2 JULY 2010, VOLUME 11, ISSUE 23

The White House is poised to release the country's first comprehensive domestic strategy against AIDS, as funds to prevent infections have failed to halt the epidemic in those most at risk of the disease, AIDS groups said. Release of the National AIDS Strategy may come as early as today, fulfilling Obama's campaign pledge to unify priorities among federal agencies and state partners, said Mitchell Warren, executive director of the New York-based AIDS Vaccine Advocacy Coalition, a nonprofit advocacy group.

HIV is contracted by about 56,000 Americans each year, and the mounting tally of people living with the disease shows no sign of stopping, according to the U.S. Centers for Disease Control and Prevention. While the U.S. attack on AIDS overseas has been led by the President's Emergency Plan for AIDS Relief, or PEPFAR, domestic efforts are a patchwork of programs with little oversight, said Chris Collins, director of Public Policy at the American Foundation for AIDS Research, or amfAR.

"Our response to the global epidemic is squarely focused on outcomes, and we need to get to that point in our domestic responses," Collins said. "In the United States we have a concentrated epidemic among a few populations but we don't have a response that fits our epidemic." Obama's new AIDS strategy needs to focus more on gay men and blacks, among whom new HIV infection rates outweigh other groups, Collins said.

The world's eight richest nations or G-8 is contributing $7.3 billion to improve maternal health and reduce infant mortality globally, according to Canadian Prime Minister Stephen Harper. The aid package was announced Friday at the lakeside resort town in the Muskoka region, where leaders of the G-8 are holding a summit.

The United States, Japan and major European powers will contribute $5 billion and the remainder will come from less-developed nations and the Bill and Melinda Gates Foundation. Canada, which is hosting the summit, is committing $1.1 billion to the aid package in the next five years. The aid package aims to address the estimated 500,000 women who dies during pregnancy and childbirth as well as the death of nearly 9 million children under 5 years old, especially in Africa.

The Global Fund and the UNAIDS have assured Government that they would continue to fund the Ministry of Health, dispelling reports that they had suspended support. And Health Minister Kapembwa Simbao has assured donors that Government has undertaken measures to address the fraud and corruption at the Ministry of Health. Global Fund and UNAIDS executive directors Michael Kazatchkine and Michel Sidibe respectively assured Mr Simbao, who was leading a delegation to Geneva, Switzerland yesterday of their organisations continued support to Zambia. This follows reports that donors had suspended funding to the Ministry of Health. The minister, who was leading a delegation to Geneva held meetings with the two organisations over the last two days. He explained that Government had identified and was now prosecuting the alleged perpetrators of fraud at the ministry. The ministry has also changed the principal recipientship from the ministry to the United Nations Development Programme (UNDP) as an interim measure while it was still being restructured.

Zambia President Rupiah Banda on Saturday accused donors of blackmail after the Global Fund suspended health assistance and the European Union halted aid for road construction citing corruption in the country. "We must not allow donors to feel they can interfere in the internal affairs of this country because it is a sovereign and independent state," Banda said on state-owned radio ZNBC. "We did not ask anyone to fund the road sector or the health sector, so they must not use that as blackmail."

The health aid freeze, the latest graft scandal to hit Banda before an election due next year, is likely to affect the southern African country's fight against AIDS, tuberculosis and malaria. Health Minister Kapembwa Simbao played down fears of a looming health crisis saying the Global Fund would still continue supporting Zambia but the funding would now be made available through the United Nations Development Programme (UNDP). Lee Habasonda, the executive director of the Southern African Centre for the Constructive Resolution of Disputes said Banda's statement could harm Zambia's relations with the donors.

The US government has committed US$88 million to strengthen Zambia's health care system through a five-year programme that entails capacity building in the sector. Charge d' affaires at the US embassy Michael Koplovsky said in a statement that by working with his government, Zambia could reduce the need for outside development assistance and create a Zambian-driven future. The contract to implement the programme had been awarded to Abt Associates and it would work with the Ministry of Health, focusing on HIV/AIDS, reproductive health, malaria and child health among others. The Zambia Integrated Systems Strengthening Programme (ZISSP) would be supported by the US Agency for International Development (USAID) to build on past US funded programmes. Through the ZISSP, the American people would provide training to doctors, clinical officers and nurses to enable them deliver higher quality medical care.

In mid-July, AIDS experts from around the world will gather for the 18th international AIDS conference. The focus will be on where AIDS is being defeated and where it is re-emerging. Unfortunately, Uganda will be discussed in the second category. At the start of the AIDS epidemic, countries around the world turned to Uganda and saw a nation that forcefully addressed AIDS, using straight talk, evidence-based approaches, and the engagement of people living with HIV. Ugandan government and civil society leaders became famous on the world stage.

So much has changed. Intolerance and bias have replaced effective approaches. Widespread corruption, including the theft of millions of dollars targeted for HIV services, has damaged Uganda's anti-AIDS efforts, as well as its reputation. Discriminatory, punitive laws and policies are proposed instead of common-sense approaches. There is no longer the sense that "AIDS affects us all."

The HIV and AIDS Prevention and Control Bill tabled in Parliament recently is a case in point. If passed in its current form, the bill would criminalise a broad range of conduct, including intentional and attempted HIV transmission and "misleading statements or information regarding curing, preventing, or controlling HIV."

Policies that criminalise drug use are increasing the spread of AIDS, experts said Monday, calling for a milder and more effective approach to preventing drug use. "Misguided drug policies... fuel the AIDS epidemic and result in violence, increased crime rates and destabilisation of entire states," said Julio Montaner, president of the International AIDS Society. "Yet there is no evidence they have reduced rates of drug use or drug supply," he added in a statement.

Montaner and other AIDS experts, including Francoise Barre-Sinoussi, the co-discoverer of the HIV virus, published Monday a Vienna Declaration calling for an end to ineffective and costly drug policies and for more emphasis on strategies that have been scientifically proven to work. In some parts of the world, such as eastern Europe and central Asia, injecting drugs is the main cause for the spread of HIV, the experts said. More widespread needle and syringe programmes, as well as access to opioid substitution therapy (OST), by which illegal drugs are substituted for less harmful substances, would lower the number of HIV infections without increasing drug use, they added.

A deal to broaden Gilead's research expertise into protein kinase biology has been finalised with the $120m acquisition of CGI Pharmaceuticals, in a deal that compliments its comprehensive selection of anti-HIV treatments. The acquisition signals Gilead's intentions to move into small molecule drug discovery, an area in which small molecule therapeutics is expected to gain most progress in inflammation and cancer therapies. Small molecule drugs currently dominate central nervous system and infectious disease treatments and biotech firms such as Genentech currently have a pipeline that emphasises therapeutics in the oncology and immunology areas. The agreement comes as a selection of drug producers have been making licensing deals with drug developers in an attempt to shore up their pipelines.

The pharmaceutical industry's funding of research and its success rates in developing new medicines both fell last year, raising concerns about the future of the sector, according to data to be released on Monday. While the number of innovative medicines launched in 2009 was up slightly on the previous two years, investment across drugmaking companies in research and development fell while failure rates increased.

As pharmaceutical companies have cut back in recent months on research and development activities in the search for savings, aggregate spending on developing new drugs fell by 0.3 per cent. Cumulative investment as a proportion of sales fell to 15 per cent across the sector. Sales from products launched within the past five years accounted for just 7 per cent of total drug sales -- and as low as 2.3 per cent among the large companies -- highlighting their extreme reliance on older products that are soon to lose exclusivity and see prices drop as patents expire.

Failure rates of experimental drugs have also continued to rise, with the number of products abandoned in late-stage Phase 3 trials in the industry doubling to almost 40 in 2007-09 compared with 2004-06. CMR estimated that for every 12 drugs entering pre-clinical research, only two make it to Phase 3 and just one is submitted to regulators for approval as safe and effective in patients.

The United Nations Development Programme (UNDP), backed by UNAIDS (the joint UN programme on HIV and AIDS), has launched an expert body to examine discriminatory laws, regulations, and social norms that hinder national responses and impede access to treatment for people with HIV, in particular those from vulnerable groups.

"In many places social and legal challenges to human rights are undermining efforts at achieving universal access to HIV/AIDS prevention, care, and support," said the UNDP's administrator, Helen Clark, at the launch of the Global Commission on HIV and the Law in Geneva on 24 June.

Members of the commission include a former president of Brazil, Fernando Cardoso; the director of the advocacy group AIDS Free World, Stephen Lewis; the US Congresswoman Barbara Lee; Miriam Were, a public health advocate from Kenya; and Justice Edwin Cameron of South Africa.

Results from the 2004/5 Ugandan Behavioural Sero Survey, the latest and most robust country-wide population level HIV prevalence study indicated an adult prevalence of 6.4 per cent, a figure far lower that the over 15 per cent prevalence registered in 1991/92. This drastic improvement was a result of visionary leadership and efforts towards prevention and treatment. With improvements in HIV/Aids treatment and support systems, people living with HIV do not only live longer but also enjoy better quality of life.

Today, only 54 per cent of the 350,000 people requiring ARVs are on these much needed drugs. Over the years, increased attention to HIV/Aids treatment overshadowed prevention efforts leading to increased numbers of new infections country wide. The strategy of Abstinence, Faithfulness and Condom use worked well in the early days of the epidemic but now seem inadequate to curtail new infections.

The Big read: "Nowhere to be seen" is how one could describe the attention given to children only a few years ago - two decades into the HIV/Aids epidemic. Tear-stained faces and sick parents illustrated how fundraising efforts seldom benefited children affected by the disease. Many important HIV/Aids gatherings used children "decoratively", having them dance and wave flags at opening and closing ceremonies, but did little to address the enormous HIV/Aids-related challenges to children's health and wellbeing.

All this has since changed. Concerted efforts by collaborating groups have pushed forward the "child agenda". The first plenary address in more than 20 years of the International Aids Conference was delivered in Mexico City in 2008, calling attention to the neglect of children and the importance of supporting families. Today, prevention of infection among newborns is a key goal of the US President's Emergency Plan for Aids Relief and 10% of its funds are earmarked for children affected by Aids.

In May this year, the Global Fund to Fight Aids, Tuberculosis and Malaria launched the Born HIV-Free Campaign. Supported by France's first lady and Global Fund ambassador, Carla Bruni-Sarkozy, it is one of the most ambitious campaigns ever, intended to mobilise the global community to provide access to treatment for every mother who needs it. The aim is that, by 2015, no child will be born with HIV.

Most men in Mt Darwin are shying away from circumcision because the physician conducting the operations is a woman. Karanda Hospital in the area is one of the centres designated to offer circumcision on a pilot basis, but only two men have so far undergone the 30-minute operation. Reports show that the majority of men in Mt Darwin and surrounding areas are allegedly shying away from the female physician. The two men who were circumcised by the woman physician are aged 20 and 24.

The highest number of men, 1 898, was circumcised at the Zimbabwe National Family Planning Council site in Harare, which pioneered the programme. Bulawayo, with 1 531, recorded the second highest number of men who opted for the operation. Mutare and Makonde sites circumcised 233 and 86 men respectively.

Presenting an update on the male circumcision project, the national HIV prevention co-ordinator in the Aids and Tuberculosis Unit of the Ministry of Health and Child Welfare, Ms Getrude Ncube, last Friday said the Karanda example was one of the reasons why the pilot programme failed to circumcise one million men, which Government had targeted.

The risk of HIV transmission during anal intercourse may be around 18 times greater than during vaginal intercourse, according to the results of a meta-analysis published online ahead of print in the International Journal of Epidemiology.

Moreover, as well as this empirical work the researchers from Imperial College and the London School of Hygiene and Tropical Medicine carried out a modelling exercise to estimate the impact that HIV treatment has on infectiousness during anal intercourse. They estimate that the risk of transmission from a man with suppressed viral load may be reduced by as much as 99.9%.

Anal intercourse drives the HIV epidemic amongst gay and bisexual men. Moreover a substantial proportion of heterosexuals have anal sex but tend to use condoms less frequently than for vaginal sex, and this may contribute to heterosexual epidemics in sub-Saharan Africa and elsewhere.

Rebecca Baggaley and colleagues conducted a systematic review and meta-analysis (an analysis of all the medical research that meets predefined requirements) of the risk of HIV transmission during unprotected anal intercourse. The same authors have already conducted similar reviews of the transmission risk during vaginal sex and oral sex.

To read the study in the International Journal of Epidemiology, click here.

President Barack Obama renewed his call for increased testing in recognition of National HIV Testing Day this Sunday, noting that one in five people with HIV are unaware they carry the virus.

"In recent years, we have made huge advances in HIV research, prevention and care," he said in a statement Friday. "Still, HIV and AIDS remains an epidemic in this country. That is why my Administration is launching in the coming days a comprehensive National HIV/AIDS Strategy focused on reducing new HIV infections, increasing access to care, and reducing HIV-related health disparities."

Obama also called for businesses, faith groups, scientists, academia, and philanthropic organizations to commit to fighting the epidemic. "And all of us have a responsibility to reduce our risk and know our status, to continue to support those already affected by this disease, and to fight the stigma and discrimination people still face," he added. "So on this National HIV Testing Day, let us all recommit to do our part to help stop the spread of HIV and AIDS."

See also:
Statement by the President on National HIV Testing Day
Statement from Secretary Sebelius on National HIV Testing Day
Statement of Anthony S. Fauci, M.D. Director, National Institute of Allergy and Infectious Diseases National Institutes of Health on National HIV Testing Day June 27, 2010

The weak economy is ravaging the government program that provides life-sustaining antiretroviral drugs to people with H.I.V. or AIDS who cannot afford them. Nearly 1,800 have been relegated to rapidly expanding waiting lists that less than three years ago had dwindled to zero. As with other safety-net programs, ballooning demand caused by persistent unemployment and loss of health insurance is being met with reductions in government resources. Without reliable access to the medications, which cost individuals in the AIDS Drug Assistance Program an average of $12,000 a year, people with H.I.V. are more likely to develop full-blown AIDS, transmit the virus and require expensive hospitalizations.

Eleven states have closed enrollment in the federal program, most recently Florida, which has the nation's third-largest population of people with H.I.V. Three other states have narrowed eligibility, and two of them -- Arkansas and Utah -- have dropped scores of people from the program. Last week, because of swelling numbers here in South Florida, the nationwide waiting list surged past record levels set in 2004, to 1,781 people, according to the National Alliance of State and Territorial AIDS Directors. The growth is expected to continue when Georgia starts deferring enrollment in its drug assistance program on July 1, and Illinois may soon follow.

Thousands of patients who are becoming clinically eligible for anti-retroviral treatment (ART) in Uganda risk early death unless an informal ban on enrollment of new patients by the ART treatment centres countrywide is lifted. Several organisations caring for people living with HIV/AIDS in Uganda have sounded alarm bells regarding their members who are being turned away at anti-retroviral treatment centres even when their CD4 counts (which determine patient immunity levels) show that they are due for treatment. An evening television news report on NTV Uganda on June 16 June, 2010 highlights the plight of hundreds of people with HIV/AIDS who are stranded at treatment centres which have declined to enroll them on treatment citing severe funding dilemmas for the lifelong ART drugs. For people with HIV/AIDS, anti-retroviral treatment is the main hope of prolonging life.

Statistics on the prevalence of HIV/AIDS in the Middle East are hard to come by but a new study launched on 28 June in the United Arab Emirates has attempted to gather all existing data into one place and add some analysis and action points for policymakers.

"In all previous reports we thought there was no HIV data from this region. But there turned out to be lots of data here," said Laith Abu Raddad, director of the Biostatistics and Biomathematic Research Core at Weill Cornell Medical College in Qatar and the principal author of the study (not yet available online). "This report is basically more like a scientific epidemiological study: Getting pieces of data, thousands of data that we managed to collect from every country in the region, putting them together and analysing them to see what they tell us in terms of HIV epidemiology," he said.

See UNAIDS press release: Leaders call for strengthened response to the HIV epidemic in the Middle East and North Africa

The Ugandan government will begin a nationwide male circumcision programme in July as part of its HIV prevention strategy, a senior government official has said. "We now have a national vision on how to move forward, and a government policy and communication strategy will be launched in July," said Dr Alex Opio, assistant commissioner for health services in the Ministry of Health. "Circumcision will be carried out in national referral hospitals, district hospitals and health centre IVs [county level health centres] which have the capacity to conduct minor surgeries."

Why the delay?
The government began drafting the policy in 2008 and there has been criticism of the delay in launching the circumcision programme. In terms of the National AIDS Strategic Plan 2007/8-2011/12, at least 160,000 men should have been circumcised by the end of 2010. It had taken time to get all the government's ducks in a row. "We needed funding; PEPFAR [the United States President's Emergency Plan for AIDS Relief] has stepped in to give the ministry and its partners US$5 million for male circumcision over the next year," Opio said.

Dr Mitch Besser, founder and medical director of the Cape Town based programme, mothers2mothers, (m2m) has received the 2010 Award for Best Practices in Global Health for initiatives to reduce mother-to-child transmission of HIV and provide care to women living with HIV. The Global Health Council Award was presented at the Council's 37th Annual International Conference on Global Health in Washington DC.

The Award for Best Practices is given annually to highlight the efforts of individuals dedicated to improving the health of disadvantaged and disenfranchised populations, and recognide programs that demonstrate the links between health, poverty and development. Besser founded mothers2mothers with one site in South Africa in 2001. It has grown to more than 645 sites in South Africa, Kenya, Lesotho, Malawi, Rwanda, Swaziland and Zambia. The programme employs over 1 600 HIV-positive women who conduct more than 200 000 client interactions per month. In 2009, mothers2mothers enrolled nearly 300 000 pregnant women and new mothers living with HIV as clients.

Researchers conducting clinical trials to search for a microbicide that can help prevent HIV infection in women in Africa and other parts of the world often battle with negative perceptions surrounding their work. Zimbabwe has a number of HIV prevention studies that are being conducted. One of the biggest studies taking place is known as the Vaginal and Oral Interventions to Control the Epidemic (Voice). The study seeks to establish whether an Antiretroviral (ARV) drug taken either as a vaginal microbicide gel or as an oral tablet by HIV-negative women every day before sex can prevent new infections.

Senior Reporter Bertha Shoko (BS) spoke to researcher and director of the Microbicides Trials Network, which operates under the auspices of the University of Zimbabwe in collaboration with the University of California-San Francisco (UZ-UCSF) Nyaradzo Mgodi (NM) to establish the ethical considerations taken before the research and guarantees for protection given to women before they take part in the clinical trials.

BS: Are microbicides currently available for use by women?
NM: No. Scientists are currently testing many substances to see whether they help protect against HIV or other sexually transmitted diseases (STIs) but no safe and effective microbicide is currently available to the public. However, scientists are seriously pursuing dozens of product leads, including 16 that have proven safe and effective in animals and are now being tested in people. If one of these leads proves successful, and with sufficient investment, a successful microbicide could be on the market by the end of the decade.

In the current issue of the Journal, Bettina Salle and coworkers describe infection of female macaques after atraumatic instillation of simian immunodeficiency virus (SIV)-infected cells into the vaginal cavity. This new SIV infection model represents a significant advance for human immunodeficiency virus (HIV) transmission and prevention research. Whereas HIV-infected cells in genital secretions ("Trojan Horse leukocytes") may play an important role in the sexual transmission of HIV, they have been largely overlooked in recent studies on mechanisms of HIV transmission and in the design and testing of HIV vaccine and microbicide candidates. Current preclinical assays for the development of HIV prevention drugs and vaccines predominately use cell-free viral stocks, and the most popular macaque vaginal SIV transmission models used for vaccine and microbicide preclinical efficacy trials require superphysiological doses of cell-free virus and treatment with high doses of progestins to achieve high infection rates. Because the molecular events underlying cell-associated transmission differ from those involved in cell-free virus transmission, many of the current vaccine and microbicide candidates shown to be effective against cell-free virus may not protect against cell-associated viral transmission. The failure of several recent vaccine and microbicide clinical trials to prevent HIV transmission may be due, in part, to this oversight.

See study: Infection of macaques after vaginal exposure to cell-associated simian immunodeficiency virus.

Background Mother-to-child transmission of HIV (MTCT) accounts for over 95% of all paediatric HIV infections worldwide. Several studies have shown that male participation in the antenatal care of their spouses together with couple counselling and testing for HIV, increases use of the interventions for HIV prevention. The prevention programme of MTCT (PMTCT) was launched in Uganda in 2000 and Mbale in 2002. Less than 10% of the pregnant women accepted antenatal HIV testing at Mbale Regional Referral Hospital in 2003; couple counselling and testing for HIV was low. Therefore, we conducted the study to determine the level of male involvement and identify its determinants in the PMTCT programme.

Methods A cross-sectional survey of 388 men aged 18 years or more, whose spouses were attending antenatal care at Mbale Regional Referral Hospital, was conducted in Mbale district, Eastern Uganda. A male involvement index was constructed based on 6 questions. The survey was complemented by eight focus group discussions and five in-depth interviews.

Results The respondents had a median age of 32 years (inter-quartile range, IQR: 28-37). The majority (74%) had a low male involvement index and only 5% of men accompanied their spouses to the antenatal clinic. Men who had attained secondary education were more likely to have a high male involvement index (OR: 1.9, 95% CI: 1.1-3.3) than those who had primary or no formal education. The respondents, whose occupation was driver (OR: 0.3, 95% CI: 0.1-0.7) or those who had fear of disclosure of their HIV sero-status results to their spouses (OR: 0.4, 95% CI: 0.2-0.8), were less likely to have a high male involvement index. Barriers to male involvement in the PMTCT programme were related to both the poor health system, to socio-economic factors and to cultural beliefs.

Conclusions Structural and cultural barriers to men's involvement in the PMTCT programme in Mbale district were complex and interrelated. Community sensitization of men about the benefits of antenatal care and PMTCT and improving client-friendliness in the clinics needs to be prioritised in order to improve low male participation and mitigate the effect of socio-economic and cultural factors.

Objectives The serologic testing algorithm for recent HIV seroconversion (STARHS) calculates incidence using the proportion of testers who produce a level of HIV antibody high enough to be detected by ELISA but low enough to suggest recent infection. The validity of STARHS relies on independence between dates of HIV infection and dates of antibody testing. When subjects choose the time of their own test, testing may be motivated by risky behaviour or symptoms of infection and the criterion may not be met. This analysis was conducted to ascertain whether estimates of incidence derived using STARHS were consistent with estimates derived using a method more robust against motivated testing.

Methods A cohort-based incidence estimator and two STARHS methods were applied to identical populations (n=3821) tested for HIV antibody at publicly funded sites in Seattle. Overall seroincidence estimates, demographically stratified estimates and incidence rate ratios were compared across methods. The proportion of low-antibody testers among HIV-infected individuals was compared with the proportion expected given their testing histories.

Results STARHS estimates generally exceeded cohort-based estimates. Incidence ratios derived using STARHS between demographic strata were not consistent across methods. The proportion of HIV-infected individuals with lower antibody levels exceeded that which would be expected under independence between infection and testing.

Conclusions Incidence estimates and incidence rate ratios derived using methods that rely on the changing antibody level over the course of HIV infection may be vulnerable to bias when applied to populations who choose the time of their own testing.

Men who have sex with men (MSM) have borne a disproportionate burden of human immunodeficiency virus (HIV) infection and remain a markedly underresourced population globally. To better describe HIV epidemics among MSM in low- and middle-income countries, the authors conducted a systematic review of published and unpublished literature available after January 1, 2000 (2000-2009). A total of 133 HIV prevalence studies from 50 countries met the search criteria. Data were used to develop an algorithmic approach to categorize these epidemics. The authors found that the HIV epidemic in low- and middle-income countries may be described using the following 4 scenarios: 1) settings where MSM are the predominant contributor to HIV cases; 2) settings where HIV transmission among MSM occurs in the context of epidemics driven by injection drug users; 3) settings where HIV transmission among MSM occurs in the context of well-established HIV transmission among heterosexuals; and 4) settings where both sexual and parenteral modes contribute significantly to HIV transmission. The authors focused on Peru, Ukraine, Kenya, and Thailand to describe the diversity across and similarities between proposed epidemic scenarios. This scenario-based categorization of HIV epidemics among MSM may assist public health agencies and civil societies to develop and implement better-targeted HIV prevention programs and interventions.

An international multicenter study was conducted to assess the performance of a panel of simian immunodeficiency virus (SIV) RNA reference materials for plasma viral load determinations. Reliable quantification was demonstrated across an ~6 log[10] dynamic range. Availability of external reference materials will enable independent calibration of SIV plasma viral load assays.

An effective HIV vaccine will likely need to reduce mucosal transmission and, if infection occurs, control virus replication. To determine whether our best SIV vaccine can achieve these lofty goals, we vaccinated eight Indian rhesus macaques with SIVmac[delta]239nef and challenged them intrarectally (i.r.) with repeated, low doses of the pathogenic heterologous swarm isolate SIVsmE660. We detected a significant reduction in acquisition of SIVsmE660 in comparison to naïve controls (Log-rank test; p=0.023). After ten mucosal challenges we detected replication of the challenge strain in only five of the eight vaccinated animals. In contrast, seven of the eight control animals became infected with SIVsmE660 after these ten challenges. Additionally, the SIVsmE660-infected vaccinated animals controlled peak acute virus replication significantly better than the naive controls (Mann-Whitney test; p=0.038). Four of the five SIVsmE660 vaccinees rapidly brought virus replication under control by week 4 post-infection. Unfortunately, two of these four vaccinated animals lost control of virus replication during the chronic phase of infection. Bulk sequencing analysis of the circulating virus in these animals indicated that recombination had occurred between the vaccine and challenge strains and likely contributed to the increased virus replication in these animals. Overall, our results suggest that a well-designed HIV vaccine might both reduce the rate of acquisition and control viral replication.

The IFN-inducible antiviral protein tetherin (or BST-2/CD317/HM1.24) impairs release of mature HIV-1 particles from infected cells. HIV-1 Vpu antagonizes the effect of tetherin. The fate of virions trapped at the cell surface remains poorly understood. Here, we asked whether tetherin impairs HIV cell-to-cell transmission, a major means of viral spread. Tetherin-positive or -negative cells, infected with wild-type or [delta]Vpu HIV, were used as donor cells and cocultivated with target lymphocytes. We show that tetherin inhibits productive cell-to-cell transmission of [delta]Vpu to targets and impairs that of WT HIV. Tetherin accumulates with Gag at the contact zone between infected and target cells, but does not prevent the formation of virological synapses. In the presence of tetherin, viruses are then mostly transferred to targets as abnormally large patches. These viral aggregates do not efficiently promote infection after transfer, because they accumulate at the surface of target cells and are impaired in their fusion capacities. Tetherin, by imprinting virions in donor cells, is the first example of a surface restriction factor limiting viral cell-to-cell spread.

The prominent role of antiviral cytotoxic CD8+ T-lymphocytes (CD8-TL) in containing the acute viremia of human and simian immunodeficiency viruses (HIV-1 and SIV) has rationalized the development of T-cell-based vaccines. However, the presence of escape mutations in the acute stage of infection has raised a concern that accelerated escape from vaccine-induced CD8-TL responses might undermine vaccine efficacy. We reanalyzed previously published data of 101,822 viral genomes of three CD8-TL epitopes, Nef103-111RM9 (RM9), Tat28-35SL8 (SL8), and Gag181-189CM9 (CM9), sampled by ultradeep pyrosequencing from eight macaques. Multiple epitope variants appeared during the resolution of acute viremia, followed by the predominance of a single mutant epitope. By fitting a mathematical model, we estimated the first acute escape rate as 0.36 day-1 within escape-prone epitopes, RM9 and SL8, and the chronic escape rate as 0.014 day-1 within the CM9 epitope. Our estimate of SIV acute escape rates was found to be comparable to very early HIV-1 escape rates. The timing of the first escape was more highly correlated with the timing of the peak CD8-TL response than with the magnitude of the CD8-TL response. The transmitted epitope decayed more than 400 times faster during the acute viral decline stage than predicted by a neutral evolution model. However, the founder epitope persisted as a minor population even at the viral set point; in contrast, the majority of acute escape epitopes were completely cleared. Our results suggest that a reservoir of SIV infection is preferentially formed by virus with the transmitted epitope.

Background The contribution of infected semen cells to sexual transmission of human immunodeficiency virus (HIV) is still debated. We addressed this issue in the model of experimental infection of macaques with simian immunodeficiency virus (SIV).

Methods Frozen stocks of cells obtained from the spleen of macaques at the peak of SIVmac251 viremia were prepared. After being thawed and washed, cells were deposited at different concentrations in the vaginas of adult macaques treated with medroxyprogesterone acetate (Depo-Provera). To unravel mechanisms of infection, stock cells labeled with carboxyfluorescein diacetate succinimidyl ester (CFSE) were inoculated intravaginally. Follow-up testing of samples from the mucosa and different lymphoid tissues obtained 21 and 45 h later was performed by flow cytometry, immunohistochemical analysis, and in situ hybridization.

Results Systemic and persistent infection was achieved after vaginal exposure of macaques to SIV-infected cells. The dose needed to infect 50% of females was viral DNA copies. At days 1 and 2 after exposure to cell-associated SIV labeled with CFSE, SIV-positive cells were detected in proximal and distal lymphoid tissues.

Conclusions Infection with SIV after exposure of vaginal and cervical mucosa to cell-associated virus represents a new mechanism of sexual transmission of HIV and SIV that may have significant impacts in the development of preventive approaches like microbicides.

See editorial commentary by Deborah Anderson: Finally, a macaque model for cell-associated SIV/HIV vaginal transmission

A novel approach to supporting health product research and development (R&D) and access in Africa is urgently needed. Successful implementation of such an endeavor requires sustainable capacity, infrastructure, funding, leadership, and an understanding of the status of health R&D in the African continent.

As part of the development of the African Network for Drugs and Diagnostics Innovation (ANDI), we analyzed biomedical research output and collaborative research undertaken across the continent by evaluating peer-reviewed articles published between 2004 and 2008, as well as other innovation indicators, such as R&D investments and manufacturing capacity.

Significant health R&D capacity exists in different parts of Africa, but this capacity is fragmented, uncoordinated, and not properly utilized to address African health problems. Most biomedical collaborations of African institutions are with institutions in Europe and the United States rather than with other African institutions. This lack of intracontinental collaboration, combined with low levels of investment, contributes to gaps in the continental research agenda, a lack of local ownership of research undertaken on the continent, and suboptimal utilization of available research capability. We discuss the establishment of ANDI as a new approach to address these challenges, through the creation, coordination, and funding of African health R&D networks focused on the discovery, development, and delivery of tools to address Africa's unique health needs.

One of the main challenges of developing an HIV-1 vaccine lies in eliciting immune responses that can overcome the antigenic variability exhibited by HIV. Most HIV-1 vaccine development has focused on inducing immunity to conserved regions of the HIV-1 envelope. However, new studies of the sequence-variable regions of the HIV-1 gp120 envelope glycoprotein have shown that there are conserved immunological and structural features in these regions. Recombinant immunogens that include these features may provide the means to address the antigenic diversity of HIV-1 and induce protective antibodies that can prevent infection with HIV-1.

In December 2009, UNAIDS Executive Director Michel Sidibe called for a "prevention revolution" and announced the formation of a UNAIDS High Level Commission on HIV Prevention. The Commission, composed of political, business, activist and philanthropic leaders, will lead a political action campaign over the coming year to galvanize commitment at the highest level in support of effective HIV prevention programmes. The Commission will be launched at the International AIDS Conference in Vienna, Austria on 21 July 2010. Ahead of the launch, the Commission's Co-chairs, Professor Francoise Barre-Sinoussi, Nobel Prize Laureate in Medicine for her role in the discovery of HIV, and Archbishop Emeritus Desmond Tutu, have endorsed a statement, prepared by the Commission's Scientific Advisory Panel, calling for renewed leadership and intensified action to prevent new HIV infections.

EDCTP is pleased to announce the release of its 2009 annual report. 2009 was a very prolific year for EDCTP. This annual report features the rapidly increasing trajectory of EDCTP funded projects including the new grant scheme of European Member State Initiated (MSI) projects and the regional networks of Excellence. This report provides a snap shot of EDCTP funding in sub-Saharan Africa as of end of 2009, highlights of ongoing projects, progress on integration of projects, EDCTP constituency updates, as well as the Fifth EDCTP Forum in Arusha, Tanzania, on 12 to 14 October 2009, among other topics. The 2009 Annual Report also includes a summary in French and Portuguese.

Download the EDCTP Annual Report 2009 (PDF)

The International AIDS Vaccine Initiative (IAVI) announced today that the Government of Japan pledged a US$10 million grant to support AIDS vaccine research and development over the next five years. The grant, which will be channeled through a newly established World Bank trust fund, is the first of its kind from the Japanese government to IAVI.

"We are extremely grateful to Japan for its generous contribution to AIDS vaccine research and development, and also to the World Bank for its untiring support to IAVI and the fight against HIV/AIDS," said Seth Berkley, President and CEO of IAVI. "Japan has been a leader in the fight against infectious diseases and has the scientific capacity to help advance research for one of the toughest public health challenges we face today, the control and ultimate elimination of HIV/AIDS," Berkley added.

With funds from Japan, IAVI, in collaboration with its Japanese partners, will continue to advance an AIDS vaccine candidate that is constructed using a paramyxovirus known as the Sendai virus. Viral vectors based on the Sendai family have the potential to elicit a durable and highly-targeted immune response in mucosal tissues, where HIV often establishes infection before it amplifies and spreads.

PAR-10-219, AIDS International Training and Research Program (AITRP) (D43)
Opening Date: July 16, 2010 (Earliest date an application may be submitted to Grants.gov)
Letters of Intent Submission Date(s): July 16, 2010; July 16, 2011; July 16, 2012
Purpose: The Fogarty International Center (FIC), together with the National Cancer Institute (NCI), the National Institute of Allergy and Infectious Diseases (NIAID), the National Institute of Drug Abuse (NIDA), the National Institute of Dental and Craniofacial Research (NIDCR), and the National Institute of Nursing Research (NINR), encourages renewal and new applications in the AIDS International Training and Research Program (AITRP). The application must propose a collaborative research training program that will strengthen the capacity of institutions in low-and middle-income countries (LMIC), defined by the World Bank classification system, to conduct HIV-related research.

PAR-10-218, Phase II IICOHRTA AIDS/TB Research Training Program (U2R)
Opening Date: July 16, 2010 (Earliest date an application may be submitted to Grants.gov)
Letters of Intent Submission Date(s): July 16, 2010; July 16, 2011; July 16, 2012
Purpose: The Fogarty International Center (FIC), together with the National Institute of Allergy and Infectious Diseases (NIAID), the National Institute of Drug Abuse (NIDA), and the National Institute of Dental and Craniofacial Research (NIDCR), encourages renewal and new applications in the Phase II International Implementation, Clinical, Operations and Health Services Research Training Award for AIDS and TB (IICOHRTA AIDS/TB) program.   Applications must propose, in an integrated manner, a collaborative research training program that will strengthen the capacity of institutions in low-and middle-income countries (LMIC), defined by the World Bank classification system, to conduct HIV and/or tuberculosis implementation  research.

RFA-AI-10-009, Martin Delaney Collaboratory: Towards an HIV-1 Cure (U19)
Letters of Intent Receipt Date: October 4, 2010
Application Receipt Dates: November 4, 2010
Purpose: The National Institute of Allergy and Infectious Diseases (NIAID) and the National Institute of Mental Health (NIMH), National Institutes of Health (NIH), encourage grant applications from institutions/organizations to address the problem of HIV-1 persistence in HIV-1-infected persons treated with suppressive antiretroviral drug regimens.  This FOA will support research in four areas:  (1) basic research to identify and characterize the cellular reservoirs of HIV-1 in treated individuals, (2) development of assays that are physiologically relevant and that comprise a spectrum of cell types that may harbor latent HIV-1 or permit viral replication in the presence of effective antiretroviral drug regimens, (3)  screening of drug candidates that target latent/persistent HIV-1, and (4) development and initial testing of new agents or strategies aimed at the eradication of HIV-1. The goal of this initiative is to expand the knowledge base on HIV-1 latency and persistence so that eradication strategies can be designed, developed and evaluated.  The application must include basic research and translational activities as essential components, and collaborators must include a private sector entity. 

RFA-AI-10-014, Ancillary Studies in Immunomodulation Clinical Trials (R01)
Letters of Intent Receipt Date(s): Thirty days prior to application receipt date
Application Due Date(s): September 9, 2010; December 9, 2010, and March 9, 2011
Purpose: This FOA invites R01 applications for mechanistic studies in clinical trials of: (1) immunomodulatory interventions for immune system mediated diseases, including, but not limited to: asthma and allergic diseases; graft rejection in solid organ, cell, and tissue transplantation; graft versus host disease in hematopoietic stem cell transplantation; and chronic inflammatory, autoimmune, and immunodeficiency diseases; and (2) preventative and therapeutic, vaccines for non-HIV/AIDS infectious diseases, including NIAID Category A, B, and C agents of bioterrorism and emerging/re-emerging infectious diseases. This FOA is a renewal with modifications of RFA AI-08-011 (http://grants.nih.gov/grants/guide/rfa-files/RFA-AI-08-011.html). In order to review and confer awards to grant applications received in response to this FOA in a timely fashion, without delay of the parent clinical trial, applications submitted in response to the FOA will be subject to an accelerated review/award process. Highly meritorious applications selected for funding under this FOA may receive their awards as early as thirteen weeks after the application receipt date.

By mutual agreement, the International AIDS Society and Ms. Gorna have decided to conclude Ms. Gorna's term of service as Executive Director of the IAS. Both Ms. Gorna and the IAS Governing Council have the utmost respect for each other's work and outstanding contributions to the fight against AIDS. The IAS has requested that Ms. Gorna supports the organisation with leadership transition as an expert advisor to the end of 2010. The IAS Governing Council appointed Mats Ahnlund as Acting Executive Director. Ahnlund has been with the IAS since 2003, serving as Conference Director for more than seven years and as Deputy Executive Director for the past nine months. IAS Senior Manager for Congress & Exhibition, Anouk Rey, who has been with the IAS for 6 years and overseen logistics for the last 6 conferences, will serve as Acting Conference Director.

By Carl W. Dieffenbach, Ph.D., Director of NIAID's Division of AIDS
As we begin to discuss the restructuring of NIAID's clinical trials networks, let us first focus on the Institute's HIV prevention research agenda. Developing new biomedical tools that can safely and effectively prevent HIV acquisition and transmission is critical to addressing the global HIV/AIDS pandemic. Currently, we are exploring several promising HIV prevention strategies that, if proven successful, could have a significant impact on reducing the incidence of new infections. These strategies include microbicides -- gels, foams, creams, and other formulations designed to prevent sexual transmission of HIV -- and pre-exposure prophylaxis (PrEP), attempting to block HIV infection by providing antiretroviral medicines to people who are not infected with HIV but who are at high risk for infection. HIV vaccines are also a major focus of our prevention research efforts, but we will discuss that area specifically in an upcoming blog post.

Vaginally or rectally applied microbicides could potentially provide women and men with a means of protecting themselves against sexually transmitted HIV infection. Non-human primate studies have shown that antiretroviral -based microbicides protect against HIV infection, and these types of products are now being tested in people. Nearly a dozen clinical studies are currently evaluating different microbicide candidates and delivery methods, such as the VOICE trial, which is comparing oral antiretroviral medicines to an antiretroviral-based topical gel for HIV prevention. That study is being conducted by the NIAID-supported Microbicide Trials Network. Future microbicide research efforts will focus on evaluating new products, formulations and routes of administration with the goal of finding a safe and effective microbicide that is reliably used by its intended population.

See also:
Looking ahead: NIAID's future HIV/AIDS therapeutics priorities

amfAR, The Foundation for AIDS Research, is pleased to announce the availability of support for Mathilde Krim Fellowships in Basic Biomedical Research. The goal of amfAR's Mathilde Krim Fellows in Basic Biomedical Research program is to provide funding for exceptional researchers who are new to the HIV/AIDS field. Krim Fellowship funding will support the successful applicant's ongoing HIV research and facilitate the transition to a productive and independent long-term career in the HIV/AIDS biomedical research field.

The Krim Fellowship provides support for two years of postdoctoral research, with the possibility of one additional year of research support during the first year of a tenure-track position. Each fellowship is funded at a total of up to $125,000 (phase I): A direct cost maximum of $110,000 is allowed for personnel (salary and fringe benefits) and other research-related expenses. The period of performance for Mathilde Krim Fellowships awarded under this RFP will be from January 1, 2011, to December 31, 2012. LOI forms and research plan due no later than July 16, 2010, 5:00 PM EDT.

You are invited to be part of the Global Forum on MSM and HIV (MSMGF) Survey on HIV Prevention Strategies Targeting Gay Men and Men Who Have Sex with Men (MSM). We are looking for gay men, MSM, and providers from all over the world to take part so that we are able to better understand the HIV prevention knowledge and needs of MSM globally. We are also interested in hearing about the social realities for MSM in your area. The survey should take about 10 minutes to complete. It is available at the following links (please select the language you prefer):

English: https://www.surveymonkey.com/s/HCTXTQ3
Spanish: https://www.surveymonkey.com/s/JPBFQRH
French: https://www.surveymonkey.com/s/JPG3M7S
Russian: https://www.surveymonkey.com/s/JPH7HDK

Preliminary survey findings will be shared at the MSMGF's "Be Heard" Pre-Conference on July 17th in Vienna, Austria. We will also be publishing and disseminating a more extensive report on the findings later this year. Your participation will ensure that we communicate the broadest and most in-depth information possible regarding MSM HIV prevention knowledge and needs. Please send questions to Pato Hebert at phebert@msmgf.org.

This year the IAS Conference it will take place in Vienna, Austria, 18-23 July and bring together nearly 25,000 activists, researchers, policy makers and government officials. AVAC has assembled a "roadmap" with information on sessions and events of interest for HIV prevention research advocates. For the most up-to-date version of the roadmap, visit http://www.avac.org/aids2010. Planning an event on a topic related to HIV prevention research? Email us the details at avac@avac.org, and we'll add it to the map. For more information on the conference visit www.aids2010.org.

Dartmouth Medical School (DMS) and researchers from around the world will offer a look at current efforts to treat and prevent HIV and AIDS, during a public forum at Dartmouth-Hitchcock Medical Center (DHMC) on Friday, July 2. The discussion of "The Forgotten Epidemic: AIDS in the 21st Century" will take place in auditorium G -- where seating is limited. It will run from 1:00 to 4:00 p.m. on the last day of a three-day international conference that DMS and the National Institutes of Health are cohosting for microbiologists, pediatricians, immunologists, obstetricians and gynecologists, physiologists, and civic leaders about advances against the disease.

Speakers at the forum will include Charles R. Wira, Ph.D., a DMS professor of physiology and neurobiology and a coorganizer of the conference, and Dawn Averitt Bridge, an HIV/AIDS survivor of more than two decades. Earlier this year, President Barack Obama appointed Bridge to the Presidential Advisory Council on HIV/AIDS along with Dartmouth College President Jim Yong Kim, M.D., Ph.D, a former director of the Department of HIV/AIDS for the World Health Organization (WHO).

The forum will be broadcast live as a stream and as a podcast following the session. The link to the broadcast is: http://www.dhslides.org/MIC/default.asp.

RFA Number 674-10-00040
The United States Government, as represented by the United States Agency for International Development (USAID) Mission to Southern Africa, is seeking applications from organizations interested to implement a five-year Prevention of Mother-to-Child Transmission (PMTCT) of HIV program in the Kingdom of Swaziland as fully described in this Request for Applications (RFA). The purpose of this Cooperative Agreement is to implement activities involving effective and tested approaches to providing comprehensive and integrated HIV/AIDS care and treatment, and including activities being provided under the current PEPFAR prevention of mother-to-child transmission (PMTCT) program which will contribute to the Government of Swaziland's (GKOS) goals of women, children and prevention being national priority for addressing the HIV epidemic in Swaziland. Closing date for applications is July 20, 2010.

Funding Opportunity Number: WH-MPP-10-001 
For this program, the term "capacity building assistance" or "CBA" means the provision of free (not for fee) information, training, technical assistance (TA) and technology transfer to individuals, organizations and communities to (1) operate optimally, and (2) increase their capacity to effectively deliver evidence-based interventions and core public health strategies for HIV prevention using gender- responsive strategies for programming implementation. CBA services do not include the direct delivery of HIV prevention services. Because populations disproportionately affected by HIV are also disproportionately affected by other sexually transmitted infections (STI) such as gonorrhea, chlamydia, syphilis, and herpes, CBA should encompass prevention interventions and public health best practices for these diseases and infections when appropriate.

CEL-SCI Corporation and researchers at the Northeastern Ohio Universities Colleges of Medicine and Pharmacy (NEOUCOM) jointly announced today that a LEAPSTM-based vaccine (Ligand Epitope Antigen Presentation System) study has demonstrated the technology's potential using dendritic cells to stimulate the immune system to fight viral illnesses and other diseases. Results of the study were selected for an oral presentation at the Federation of Clinical Immunology Societies (FOCIS) Annual Meeting in Boston, Mass., June 27, 2010, and are to be published in Vaccine, a peer-reviewed journal for vaccines and vaccination. The study showed that it is possible to convert normal mouse bone marrow cells into dendritic cells that can be transferred into other mice to confer 100 percent protection from a 3-4 fold LD50 dose viral (HSV-1) challenge.

The LEAPS vaccine (JgD) contains a peptide from a herpes simplex virus type 1 protein. Dendritic cells activate an immune response which provides protection against HSV disease and death. Most of the mice receiving the JgD treated dendritic cells showed no disease and all survived. In contrast, almost all of the mice receiving no immunization or dendritic cells treated with an HIV vaccine (JH) or other control treatments showed serious disease and died.