, generating CD4+ and CD8+ T cell responses in three mouse strains including HLA-A2 transgenic mice. Optimal T cell stimulation was dependent on the synergistic adjuvant properties of QS-21 with hsp70. The vaccine provided significant protection from viral challenge in a mouse prophylaxis model and showed signals of activity in a guinea pig therapeutic model of existing infection. Peripheral blood mononuclear cells from human HSV-2+ subjects also showed reactivity in vitro to a subset of individual peptides and to the pool of all 32 peptides. Recombinant human Hsc70 complexed with the 32 peptides also stimulated the expansion of CD8+ T cells from HSV-2+ subjects in vitro. These studies demonstrate that HerpV is a promising immunotherapy candidate for genital herpes, and provide a foundation for evaluating HerpV in human HSV-2+ subjects with the intent of eliciting CD4+ and CD8+ T cell responses to a broad array of viral antigens.
An urgent need exists for HIV-1 microbicides. Here, we describe the in vivo testing of lactic acid bacteria bioengineered to secrete cyanovirin-N. We fed pigtail macaques a yogurt formulation that used bioengineered strains as a starter culture. Cyanovirin-N expression could be detected in the rectal vault during and immediately after feeding. Ex vivo viral challenge of rectal tissue biopsies revealed that peak viral burden was significantly lower in tissue obtained from experimental animals compared to control animals. Formulation of candidate compounds in lactic acid bacteria and their oral administration appears to be a feasible strategy for mucosal delivery of microbicides.
Samson Muchina Kinyanjui and colleagues from the KEMRI-Wellcome Trust Research Programme discuss how they modified their informed consent processes by taking into account local social, cultural, and economic contexts in the design and administration of consent forms.
HIV testing is a key component of prevention and an entry point into HIV/AIDS treatment and care however, coverage and access to testing remains low in Uganda. Home-Based HIV Counseling and Testing (HBHCT) has potential to increase access and early identification of unknown HIV/AIDS disease. This study investigated the level of acceptance of Home-Based HIV Counseling and Testing (HBHCT),the HIV sero-prevalence and the factors associated with acceptance of HBHCT in an urban setting.
A cross-sectional house-to-house survey was conducted in Rubaga division of Kampala from January -June 2009. Residents aged [greater than or equal to]15 years were interviewed and tested for HIV by trained nurse-counselors using the national standard guidelines. Acceptance of HBHCT was defined as consenting, taking the HIV test and receipt of results offered during the home visit. Multivariable logistic regression analysis was performed to determine significant factors associated with acceptance of HBHCT.
We enrolled 588 participants, 408 (69%, 95% CI: 66%-73%) accepted testing. After adjusting for confounding, being male (adj. OR 1.65; 95%CI 1.03, 2.73), age 25-34 (adj. OR 0.63; 95% CI 0.40, 0.94) and [greater than or equal to]35years (adj. OR 0.30; 95%CI 0.17, 0.56), being previously married (adj. OR 3.22; 95%CI 1.49, 6.98) and previous HIV testing (adj. OR 0.50; 95%CI 0.30, 0.74) were significantly associated with HBHCT acceptance. Of 408 who took the test, 30 (7.4%, 95% CI: 4.8%- 9.9%) previously unknown HIV positive individuals were identified and linked to care.
Acceptance of home-based counseling and testing was relatively high in this urban setting. This strategy provided access to HIV testing for previously untested and unknown HIV-infected individuals in the community. Age, sex, marital status and previous HIV test history are important factors that may be considered when designing programs for home-based HIV testing in urban settings in Uganda.