21 MAY 2010, VOLUME 11, ISSUE 17

Stakeholders at the just concluded 5th National HIV & AIDS conference have called for immediate scaling up of HIV prevention strategies, saying it is the only way the fight against the disease could be won. The 4-day conference, which was organized by Network for HIV & AIDS Research in Nigeria (NARN) in partnership with the National Agency for the Control of AIDS (NACA), with support from the United Nations system, the US Government, other developmental partners and civil society organisations believed that if prevention is prioritised, the spread of HIV would be controlled to the barest minimum.

In one of the sessions organized by the United Nations Development Fund for Women (UNIFEM) in collaboration with United National Development Programme (UNDP), Prof. Dennis Ityavyar the UNIFEM Research Consultant on Gender and HIV, outlined the status of women within the national response and highlighted the key determinants of HIV transmission in the context of culture and socio- economic issues. According to him, "Cultural practices have a fundamental role to play in HIV prevention, Prevention of Mother-to-Child Transmission (PMTCT) and male involvement in reproductive health services. A number of commonly observed traditional practices are now recognized as being directly responsible for the spread of HIV & AIDS".

On his first full day in office, President Barack Obama issued a memorandum calling for "creating an unprecedented level of openness in Government." The Department of Health and Human Services embraced this goal, and in June 2009, the new commissioner of the Food and Drug Administration (FDA), Dr. Margaret Hamburg, announced a major transparency initiative. The goal of this initiative was to better explain the FDA's actions by providing information that supports clinical medicine, biomedical innovation, and public health.

The FDA already makes substantial amounts of information about the regulatory process for medical products publicly available. For example, extensive summary data on drugs and devices are released for public advisory committee meetings before approval, and detailed reviews of drugs are released after approval. However, many aspects of the FDA's work remain unknown to the public. Few people understand the basic processes followed within the FDA, such as how the agency monitors medical products for safety after they have been approved or how the device-approval process works for products in various risk categories.

When Nobel laureate Francoise Barre-Sinoussi and her colleagues set out in the early 1980s to isolate the virus that causes AIDS, the odds were against them. "This was not a good situation, to try to locate a virus from nothing," Barre-Sinoussi told a conference of HIV experts Friday at the 19th Canadian Conference on HIV/AIDS in Saskatoon.

Along with her colleague, Luc Montagnier, at the Institut Pasteur in Paris, she succeeded in isolating the virus in 1983. By then, reports of deaths among people with severe immune deficiency were appearing all over the world, among men, women and children -- AIDS had gone global. By 1985, with the help of private research companies, they managed to create the first diagnostic tests for the virus. Fighting the spread of HIV became her only focus. "We had to stop immediately our other research programs," she said. "We knew it would be a lot of work."

Ugandan AIDS activists have expressed concern over a decision by the Ministry of Health to back an HIV/AIDS bill that would criminalize the deliberate transmission of HIV. Last week, State Minister for Health in charge of General Duties, Richard Nduhura, appeared before the parliamentary committee on HIV to explain the government's position on the HIV and AIDS Prevention and Control Bill (2009). Nduhura backtracked on his earlier position that portions of the bill would lead to discrimination and undermine the rights of people living with HIV. "I am in support of the law as it is now," he told IRIN/PlusNews.

Uganda's President Yoweri Museveni has in the past stated that he "fully supports" an HIV/AIDS law that would criminalize deliberate transmission of the virus. The bill, as well as another controversial proposed law, the Anti-Homosexuality Bill 2009, has led to widespread criticism by human rights activists.

According to Stella Kentutsi, of the National Forum of People Living with AIDS Network in Uganda, the minister's U-turn showed there was still a lack of understanding of its clauses and how they would affect people living with HIV. "The biggest problem we have with this bill is lack of awareness; we think [Nduhura's] comments were biased and influenced by parliament," she said. "He needs to sit and think carefully, then make a decision that will balance both sides."

Canada must do more to help prevent the spread of HIV throughout the world, an expert told a national HIV/AIDS conference Sunday. Dr. Allan Ronald, who received a lifetime achievement award at the Canadian Association for HIV Researchers conference, said Canada is lagging behind other countries in helping developing nations battle the deadly disease. "We can really rapidly increase our contribution," said the internal medicine and infectious disease specialist. About 500 people attended the weekend conference in Saskatoon.

Ronald, who has spent much of the last 10 years working in Uganda with the Academic Alliance for AIDS Care and Prevention in Africa, said there is much more work to be done to prevent the spread of HIV. "There is still no unified strategy for HIV prevention ... We can't just take two or three pieces - and push circumcision or push condom use - we need them all and they need to be well understood," he said Sunday. The Canadian International Development Agency spends $100 million to $142 million annually on international HIV/AIDS programs, but that should increase to $500 million by 2014, Ronald said.

Health care professionals credit biomedical research using animals with any number of A-list therapies -- some relieve pain, others save lives. And yet, critics charge the research isn't as useful as it could, or even should, be. And some feel it's flatly unethical.

Inside the Wisconsin National Primate Research Center at the University of Wisconsin-Madison, some 250 scientists conduct experiments using more than 1,400 monkeys of three species: Cynomolgus and Rhesus Macaques, and Common Marmosets. While not everyone agrees with the work, researchers like Dave O'Connor have dedicated their lives to it. "It's 2 million people a year who are becoming newly infected with HIV, 2 million. And these are people who have mothers, they're fathers. It's leaving an entire generation of orphans in Africa," O'Connor said.

The AIDS Vaccine Research Laboratory where O'Connor works is a busy and high-tech place, funded through a mix of federal grants and private gifts, including major contributions from the Bill & Melinda Gates Foundation. It's designed to help develop a vaccine to prevent the transmission of HIV/AIDS, a collaborative effort that he shares with two other researchers in the building.

Specifically O'Connor studies the immune system and how it reacts to the virus, which is known as SIV, or Simian Immunodeficiency Virus, in monkeys. "They're genetic cousins. They're very closely related to one another and by infecting non-human primates with these SIV strains, we have the ability to monitor the first few weeks of infection," said O'Connor.

May 17 is the International Day Against Homophobia. Homophobia is considered one of the main obstacles in implementing HIV prevention strategies. Of the 192 member states of the United Nations, 85 have laws that still criminalize homosexual behaviour and, in some of these countries, conviction can even result in the death penalty.

Speaking on the occasion, UNAIDS Executive Director Michel Sidibe said, "I urge all governments to take steps to eliminate stigma and discrimination faced by men who have sex with men, lesbians and transgender populations. They must also create social and legal environments that ensure respect for human rights and enable universal access to HIV prevention, treatment, care and support."

A campaign is being launched to try to enlist public support to ensure no more children are born with HIV by 2015. It is the work of the Global Fund, which uses donations from governments to fight HIV, TB and malaria. The Born HIV Free campaign comes at a critical time, with the fund seeking donations of up to $20bn over the next three years. It recognises this will be a battle, as governments deal with the aftermath of the Greek financial crisis.

HIV can be passed from mother to child during pregnancy, labour or breast-feeding. This type of transmission has been almost wiped out in countries such as the UK, because pregnant women who test positive for the virus that causes AIDS can be treated with drugs. Other measures -- such as giving birth by caesarian section -- help stop HIV being transmitted to the baby. But in developing countries, 430,000 children are born with HIV every year.

The number of people on anti-retroviral therapy has increased from 67,525 in 2005, to 200,213 in 2009, MPs have noted. In a report to Parliament yesterday, MPs on the HIV/AIDS committee said there has been significant progress in the provision of treatment and care for people living with HIV/AIDS since 2005. The committee chairperson, Beatrice Rwakimari, attributed the improvement to increased support by donors. She, however, warned that given the rate of new infections and the corresponding budget for HIV/AIDS programmes, more people are likely not to access treatment.

According to the Ministry of Health statistics, over 100,000 new infections occurs annually, while about 1.1m people are living with the disease, half of these not on antiretroviral therapy. The figures also indicate that sexual transmission contributes to 76% of the new infections, while mother-to- child accounts for 22%. "It is unfortunate that almost half of the people eligible for antiretroviral drugs (ARVs) cannot access treatment. Medical supplies and health service providers are inadequate. As a result, a large section of the population finds it hard to access health services," Rwakimari said while presenting the committee report on the national response to the epidemic.

Initiative seeks billions of dollars to develop promising drugs and vaccines.

Despite decades of research into drugs and vaccines for neglected diseases such as tuberculosis and dengue fever, few products have made it through clinical development and into the hands of the millions who desperately need them. One of the biggest hurdles is the sheer expense of running clinical trials, compared with the small profits that commercial companies can expect to make from treatments for diseases that disproportionately affect poor and marginalized populations.

This week, alongside the World Health Organization's (WHO's) annual assembly of health ministers in Geneva, Switzerland, a consortium of industry and non-governmental organizations proposed a scheme to help address the problem: a global fund that would channel billions of dollars a year into product development. Plans for the fund were put forward by the International AIDS Vaccine Initiative (IAVI), the pharmaceutical giant Novartis and the George Institute for International Health in Sydney, Australia. It would channel money from donors towards product-development partnerships (PDPs) -- collaborative efforts between research agencies, donors and biotech and pharmaceutical companies to develop drugs, diagnostics and vaccines for the developing world. The fund aims to encourage contributions from donors who lack the resources or expertise to assess the quality and progress of the various PDP offerings.

Dozens of not-for-profit PDPs, including the IAVI, the Medicines for Malaria Venture, the Global Alliance for TB Drug Development, and the Drugs for Neglected Diseases initiative (DNDi), have been set up during the past 15 years. Their aim is to bridge the gap between basic research and product development, and to prevent promising research leads for neglected diseases from languishing on the shelf. They are run like businesses, but are supported by donor funding, and have generous intellectual-property rules to make any products affordable to poor countries, allowing generic manufacturers to make cheap versions freely.

See commentary from James Love, Director, Knowledge Ecology International: PDP+ presented at WHA to skeptical audience

Try after try to make vaginal creams that could repel the AIDS virus have failed. Now researchers are testing if a drug used to treat HIV infection finally might give women a tool to prevent it -- by infusing the medicine into vaginal gels and contraceptive-style rings. Even quick-dissolving anti-HIV films are being created, the same style now used for breath-fresheners or allergy medicines but made for fingertip application in the vagina. Called microbicides, this kind of woman-controlled protection is considered key to battling the HIV epidemic -- especially in developing countries where the virus is at its worst and women too often can't get their partners to use a condom.

For two decades, scientists tried less powerful medications in disappointing microbicide attempts. Results from the first study to see if this new strategy works -- South African women tested a gel made of the AIDS drug tenofovir -- aren't due until July. But researchers gathering for the biennial International Microbicides Conference in Pittsburgh next weekend express cautious optimism.

"Frankly, blocking transmission of the virus appears to be a lot harder than anyone understood it would be at the beginning," says meeting co-chair Dr. Sharon Hillier of the University of Pittsburgh and a principal investigator of the Microbicide Trials Network. "The reason we're not depressed in the microbicide world? We actually have learned a lot and moved on to think about potent drugs and really cool delivery methods."

Antiretroviral drugs have revolutionized AIDS care, helping people live far longer with the virus. They've also successfully lowered the risk that an infected pregnant woman passes HIV to her child. So it was logical for scientists to begin testing whether swallowing an antiretroviral drug every day could protect the still healthy, both men and women, from getting infected. More than half a dozen studies of this so-called pre-exposure prophylaxis are under way among high-risk populations around the world, largely using the drug tenofovir because it tends to cause fewer side effects than many other AIDS drugs.

Each year on May 18, people around the world commemorate HIV Vaccine Awareness Day. This is done to recognise and thank the thousands of volunteers, community members, health professionals, researchers and scientists who are working together to find a safe and effective HIV vaccine. People who volunteer to participate in clinical trials of AIDS vaccines and other new HIV prevention approaches have often been hailed as the heroes in the fight against the HIV/AIDS epidemic. Besides the risks and responsibilities they shoulder for the benefit of humanity, they win many auxiliary benefits for their communities.

For communities that have been devastated by HIV/AIDS, every research comes with new hope. To date, none of the research clinical trials conducted so far has delivered an effective product, be it an HIV vaccine, microbicide, or post-exposure prophylaxis (PEP, the use of ARVs for prevention). Participants and their communities have had to deal with the burden of disappointing results, save for medical male circumcision, which showed a 60% reduction in the risk of infection in men.

HIV prevention clinical trials use various approaches to involve communities as part of the ethical requirements, but also in order to recruit research participants and to create a partnership to facilitate the successful conduct of the research. Researchers often use various approaches to recruit participants. Most trials recruit through existing health centres, and also use the same facilities during the follow-up of participants. This approach usually calls for additional investments in facilities at the participating health centres.

For example, through the microbicide trial that ended in Masaka last year, some health centres were renovated, medicines supplied and health staff trained. Trials often employ many people in various capacities, including the investigators, support staff and field mobilisers. Up to 100 people for instance were involved in community education and voluntary counselling and testing (VCT) which took place as part of the process of preparing the community in Masaka for the research and recruitment of volunteers.

The worldwide eradication of smallpox may, inadvertently, have helped spread HIV infection, scientists believe.

Experts say the vaccine used to wipe out smallpox offered some protection against the Aids virus and, now it is no longer used, HIV has flourished. The US investigators said trials indicated the smallpox jab interferes with how well HIV multiplies. But they say in the journal BMC Immunology it is too early to recommend smallpox vaccine for fighting HIV.

Lead researcher Dr Raymond Weinstein, from Virginia's George Mason University, said: "There have been several proposed explanations for the rapid spread of HIV in Africa, including wars, the reuse of unsterilised needles and the contamination of early batches of polio vaccine. "However, all of these have been either disproved or do not sufficiently explain the behaviour of the HIV pandemic."

Dr Weinstein and his colleagues believe immunisation against smallpox may go some way to explain the recent rises in HIV prevalence. Smallpox immunisation was gradually withdrawn from the 1950s to the 1970s, following the worldwide eradication of the disease, and HIV has been spreading exponentially since then, they say. Now, only scientists and medical professionals working with smallpox are vaccinated.

To test if the events may be linked, the researchers looked at the white blood cells taken from people recently immunised against smallpox and tested how they responded to HIV. They found significantly lower replication rates of HIV in blood cells from vaccinated individuals, compared with those from unvaccinated controls. The smallpox vaccine appeared to cut HIV replication five-fold.

To view the study in BMC Immunology, click here.

May 18, is World Vaccine Awareness Day. Uganda was home to the first-ever HIV vaccine trial in Africa in 1995, which was conducted at the Joint Clinical Research Centre. Since that time, Uganda has remained an important contributor to HIV vaccine research and development. HIV Vaccine Awareness Day provides a great opportunity to thank people who are helping find an effective vaccine. These include the clinical trial volunteers, health professionals, community members and the researchers. It is also an opportunity to learn more about vaccine research.

An AIDS vaccine is described as the best hope for ending the spread of HIV. Dr Annet Nanvubya of Uganda Virus Research Institute (UVRI), Entebbe, says an effective AIDS vaccine will protect people from acquiring HIV and prevent or slow down the rate at which those who are already infected can progress to AIDS. Although many trials have been done worldwide and produced no vaccine approved for use to date, great strides have been made. Every time a trial has stopped, there are discoveries, new information and developments that take researchers closer to discovering the vaccine.

Today, 7,500 people will get infected by HIV, the virus that leads to AIDS, which has no cure. Over 300 of these will be Ugandans. That is, on average, around 13 people per hour. Eight of these will most likely be women. These calculations are based on the 2010 statistics from Uganda AIDS Commission survey. According to the data, of the 301 unfortunate citizens, only 178 people have a realistic chance of receiving free HIV drugs (ARVs), if the current situation remains as is. But all indicators show the situation is deteriorating.

For every two people put on ARVs, five others get infected with HIV. And according to the Medicins San Frontiers' report, many people living with HIV and on treatment are routinely turned away at major clinics because there are no drugs. Treatment programmes in many African countries are not enrolling more people on ARVs. It could be the global recession, the change of focus to cheaper diseases which are killing more people, or donor fatigue. Whatever it is, Uganda will not manage the increasing HIV burden if the rates of infection are not curbed. According to the head of the Uganda AIDS Commission, Dr. Kihumuro Apuuli, it is impossible to be effective mopping the floor if the tap is not switched off. Apuuli says there is need for an effective preventive technology to close the tap.

Dr. Patrick Ndase, Africa's Regional physician in international clinical research on HIV, said infection can be stopped at three different spots. Before exposure, at the point of transmission and after infection.

The United States in collaboration with the Tanzanian government Monday announced the establishment of the first Medication Assisted Therapy (MAT) programme for drug users in sub-Saharan Africa, a crucial part of HIV control that allows addicts to return to a regular, productive and healthier life. Unveiling the programme here Monday, US Ambassador Alfonso E. Lenhardt, US Global AIDS Coordinator Ambassador Eric Goosby and Tanzania's Minister of State in Prime Minister's Office Phillip Marmo said the services would be initiated shortly in Dar es Salaam and Zanzibar.

At the same ceremony, Tanzania Drug Control Commission (DCC) in collaboration with PEPFAR Tanzania also made public five documents that will serve as the blueprint for Tanzania's response to HIV among drug users. As the first country in sub-Saharan Africa to introduce MAT, Tanzania will serve as a model as well as a public health leader in the field of HIV prevention.

HIV prevalence among gay and bisexual men has hit alarming levels in Asia and most of them do not have access to services and care due to punitive laws which drive them underground, a U.N.-backed report said on Monday. The situation may worsen if countries fail to reverse laws that criminalize sex between adult males and cross-dressing, and selectively prosecute gay and bisexual men using public order and prostitution offences, it added.

"Nineteen of 48 countries in the Asia Pacific region criminalize male-to-male sex, and these laws often take on the force of vigilantism, often leading to abuse and human rights violations," according to the report. "Even where there are no specific offences for male-to-male sex, MSM (men who have sex with men) and transgender people are subject to police abuses and are targeted by police for other offences relating to public order, vagrancy, prostitution and obscenity."

Put together by the United Nations Development Programme (UNDP), Asia Pacific Coalition on Male Sexual Health (APCPM) and the University of Hong Kong's Center for Comparative and Public Law, the report said HIV prevalence among gay and bisexual men has been rising in many Asian countries. For example, HIV prevalence among gay and bisexual men in Bangkok was now 30.8 percent compared to 1.4 percent in the adult population in Thailand. In Yangon, the figure was 29.3 percent versus 0.7 percent in Myanmar; while in Mumbai, it was 17 percent versus 0.36 percent in all of India.

Over 90 percent of gay and bisexual men in Asia do not have access to HIV prevention and care services, the report said. It cited examples of repressive laws or lack of anti-discrimination laws preventing these men from getting the help they needed. These include HIV prevention services being interrupted by police harassment of outreach workers, many of whom are MSM or transgender peer educators. Condoms and lubricants are also confiscated by police as evidence of sex work or of illegal male-to-male sex.

See related press release: Punitive and Discriminatory Laws limit access to HIV prevention and care services for men having sex with men in Asia Pacific

We need to re-ring the alarm about HIV transmission among gay and bisexual men. In March, the Centers for Disease Control and Prevention released statistics showing significant disparities between rates of HIV and syphilis infection among men who have sex with men and the rest of the US population.

Men who have sex with men are 44 times more likely to contract HIV than other men and 40 times more likely to contract HIV than women. They are 46 times more likely to contract syphilis than other men and 71 times more likely than women.

After miracle breakthroughs in treatment and two decades worth of increasingly sophisticated understanding about sexually transmitted diseases, how did we end up back at the beginning with gay and bisexual men so vulnerable to infection?

We're here because we've watered down prevention messages. Explicit public campaigns about how to stay safe have been replaced with simplistic messages about condoms. If we have learned anything about preventing HIV transmission among gay and bisexual men in the last 25 year we've learned this: it's not about condoms; it's about dignity. As long as men who have sex with men are at a higher risk for mental illness, trauma, and substance abuse -- which they are thanks in large part to the stigma attached to being gay or engaging in gay sex -- they are going to be more likely to engage in risky behaviors.

Community health and prevention measures like safe injection sites? Vaccine delivery initiatives? International AIDS programs? Basic research? Having seen the flagship initiative of Canada's long-term HIV vaccine strategy blasted out of existence with the cancellation of plans to construct a pilot lot manufacturing facility in Winnipeg, Manitoba, Canadian researchers and AIDS activists have a raft of views on how the government should repurpose the $88 million once ticketed for the initiative.

Anxious about how the government might spend that money, some are even calling for national consultations on a suitable plan to spend the money and ensure that Canada can adequately exploit fruits from the labour of the country's AIDS and HIV vaccine research community. For its part, though, the government is holding its cards close to its chest. The Public Health Agency of Canada, which oversees how monies will be spent under the $137 million Canadian HIV Vaccine Initiative, says it likely won't make a decision until the fall.

"We're actively working on this," says Dr. Rainier Engelhardt, PHAC's assistant deputy minister of infectious diseases and emergency preparedness. "It's certainly not years. We're talking about the next few months." But all the options under consideration will make a contribution to finding or preparing for an HIV vaccine, Engelhardt says.

Editor's note: This article was second in a series. Also see: Part I: Squabble continues over cancellation of HIV vaccine facility (CMAJ 2010. DOI:10.1503/cmaj.109-3255)

The idea doesn't sound complicated: Make one virus able to kill another. Liu Chang, a 28-year-old instructor with medical school of Nankai University in Tiajin, proposes to create a virus in the lab that could kill HIV, the virus causing the deadly AIDS, which kills people worldwide. His idea helped him win a $100,000 research grant from Grand Challenges Explorations, part of the Grand Challenges in Global Health initiative supported by the Gates Foundation. The initiative is a five-year, $100 million program to promote innovation in global health.

"It's big pleasant surprise for me to get the grant supporting my research, which might one day help save AIDS victims," Liu said Wednesday. "In China, the chance for a young researcher like me, with no background of overseas study, to get a grant of this sum is quite slim," he said. The grant money has already been distributed and his award-winning proposal project, "HIVi: a novel weapon to kill HIV," is underway. If the research passes an expert evaluation one year from now, he would get another $1,000,000 to support further work.

Among the 78 awards of $100,000 in the forth round of the Grand Challenges grants announced by the foundation May 11, two are from China. In addition to Liu, the other is Professor Dang Hongyue with the China University of Petroleum in Qingdao. Dang will research whether early-stage pneumonia infection produces specific biomarkers that can be detected in a breath analysis.

Vaccines have made possible some of the greatest public health successes of the past century. Immunisation helps avert an estimated 2.5 million child deaths each year, as well as millions more bouts of illness and disability. Poor countries as well as rich have benefited, although developing countries almost always benefit only after long delays. Basic childhood immunisation is one of the few health interventions to which most of the world's poor have access, free of charge and through the public sector. In fact, immunisation is one of the most equitable health interventions, protecting girls and boys alike, and reaching the poor within countries at higher rates relative to the wealthy than other services.

Despite their impact, vaccines have generally received less attention than drugs. But the vaccine landscape is shifting, and new opportunities, challenges, and debates have pushed vaccines to the centre of global health discussions. The issues are complex and the experience gained in the struggle for access to HIV medications is an imperfect guide. The basic principles -- equitable access and research and development (R&D) based on needs -- are the same, but vaccines differ from drugs in important ways.

There are multiple factors that make delivering vaccines to children in developing countries difficult. These include -- among others -- high prices of newer vaccines, the lack of R&D for better-adapted and needed vaccines, as well as weak health systems with corresponding health worker shortages. This paper will focus on the first two points, outlining some of the major issues and exploring possible solutions.

Africa has long borne the brunt of the Aids pandemic. The disease has spread across sub-Saharan Africa at an alarming rate, leaving in its wake millions of orphans, felling men and women in their most productive years and rendering countless families destitute. Yet, as we mark this year's World Aids Vaccine Day on May 18, we have more reason than ever to be hopeful that we will have the tools in hand to reverse the spread of HIV.

Over recent months, scientists have reported several advances in Aids vaccine research and development. Last November, researchers established for the first time that an Aids vaccine can reduce the risk of HIV infection in humans: the results of the largest Aids vaccine trial ever conducted revealed that a combination of two experimental vaccines given to volunteers in Thailand provided modest protection against HIV.

In September, the International Aids Vaccine Initiative and its partners around the world announced the isolation of two new broadly neutralising antibodies against HIV, which were both identified from a single volunteer in Africa with the support of African researchers. These antibodies reveal a vulnerability of HIV that vaccine designers may find easier to exploit than any hitherto identified. Adding to this good news, researchers at the National Institutes of Health subsequently reported the discovery of a third such antibody.

But much work lies ahead. Researchers will, for example, now have to carefully study the newly discovered antibodies and figure out how to elicit similar antibodies in people to protect them from HIV infection. Similarly, researchers will now explore the data from the Thai study to better understand how a more effective Aids vaccine must work.

The Government should support alternative ways of preventing the spread of HIV/AIDS, the director general of the Uganda AIDS Commission, Dr. Kihumuro Apuuli, has urged. "While a lot of money is spent on treating the infected, funding for preventive initiatives like the research on Microbicides gets lesser," he said on Thursday during a key stakeholders meeting by the Makerere University - John Hopkins University research collaboration. Microbicides are gels applied into the vagina before sex to kill bacteria and viruses like HIV on contact.

However, they have worked in the laboratory and on animals. Research is now being carried out to determine whether they can also work in humans. Addressing a team of MPs representing the HIV parliamentary committee, Kihumuro said: "Prevention might be the way to beat this biggest challenge mankind has ever faced, and the research on Microbicides is a big step towards achieving that."

Researchers said although earlier microbicide researches were not effective, another by the Microbicide Trials Network (MTN), could be successful because the Microbicides being used are ARV-based. Dr. Clemesia Nakabiito, MTN's principal investigator, said: "Microbicides made out of ARVs might be the solution."

Dr Aaron Motsoaledi, appointed South Africa's Health Minister about a year ago, is in charge of the world's largest antiretroviral (ARV) treatment programme. Many AIDS activists credit him with helping to usher in a new approach to HIV and AIDS, including changes to treatment guidelines announced by President Jacob Zuma on World AIDS Day 2009. Can the government deliver? IRIN/PlusNews spoke to the minister to find out.

Question: Your target is to test about 15 million South Africans by 2011. What is the point of scaling up testing when the country's treatment capacity is still lagging?
Answer: Our treatment capacity has been markedly boosted since the president's announcement on World AIDS Day. We have increased our [health] budget from the previous financial year [March 2009 to February 2010] ... there's a difference of 33 percent, which is the biggest budgetary increase in any item in the budget. When you are [HIV-]positive, you don't only gain from treatment, you also gain from a change of lifestyle. Some may not need treatment but they will know through the HIV testing and counselling (HCT) campaign that they are positive, and may start attending sessions about how they should change their lifestyle and how they should live.

Q: President Zuma has made some significant changes to HIV treatment guidelines to make more people eligible for treatment. Can the country afford it?
A: The new changes are the ones that caused the budget to increase by 33 percent, and Treasury has been able to make that money available, but PEPFAR [US President's Emergency Plan for AIDS Relief] has also helped [with] a contribution of 900 million rand [US$120 million] over a two-year period. We are also hoping to apply to other multilateral organizations, like the Global Fund [to Fight AIDS, Tuberculosis and Malaria], which has been funding a lot of our HIV/AIDS campaign. In the past [we] ... never applied for ARV [funding] ... The Global Fund never funded us for ARVs because ... there was no internal willingness to do so [on the part of government] ... in the next [Global Fund] round [of grants] we will definitely apply for funding for ARVs.

In a nation ravaged by AIDS, a disease still hidden in shadows of stigma and shame, President Jacob Zuma of South Africa has begun to engage in an extraordinarily open conversation about sex, AIDS and H.I.V. prevention, one ignited in part by his own recent admission that he had unprotected sex during an extramarital affair.

Last month, as he announced a vast expansion of H.I.V. testing and AIDS services, he publicly took an H.I.V. test and disclosed that he had tested negative for the virus. Then in a frank interview on Thursday, Mr. Zuma said that he had been circumcised and had encouraged his sons to undergo the procedure, which can reduce a man's risk of contracting H.I.V. by more than half.

As an influential leader and a Zulu, South Africa's largest ethnic group and one that had abandoned circumcision in the 19th century, Mr. Zuma could encourage other men to be circumcised through his personal endorsement of the procedure, scientists and public health officials say.

Despite being the center of the epidemic -- with 5.7 million H.I.V.-positive people, more than any other country -- South Africa had lagged behind some other African nations in promoting circumcision and making it available to the public, steps that experts say could help reduce the spread of new infections in the long run.

South Africa now plans to circumcise millions of men in the coming years and started its drive last month in the Zulu heartland, where infection rates are highest. The burden of the disease has strained the public health system here and led to falling life expectancies and ballooning costs for treatment, prompting health officials to act more aggressively to reduce the pace of new H.I.V. infections.

The global war on AIDS has racked up enormous successes over the past decade, most notably by providing drugs for millions of infected people in developing countries who would be doomed without this life-prolonging treatment. Now the campaign is faltering.

Donations from the United States and other wealthy countries have leveled off while the number of people infected with H.I.V., the AIDS virus, grows by a million a year. By one informed estimate, only $14 billion will be available of some $27 billion needed this year to fight the disease in the developing world. Fewer than 4 million of the 14 million people who need immediate drug treatment are receiving it - far short of the goal of universal access set by the United States and others.

Donor nations cite the economic crisis and tight budgets as reasons to slow their contributions to the global fight against AIDS. The Obama administration and many donor nations apparently believe that more lives could be saved by fighting other cheaper diseases, such as respiratory illnesses, diarrhea, malaria and measles.

The results of those decisions can be seen in Uganda and other countries where, as Donald G. McNeil Jr. recently reported in The Times, the campaign against AIDS seems to be falling apart. Although the number of Ugandans receiving drug treatments jumped from fewer than 10,000 a decade ago to nearly 200,000 today, hundreds of thousands more Ugandans need the drugs and likely can't get them because clinics now routinely turn new patients away.

Editor's Note: This article is an editorial in response to Donald McNeil's articles published on 10 May in the New York Times, "At Front Lines, Global War on AIDS Is Falling Apart". Read additional letters to the editor about McNeil's articles here.

The global response to AIDS is in trouble. There are yawning gaps in funding for proven prevention and treatment and a crisis in political will for continued support of AIDS programs. Those of us working on the AIDS epidemic face skepticism about whether disease-specific funding for AIDS is cost effective. Those of us working on AIDS vaccines face skepticism about whether limited funds for AIDS should include funding for AIDS prevention research. This May 18th -- HIV Vaccine Awareness Day -- we have to meet this skepticism with honesty about what we know and clarity about the cause for hope that exists today in a way that it never has before.

This year, for the first time, we mark the Day with hope based on evidence from a trial in humans that shows that an AIDS vaccine is possible. This hope flows from the announcement, in September last year, of a modest level of protection among participants in the Thai Prime-Boost trial who received the vaccine. The results were complex, in part, because the difference in numbers of HIV infections in vaccine and placebo recipients in the trial is small. AVAC and others have spent the past eight months working to explain the uncertainty within these results and the need for follow-up research.

We will keep on explaining the complexities, but it is potentially disastrous if all that advocates, potential donors and future HIV vaccine trial volunteers and researchers think about the trial is that it gave a murky result, that it "failed" (to quote a recent New York Times article) or that it left us no closer to an AIDS vaccine than we had been before. So on this HIV Vaccine Awareness Day, our most important message is that the Thai Prime-Boost trial changed the game for AIDS vaccines. It offered evidence that scientists have been chasing for more than twenty years. The result itself was surprising, so, perhaps, it is no surprise that it prompted skepticism from some researchers, advocates and reporters.

Although major inroads into making antiretroviral therapy available in resource-poor countries have been made, there is an urgent need for an effective vaccine administered shortly after birth, which would protect infants from acquiring human immunodeficiency virus type 1 (HIV-1) through breastfeeding. Bacillus Calmette-Guerin (BCG) is given to most infants at birth and its recombinant form could be used to prime HIV-1-specific responses for a later boost by heterologous vectors delivering the same HIV-1-derived immunogen. Here, two groups of neonate Indian rhesus macaques were immunized with either novel candidate vaccine BCG.HIVA⁴⁰¹ or its parental strain AERAS-401 followed by two doses of recombinant modified vaccinia virus Ankara MVA.HIVA. The HIVA immunogen is derived from African clade A HIV-1. All vaccines were safe, giving local reactions consistent with the expected response at the injection site. No systemic adverse events or gross abnormality was seen at necropsy. Both AERAS-401 and BCG.HIVA⁴⁰¹ induced high frequencies of BCG-specific IFN-gamma-secreting lymphocytes that declined over 23 weeks, but the latter failed to induce detectable HIV-1-specific IFN-gamma responses. MVA.HIVA elicited HIV-1-specific IFN-gamma responses in all 8 animals, but, except for one animal, these responses were weak. The HIV-1-specific responses induced in infants were lower compared to historic data generated by the two HIVA vaccines in adult animals, but similar to other recombinant poxviruses tested in this model. This is the first time these vaccines were tested in newborn monkeys. These results inform further infant vaccine development and provide comparative data for two human infant vaccine trials of MVA.HIVA.

For many diseases vaccines are lacking or only partly effective. Research on protective immunity and adjuvants that generate vigorous immune responses may help generate effective vaccines against such pathogens.

Review
The immune system is functionally diverse, able to make a refined response to hundreds of different types of infectious organisms. The initiation of an immune response to an infection requires collaboration between innate immune cells, which recognize general distinguishing features of pathogens, and the T lymphocytes of the adaptive immune system, whose highly variable antigen receptors are specific for a given pathogen. The activation of T lymphocytes depends on interactions with professional antigen-presenting cells (APCs), specialized cells of the innate immune system that are directly activated by the pathogens they engulf and regurgitate for presentation to, and activation of, T cells. The T cells then proliferate and are mobilized to protect the body by activating other immune cells or by killing infected cells. Among the immune cells activated by T lymphocytes, most importantly, are the B lymphocytes that produce antibodies. T lymphocytes direct the types of antibodies that B cells produce and the activity of other immune cells, thereby directing the immune response to optimally provide protection against different types of infections. At the end of an immune response, the majority of activated B and T cells will undergo apoptosis, but a small number remain as memory cells, primed ready in case the host is exposed to the same infection [1,2]. Vaccines must work in a similar way, priming antigen-specific T and B cells, some of which convert to the memory cells that will control subsequent infections by the invader targeted by the vaccine. Moreover, like the infection itself, the vaccine must generate the optimal type of immune response to protect against a particular pathogen.

Induction of type I interferons (IFN) is a central feature of innate immune responses to microbial pathogens and is mediated via Toll-like receptor (TLR)-dependent and -independent pathways. Prothymosin-a [alpha] (ProTa), a small acidic protein produced and released by CD8+ T cells, inhibits HIV-1, although the mechanism for its antiviral activity was not known. We demonstrate that exogenous ProTa acts as a ligand for TLR4 and stimulates type I IFN production to potently suppress HIV-1 after entry into cells. These activities are induced by native and recombinant ProTa, retained by an acidic peptide derived from ProTa, and lost in the absence of TLR4. Furthermore, we demonstrate that ProTa accounts for some of the soluble postintegration HIV-1 inhibitory activity long ascribed to CD8+ cells. Thus, a protein produced by CD8+ T cells of the adaptive immune system can exert potent viral suppressive activity through an innate immune response. Understanding the mechanism of IFN induction by ProTa may provide therapeutic leads for IFN-sensitive viruses.

The development of effective microbicides for the prevention of HIV-1 sexual transmission represents a primary goal for the control of the AIDS epidemics worldwide. A promising strategy is the use of bacteria belonging to the vaginal microbiota as live microbicides for the topical production of HIV-1 inhibitors. We have engineered a human vaginal isolate of Lactobacillus jensenii to secrete the anti-HIV-1 chemokine RANTES as well as C1C5 RANTES, a mutated analogue that acts as a CCR5 antagonist and therefore is devoid of pro-inflammatory activity. Full-length wild type and C1C5 RANTES secreted by L. jensenii were purified to homogeneity and shown to adopt a correctly folded conformation. Both RANTES variants were shown to inhibit HIV-1 infection in CD4+ T cells and macrophages, displaying strong activity against HIV-1 isolates of different genetic subtype. This work provides proof of principle for the use of L. jensenii-produced C1C5 RANTES to block HIV-1 infection of CD4+ T cells and macrophages, setting the basis for the development of a live anti-HIV-1 microbicide targeting CCR5 in an antagonistic manner.

Mycobacterium bovis bacillus Calmette-Guerin (BCG), which elicits a degree of protective immunity against tuberculosis, is the most widely used vaccine in the world. Due to its persistence and immunogenicity, BCG has been proposed as a vector for vaccines against other infections, including HIV-1. BCG has a very good safety record, although it can cause disseminated disease in immunocompromised individuals. Here, we constructed a recombinant BCG vector expressing HIV-1 clade A-derived immunogen HIVA using the recently described safer and more immunogenic BCG strain AERAS-401 as the parental mycobacterium. Using routine ex vivo T-cell assays, BCG.HIVA401 as a stand-alone vaccine induced undetectable and weak CD8 T-cell responses in BALB/c mice and rhesus macaques, respectively. However, when BCG.HIVA401 was used as a priming component in heterologous vaccination regimens together with recombinant modified vaccinia virus Ankara-vectored MVA.HIVA and ovine atadenovirus-vectored OAdV.HIVA vaccines, robust HIV-1-specific T-cell responses were elicited. These high-frequency T-cell responses were broadly directed and capable of proliferation in response to recall antigen. Furthermore, multiple antigen-specific T-cell clonotypes were efficiently recruited into the memory pool. These desirable features are thought to be associated with good control of HIV-1 infection. In addition, strong and persistent T-cell responses specific for the BCG-derived purified protein derivative (PPD) antigen were induced. This work is the first demonstration of immunogenicity for two novel vaccine vectors and the corresponding candidate HIV-1 vaccines BCG.HIVA401 and OAdV.HIVA in nonhuman primates. These results strongly support their further exploration.

Background At present, the relatively sudden appearance and explosive spread of HIV throughout Africa and around the world beginning in the 1950s have never been adequately explained. Theorizing that this phenomenon may be somehow related to the eradication of smallpox followed by the cessation of vaccinia immunization, we undertook a comparison of HIV-1 susceptibility in the peripheral blood mononuclear cells from subjects immunized with the vaccinia virus to those from vaccinia naive donors. Results Vaccinia immunization in the preceding 3-6 months resulted in an up to 5-fold reduction in CCR5-tropic but not in CXCR4-tropic HIV-1 replication in the cells from vaccinated subjects. The addition of autologous serum to the cell cultures resulted in enhanced R5 HIV-1 replication in the cells from unvaccinated, but not vaccinated subjects. There were no significant differences in the concentrations of MIP-1alpha, MIP-1beta and RANTES between the cell cultures derived from vaccinated and unvaccinated subjects when measured in culture medium on days 2 and 5 following R5 HIV-1 challenge. Discussion Since primary HIV-1 infections are caused almost exclusively by the CCR5-tropic HIV-1 strains, our results suggest that prior immunization with vaccinia virus might provide an individual with some degree of protection to subsequent HIV infection and/or progression. The duration of such protection remains to be determined. A differential elaboration of MIP-1alpha, MIP-1beta and RANTES between vaccinated and unvaccinated subjects, following infection, does not appear to be a mechanism in the noted protection.

Click here to read coverage of this study in BBC News.

Elucidating virus-host interactions responsible for HIV-1 transmission is important for advancing HIV-1 prevention strategies. To this end, single genome amplification (SGA) and sequencing of HIV-1 within the context of a model of random virus evolution has made possible for the first time an unambiguous identification of transmitted/founder viruses and a precise estimation of their numbers. Here, we applied this approach to HIV-1 env analyses in a cohort of acutely infected men who have sex with men (MSM) and found that a high proportion (10 of 28; 36%) had been productively infected by more than one virus. In subjects with multivariant transmission, the minimum number of transmitted viruses ranged from 2 to 10 with viral recombination leading to rapid and extensive genetic shuffling among virus lineages. A combined analysis of these results, together with recently published findings based on identical SGA methods in largely heterosexual (HSX) cohorts, revealed a significantly higher frequency of multivariant transmission in MSM than in HSX [19 of 50 subjects (38%) versus 34 of 175 subjects (19%); Fisher's exact p = 0.008]. To further evaluate the SGA strategy for identifying transmitted/founder viruses, we analyzed 239 overlapping 5' and 3' half genome or env-only sequences from plasma viral RNA (vRNA) and blood mononuclear cell DNA in an MSM subject who had a particularly well-documented virus exposure history 3-6 days before symptom onset and 14-17 days before peak plasma viremia (47,600,000 vRNA molecules/ml). All 239 sequences coalesced to a single transmitted/founder virus genome in a time frame consistent with the clinical history, and a molecular clone of this genome encoded replication competent virus in accord with model predictions. Higher multiplicity of HIV-1 infection in MSM compared with HSX is consistent with the demonstrably higher epidemiological risk of virus acquisition in MSM and could indicate a greater challenge for HIV-1 vaccines than previously recognized.

The importance of male spousal involvement in the prevention of mother-to-child transmission (pMTCT) programs is incremental to maintain family health and adherence to human immunodeficiency virus (HIV) treatment and prevention regimens. This study examined reasons for men's involvement in pMTCT initiatives sought by their wives and other HIV-related services in western Kenya. Data were collected from 146 men and women during 16 focus groups across four different HIV-related clinics. Four different groups of participants were recruited: (1) male spouses of women enrolled in pMTCT within the past 12 months; (2) married men who were participating in support groups of the AMPATH Support Network; (3) married women living with HIV who were currently enrolled in pMTCT; and (4) married women who were HIV negative and currently enrolled in pMTCT. Demographic information was collected from each participant using a written questionnaire. Focus groups were conducted to determine the factors associated with men's participation in pMTCT services. From the emergent themes revealed by the focus groups, several intervention strategies were identified to increase male involvement in HIV-related services, specifically pMTCT. They include: couple's counseling, weekend clinic hours or extended weekday hours, community education regarding HIV-related services offered at clinics, and making clinics more male-oriented. These findings provide a starting point for the development of interventions to increase men's involvement in pMTCT programs.

This paper examines the relationship between bridewealth, socio-demographics, and sexual and reproductive practices among a group of women in Harare, Zimbabwe. The study sample was recruited as part of a six-month safety trial of the diaphragm and a microbicide, between August 2004 and April 2005 in Harare, Zimbabwe. Women underwent two screening visits: first, women completed a demographic and behavioral interviewer-administered questionnaire which included questions on bridewealth; at the second visit, women were offered HIV testing and counseling. Our results included: 417 women were married (currently or in the past) and almost half had had bridewealth negotiated as part of the marriage process. In multivariate analyses, women who were married with bridewealth had more years of education (OR 1.17, 95%CI 1.03-1.32), a higher age of coital debut (OR 1.37, 95%CI 1.09-1.71), and increased likelihood of having ever used male condoms (OR 1.54, 95%CI 1.01-2.37) compared with women who had been married without bridewealth. Bridewealth may be a relevant area of traditional culture to further examine in relation to HIV risk, for its potential association with co-factors that can reduce risk of HIV infection among women in Southern Africa.

Background: Women have been regularly underestimated in their ability to care for and wear cervical barrier devices such as diaphragms appropriately. Methods: Data from two non-randomised, non-blinded, non-significant risk acceptability studies of a novel cervical barrier device, the SILCS diaphragm, conducted in the Dominican Republic (n = 20), South Africa (n = 21) and Thailand (n = 20), are used to provide insights into the fundamental question of how women actually use an intravaginal device within the constraints of low-resource settings. In all sites, couples not at risk of pregnancy and at low risk of sexually transmissible infections used the SILCS diaphragm four times and provided feedback on acceptability, care and use of the device via product use questionnaires and gender-specific debriefing interviews. Results: Data from user acceptability studies in these three countries provide an intimate view of how women care for and store the SILCS diaphragm, and both female and male perceptions about handling and re-using it. Results support the view that women are able to wear and care for diaphragms successfully in a variety of settings. In general, male partners were also supportive of care and reuse of the diaphragm. Conclusions: While the results from these studies indicate that women are able to find ways to cope successfully with the logistics of wearing and caring for an intravaginal device, further supportive evidence from a woman-centred perspective is crucial for reproductive health policymakers and program managers. The authors contend that it is time to reassess perceived constraints to barrier protection.

See editorial on this article:
Holmes W. Adding to the menu of modern methods - the diaphragm. Sexual Health 7(2):193-198.

Background: The importance of the acceptability of rectal microbicides for HIV and sexually transmissible infections (STIs) prevention is widely recognised. Given relatively consistent use of lubricants for anal intercourse (AI) and the potential for lubricant-like rectal microbicides, understanding barriers to lubricant use may help inform hurdles likely to be encountered once a rectal microbicide becomes available. Methods: We conducted an internet-based survey using a 25-item questionnaire to assess AI and lubricant use, including lubricant preferences and barriers to use. Results: The majority of the 6124 respondents who reported AI were male (93%), 25 years or older (80%) and from North America (70%). Consistent condom use during AI was reported by a minority (35%) and consistent lubricant use was reported by over half of respondents. Reasons for non-use differed by age and region. Among men, those <25 years were more likely to report barriers around cost compared with those 45 and older (odds ratio (OR) = 6.64; 95% confidence interval (CI) 3.14-14.03). European men (OR = 1.92; 95% CI 1.50-2.45), Latin American women (OR = 3.69; 95% CI 1.27-10.75) and Asian women (OR = 4.04; 95% CI 1.39-11.78) were more likely to report sexual preference as a reason for non-use. Conclusions: Rectal lubricants are widely used, but barriers to use vary by age and region for dry sex. A lubricant-like rectal microbicide would potentially be acceptable and such a product may be useful as a method of HIV prevention. However, targeted marketing and educational approaches may be needed to enhance use and acceptability of such a product.

Objectives The aim of the study was to assess whether subpopulations with sufficiently high HIV incidences for HIV prevention trials can be identified in low HIV incidence settings such as Australia. Methods In a community-based cohort study of HIV-negative homosexually active men in Sydney, Australia, potential risk factors associated with an annual HIV incidence of >=2 per 100 person-years (PY) were identified. A stepwise procedure ranked these factors according to HIV incidence, to create a 'high-incidence' subgroup of participants. Willingness to participate in HIV prevention trials was assessed. Results Although the incidence in the cohort overall was only 0.78 per 100 PY, nine risk variables were associated with an HIV incidence of 2 per 100 PY or greater. Stepwise inclusion of these variables revealed a 'high-incidence' subgroup of men representing 24% of the total follow-up time with a combined HIV incidence of 2.71 per 100 PY, who reported at least one of three risk factors in the past 6 months. These men were more willing than others to participate in vaccine and antiretroviral therapy HIV prevention trials. Conclusions These findings demonstrate that it is possible to identify high HIV incidence subpopulations in low-incidence settings such as Australia, and these men are of above average willingness to participate in HIV prevention trials.

Single genome amplification (SGA) and sequencing of HIV-1 RNA in plasma of acutely infected humans allows the identification and enumeration of transmitted/founder viruses responsible for productive systemic infection. Use of this strategy as a means for identifying transmitted viruses suggested that intra-rectal SIV inoculation of macaques recapitulates key features of human rectal infection. However, no studies have used the SGA strategy to identify vaginally transmitted virus(es) in macaques or to determine how early SIV diversification in vaginally infected animals compares with HIV-1 in humans. We used SGA to amplify 227 partial env sequences from a SIVmac251 challenge stock and from 7 rhesus macaques at the earliest plasma viral RNA positive time point after low and high dose intravaginal inoculation. Sequences were analyzed phylogenetically to determine the relationship of transmitted/founder viruses within and between each animal and the challenge stock. In each animal, discrete low-diversity env sequence lineages were evident and these coalesced phylogenetically to identical or near-identical env sequences in the challenge stock, thus confirming the validity of the SGA sequencing and modeling strategy for identifying vaginally transmitted SIV. Between 1 and 10 viruses were responsible for systemic infection, similar to humans infected by sexual contact and the set of viruses transmitted to the 7 animals studied represented the full genetic constellation of the challenge stock. These findings recapitulate many of the features of sexual HIV-1 transmission in women. Further the SIV rhesus macaque model can be used to understand the factors that influence the transmission of single versus multiple SIV variants.

We investigated HIV-1-vaccine-induced lymphoproliferative responses in healthy volunteers immunized intradermally or intramuscularly (with or without adjuvant GM-CSF protein) with DNA expressing HIV-1 gag, env, rev and rt at months 0, 1 and 3 using a Biojector and boosted at nine months with MVA expressing heterologous HIV-1 gag, env and pol. Lymphoproliferative responses to AT-2 inactivated HIV-1 antigen were tested by a 3H-thymidine uptake assay and a Flow-cytometric Assay of Specific Cell-mediated Immune-response in Activated whole blood (FASCIA-WB) two weeks after the HIV-MVA boost (n=38). A FASCIA using peripheral blood mononuclear cells (FASCIA-PBMC) was also employed (n=14). Thirty-five of 38 (92%) vaccinees were reactive by the 3H-thymidine uptake assay. Thirty-two of 38 (84%) vaccinees were reactive by the CD4+ T cell FASCIA-WB and seven of 38 (18%) also exhibited CD8+ T cell responses. There was strong correlation between the proliferative responses measured by the 3H-thymidine uptake assay and CD4+ T cell FASCIA-WB (r=0.68; p<0.01). Fourteen vaccinees were analyzed using all three assays. Ten of 14 (71%) and 11/14 (79%) demonstrated CD4+ T cell responses in FASCIA-WB and FASCIA-PBMC, respectively. CD8+ T cell reactivity was observed in 3/14 (21%) and 7/14 (50%) using the FASCIA-WB and FASCIA-PBMC, respectively. All fourteen were reactive using the 3H-thymidine uptake assay. The overall HIV-specific T cell proliferative response in the vaccinees employing any of the assays was 100% (38/38). A standardized FASCIA-PBMC, which allows simultaneous phenotyping may be an option to the 3H-thymidine uptake assay for assessment of vaccine-induced T cell proliferation, especially in isotope-restricted settings.

Background Guidelines for initiating ART recommend pregnancy testing, typically a urine test, as part of the basic laboratory package. The principal reason for this recommendation is that Efavirenz, a first-line antiretroviral medication, has the potential of causing birth defects when used in the first trimester of pregnancy and is therefore contraindicated for use by pregnant women. Unfortunately, in many African countries pregnancy tests are not routinely provided or available in ART clinics, and, when available outside clinics, are often not affordable for clients. Recently, the World Health Organization added a family planning job aid called the 'pregnancy checklist,' developed by researchers at Family Health International, as a recommended tool for screening new ART clients to exclude pregnancy. Although the checklist has been validated for excluding pregnancy among family planning clients, there are no data on its efficacy among ART clients. This study was conducted to assess the clinical performance of a job aid to exclude pregnancy among HIV positive women initiating ART. Methods Non-menstruating women eligible for ART were enrolled from 20 sites in four provinces in Zambia. The pregnancy checklist was administered followed by a urine pregnancy test as a reference standard. Sensitivity, specificity, and positive and negative predictive values were estimated. Results Of the 200 women for whom the checklist ruled out pregnancy, 198 were not pregnant, for an estimated negative predictive value of 99%. The sensitivity of the checklist was 90.0%, and specificity was 38.7%. Among the women, 416 out of 534 (77.9%) did not abstain from sex since their last menses. Only 72 out of the 534 women (13.4%) reported using reliable contraception. Among the 416 women who did not abstain, 376 (90.4%) did not use reliable contraception. Conclusion The pregnancy checklist is effective for excluding pregnancy in many women initiating ART, but its moderate sensitivity and specificity precludes its use to completely replace pregnancy testing. Its use should be encouraged in low resource settings where pregnancy tests are unavailable or must be rationed. Family planning methods should be available and integrated into ART clinics.

International Rectal Microbicide Advocates (IRMA) will officially release its third landmark report -- "From Promise to Product: Advancing Rectal Microbicide Research and Advocacy" -- at the 2010 International Microbicides Conference in Pittsburgh, PA taking place May 22-25, 2010. The ambitious, comprehensive document reports on the growing scientific activity in the rectal microbicide field, capturing the optimism among researchers and advocates alike as the field sets its sights on the development of safe and effective rectal-specific products that will provide protection against HIV during anal intercourse.

Additionally, IRMA continues to call for a Global Rectal Microbicide Development plan by which stakeholders can coordinate efforts across the full range of scientific activities, developing strategies and setting priorities. Such a plan does not yet exist. Dr. Ian McGowan, Scientific Vice-Chair on the IRMA Steering Committee and co-Principal Investigator of the Microbicide Trials Network says, "A detailed map such as a Global Rectal Microbicide Development Plan is absolutely necessary if we are going to make the best use of each and every research dollar in this time of global recession and constricted resources."

An updated resource tracking of funds specifically allocated to rectal microbicide research and development -- the only such exercise -- is followed by a call for escalating funding over the next 10 years and for increased diversity in the funding portfolio as well. The United States National Institutes of Health currently provides over 90% of global resources devoted to rectal microbicide activities, and nations of the European Union and global philanthropic organizations need to support this critical work as well.

The full report is available as a PDF online in English and in Spanish.

Fund Title: Act Against AIDS Leadership Initiative (AAALI)

Grant Amounts: Approximate Current Fiscal Year Funding: $ 2,640,000, based on availability of funds; Approximate Total Project Period Funding: $15,000,000, based on 5 years, at $3,000,000 per year. (This amount is an estimate, and is subject to availability of funds and includes direct and indirect costs.)

Description: The purpose of the AAALI is to (1) incorporate HIV/AIDS education and awareness, prevention, and communication strategies into the day-to-day activities of AAALI organizations, (2) to integrate HIV prevention in communication, mobilization, and outreach activities of national organizations that have proven reach and credibility within African American, Hispanic/Latino, or MSM communities, and that have not had a historically, primary HIV/AIDS focus, and (3) to create a network of these organizations that can support the shared implementation of innovative, credible, and effective approaches that respond to the unique challenges facing HIV prevention efforts among African Americans, Hispanic/Latinos, or MSM. The AAALI is designed to harness the collective strength and reach of traditional, longstanding institutions to increase HIV-related awareness, knowledge, and action within African American, Hispanic/Latino, or MSM communities.

Sponsor(s): US Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention

Application Due Date: 06/14/2010

For more than a decade, researchers and advocates have marked HIV Vaccine Awareness Day with varying degrees of hope, cynicism and despair. This year, in large part because of the results of the Thai Prime-Boost vaccine study, there is greater cause for hope than ever before and a renewed sense of urgency to transform this hope into a reality.

In September 2009, the world's largest AIDS vaccine trial to date showed the first evidence that an experimental AIDS vaccine could lower the risk of HIV infection. The results were complex; the observed benefit from the vaccine was modest; and the field is still years away from a highly protective vaccine.

"The caveats to the Thai Prime-Boost study results are important and true. But letting them become the entire story does a severe, even dangerous, disservice to the field, the trial and especially the 16,000 people who participated in the trial," said Mitchell Warren, Executive Director of AVAC: Global Advocacy for HIV Prevention. "Despite the many perspectives on and interpretations of the trial -- and its results -- the Thai AIDS vaccine trial provides evidence for the first time that it is possible to reduce the risk of HIV infection with a vaccine. AVAC and others have worked to explain the uncertainty of the results and the need for follow-up research. We will continue to do this because the science is complicated, and the future is unknown."

But for HIV Vaccine Awareness Day, AVAC's loud and clear message is that the Thai Prime-Boost trial changed the game for AIDS vaccines. A preventive AIDS vaccine is possible. The results were surprising to many and prompted some skepticism. But it is potentially disastrous if all that advocates, potential donors and future HIV vaccine trial volunteers and researchers think about the trial is that it gave a murky result, that it failed or that it left us no closer to an AIDS vaccine than we had been before.

Read Executive Director Mitchell Warren's piece, Ending AIDS: Grounds for Despair, Cynicism or Hope? in the Huffington Post.

Placing the search for a cure for HIV/AIDS firmly at the center of its research efforts, amfAR, The Foundation for AIDS Research, on Tuesday announced the first round of grants to a consortium of leading researchers to develop strategies for eradicating HIV infection. The initial round of funding for the newly constituted amfAR Research Consortium on HIV Eradication (ARCHE) includes projects in areas that are widely considered central to HIV eradication.