10 OCTOBER 2010, VOLUME 11, ISSUE 37

Funding for HIV/AIDS vaccine research is drying up -- just as scientists are claiming "optimism" about their research, a conference has heard. The amount of money going into research has decreased because of the economic downturn and competing global health priorities, Alan Bernstein, executive director of the Global HIV Vaccine Enterprise, told the AIDS Vaccine 2010 conference in the United States this week (28 September-1 October).

Last year's RV144 vaccine trial on 16,000 people in Thailand showed for the first time that a vaccine could cut the risk of HIV infection, and followed years of failure to make progress on vaccines. Phase III trials of this vaccine will be conducted early in 2011 in South Africa and Thailand, Bernstein said at the international meeting.

The Obama administration boosted its pledge to the Global Fund to Fight AIDS, Tuberculosis & Malaria by 38 percent, to $4 billion, while urging changes to make the organization more efficient and more accountable. The contribution brings the total pledge from donor countries to $11.7 billion over three years, the fund said in a statement today. The U.S. money comes with requirements to monitor how well the Global Fund's programs work with local populations, said Eric Goosby, U.S. Global AIDS Coordinator, in a conference call with reporters today. The U.S. will base future donations on the group's effectiveness, Goosy said. President Barack Obama's budget for global health, announced in February, reduced the U.S. pledge to the fund, in favor of expanding programs for child and maternal health. Today's increase signals to other nations that the U.S., the fund's largest donor, remains committed to distributing global health aid through the Geneva-based organization.

See press release issued by U.S. Department of State: "Obama Administration's pledge to Global Fund to Fight HIV/AIDS, malaria and tuberculosis".

UN agencies report that a decline in donor support, due to the current economic downturn, may compromise crucial programs for HIV/AIDS. The report was released before a meeting this week of major donors to the Global Fund to Fight AIDS, Tuberculosis and Malaria. Experts argue that unless more funds are committed, progress on HIV/AIDS will stall or even reverse.

Rozina Chimbalani's daughter died of AIDS, leaving behind two children. Chimbalani now takes care of her grandchildren with money she gets from a government program in Malawi. The program provides funds to families lilke Chimbalani's to meet the needs of children and buy their school supplies. "This project has changed my life. If I didn't get a cash transfer I would be miserable and might even have died by now, and the kids would be on their own," she said.

Researchers attending an AIDS vaccine conference in Atlanta this week are abuzz about broadly neutralizing antibodies and their potential to prevent HIV in monkeys. Broadly neutralizing antibodies are a handful of recently discovered human antibodies that can bind to the AIDS virus and prevent it from infecting cells. New technology is allowing scientists to isolate and study these areas of the human immune system in people who have been infected for years, said Galit Alter, a Canadian HIV researcher who works at the Ragon Institute in Boston. However, the antibodies develop too slowly to help these patients. Also, the antibodies are only found among 10 and 30 per cent of people with long-standing HIV infections. Researchers are now trying to find a vaccine to make the immune system produce the antibodies earlier.

Further Aids vaccine studies will be carried out in Thailand after a recent large-scale clinical trial for the first time offered hope for HIV prevention by vaccination. Researchers are planning to conduct small-scale experiments as early as the middle of next year to carry on from the work conducted in the original RV305 trial. "We're trying to learn as much as possible from the result of the recent vaccine trial and the follow-up studies," said Supachai Rerks-Ngarm, principal investigator of the Phase III HIV/Aids vaccine project. About 160 volunteers, who participated in a vaccine trial from 2003 to 2006, will be called in for the new tests, which are being conducted by the Public Health Ministry, Mahidol University's department of clinical tropical medicine and the US military's HIV research programme.

About 700,000 people signed a petition for more funds to fight HIV which will be handed to UN chief Ban Ki-moon on Monday ahead of a meeting of donors, the Born HIV Free campaign said. The petition calls for the international community to provide the necessary funds to eliminate the transmission of HIV from mothers to children by 2015, Born HIV Free, which is supported by French First Lady Carla Bruni-Sarkozy, said in a statement.

In 2009, 53 percent of women with HIV were treated with antiretroviral drugs to reduce the risk of transmission during pregnancy, childbirth or breastfeeding, according to the campaign. The Born HIV Free campaign had increased public awareness and action in this important part of the fight against AIDS, said Michel Kazatchkine, director of the Global Fund to Fight AIDS, Tuberculosis and Malaria. About 20 million people have watched Born HIV Free's videos on its website and video-sharing site YouTube, the statement said.

Scientists from around the world are meeting in Atlanta, Georgia, this week at the AIDS Vaccine 2010 conference.  Besides discussing the latest research, they're looking for ways to do a better, faster job of finding an effective vaccine to end the pandemic.

Mitchell Warren, head of AVAC, the AIDS Vaccine Advocacy Coalition, says, "This conference is coming at a really interesting time in the search for an AIDS vaccine.  We're almost exactly a year out since we had the report of the success in the Thai prime boost trial (RV144) -- the first evidence of vaccine effect."

"The study results, representing a significant scientific advance, are the first demonstration that a vaccine can prevent HIV infection in a general adult population and are of great importance," said UNAIDS and the WHO last September. Warren says, "It's fascinating to watch the entire field grappling with the bottom line question: What next?....  I must say, in my mind, (there's) even more energy in this conference this year than there was a year ago when the results were announced." That's a "good sign" for the (research) field, according to the AVAC leader, "in terms of scientific debate and discovery."

This week more than a thousand of the world's experts on HIV/AIDS vaccine science gathered in Atlanta to attend AIDS Vaccine 2010, the leading international meeting focused specifically on HIV vaccine research and development. A safe and effective HIV vaccine is needed now more than ever. Despite the tremendous success of AIDS therapies that have greatly extended life expectancy and quality of life for those living with HIV and AIDS, the epidemic continues to spread at an alarming rate.

Each year more than 56,000 people in the U.S. are newly infected with HIV and more than 14,000 people die from AIDS. Globally, HIV is responsible for more than 50,000 new infections each week and for more than 2.5 million new infections each year, with 33 million people now living with the disease. Since the disease was first recognized in 1981, it has claimed over 25 million lives worldwide. The South has been particularly hard hit by HIV, with the highest proportion of new AIDS diagnoses in the country and the highest prevalence of people living with AIDS. It is the only region where the number of HIV/AIDS-related deaths has increased since 2001.

A worldwide search for an effective vaccine against AIDS was launched in Atlanta Wednesday, with international researchers agreeing to work together to speed up their efforts. About 1,100 researchers attending the AIDS Vaccine 2010 conference decided to form a new group called the Global HIV Vaccine Enterprise aimed at coming up with a new vaccine strategy.

Every day, 7,400 people are newly infected with HIV worldwide. Even though vaccines commonly take decades to develop, researchers at the meeting share a sense of urgency that is driving them to look for new ways of doing their work. "Scientists should share data in real time so the breakthroughs coming from one team are rapidly applied across the field," said Jose Esparza, senior advisor for HIV vaccines at the Bill and Melinda Gates Foundation, which pays for a large proportion of the research on AIDS vaccines.

Researchers often guard their work to seek the prestige of publishing their results. But the new strategic plan reflects different priorities and values, said the group's executive director, Dr. Alain Bernstein. Those values include co-operation, collaboration, openness, transparency, sharing data and results quickly across national and institutional barriers, Bernstein said. Bernstein points to the moderately effective RV144 experimental vaccine that was tested in Thailand. Researchers worldwide now have access to the data and blood samples used in that study and can look for ways to make the vaccine more effective, he said.

The preliminary results of the Phase I prime-boost AIDS vaccine trial started in February 2009 and conducted at the Tuberculosis Research Centre (TRC), Chennai and the National AIDS Research Institute (NARI), Pune, has shown that the vaccine used is safe and its ability to elicit immune response is modest. The results were presented yesterday (Sept 29) at the AIDS Vaccine 2010 conference in Atlanta, U.S. The results are based on preliminary, blinded data. Unblinding makes it possible to know who has received the vaccine and who has received the placebo.

The vaccine trial used ADVAX, a DNA-based vaccine, as the prime and Modified Vaccinia Ankara (MVA) as the boost. ADVAX was earlier tested in the U.S. and found to be safe. Similarly, MVA vector, which was earlier tested at TRC in 2008, showed that the vaccine was safe.As on date no serious adverse events were reported by any of the total of 32 volunteers recruited for the trial at both TRC and NARI. Based on this, it can be said that the vaccine is safe.

VIRxSYS Corporation, a privately held company developing vaccines and RNA therapies for serious human diseases, presented results from a study of VRX1116, a simian analog for an investigational, lentiviral-based vaccine for HIV VRX1273, at the AIDS Vaccine 2010 conference in Atlanta, GA. In this prophylactic non human primate study, two out of five monkeys immunized with the vaccine were able to "functionally cure," or fully control and suppress viral replication over time after challenge with a highly pathogenic simian immunodeficiency virus (SIV), and have shown stable or increased CD4 counts compared to pre-challenge baselines Additionally, the death of several monkeys in the control, unvaccinated group showed that VRX1116-based vaccination was capable of conferring a survival benefit following SIV infection. The vaccine was safely and repeatedly administered and proved to be highly immunogenic with sustained immune responses. Virological and immunological benefits, including control of viral load and preservation of the CD4 compartment, were sustained for as long as one year post-challenge.

Profectus BioSciences Inc., a company developing vaccines to treat and prevent chronic viral diseases such as AIDS, has won $3.1 million in National Institute of Health grants. The company also received NIH collaborative grants to Dr. Robert Gallo, director of the Institute of Human Virology of the University of Maryland School of Medicine. The grants support the development of the company's Transition State Vaccine (TSV) technology for a prophylactic HIV Vaccine. The company harnesses the human immune system to treat and prevent viral diseases and cancers via its proprietary vaccines. Originally developed at the IHV, the TSV strategy targets the adaptive immune response to the most protected portions of HIV envelope spikes that are considered the "Achilles heel" of all HIV isolates. The TSV is being developed as a subunit protein and also for delivery utilizing the Company's plasmid DNA and recombinant Vesicular Stomatitis Virus vaccine vectors. Thus far, the TSV approach has generated significant protective responses in several non-human primate models for HIV.

As researchers and policy makers work toward an effective HIV vaccine in a constrained global economy, cost-effective prevention strategies such as Couples Voluntary Counseling and Testing (CVCT) must take a larger role in efforts to decrease the rates of HIV/AIDS in Africa, says Emory University HIV/AIDS vaccine researcher Susan Allen, MD, MPH. Allen presented her research today at the AIDS Vaccine 2010 international conference in Atlanta, sponsored by the Global HIV Vaccine Enterprise and locally hosted by the Emory Center for AIDS Research. Allen, who has worked to combat the AIDS epidemic in Africa for more than 25 years, highlighted the value of CVCT and other cost-effective HIV prevention strategies.

"The majority of new HIV infections are acquired from a spouse, and couples are the largest HIV risk group in Africa," says Allen, a professor of pathology and laboratory medicine in the Emory School of Medicine and adjunct faculty member in the Rollins School of Public Health. "By using CVCT to identify those people who do not share the same HIV status as their spouse or partner, we're in a better place to move forward efficiently and effectively once a vaccine does become available."

ARTES Biotechnology announces today the acquirement of the ANAVAX virus-like particle (VLP) technology from Select Vaccines Ltd. ANAVAX is a patent-protected VLP technology that can be applied to the prevention of several infectious diseases. With the combination of two excellent technology platforms, ANAVAX and the Hansenula expression system, ARTES has positioned itself as a unique partner for the vaccine industry. The ANAVAX VLP platform has already been applied to the development of adjuvant-free vaccines against avian and swine flu, malaria and HIV. Hansenula is the preferred technology for affordable mass vaccination and is recommended by the WHO for hepatitis B vaccination campaigns. Together, the platforms build a new approach to low-cost mass production of safe and effective vaccines. ARTES' business plan is to enhance its position as a preferred development partner for vaccine manufacturer.

The United States National Institutes of Health said on Thursday it will share intellectual property rights on some AIDS drugs in a patent pool designed to make treatments more widely available to the poor. The NIH is the first research institution to join an HIV medicines patent pool launched by UNITAID, a health financing system funded by a tax on airline tickets which was co-founded by Brazil, Britain, Chile, France, and Norway in 2006. A UNITAID official told Reuters in July several major drugmakers, including Merck, Tibotec and Gilead, were in advanced talks on joining the AIDS drug pool. But others -- including GlaxoSmithKline and Pfizer's HIV/AIDS drug joint venture, ViiV Healthcare -- have said they would rather agree their own licensing deals with generic makers in developing countries.

In another signal that the global battle against AIDS is falling apart for lack of money, the Global Fund to Fight AIDS, Tuberculosis and Malaria failed on Tuesday to reach even its lowest "austerity level" fund-raising target of $13 billion -- the amount it had said it needed just to keep putting patients on treatment at current rates. Three-year pledges from 40 countries attending a two-day conference held in Manhattan amounted to $11.7 billion. The pledges were announced at the United Nations. The fund had hoped to raise $20 billion to catch up with the growing epidemic.

No one now on treatment will be cut off, said Dr. Michel Kazatchkine, the fund's executive director, but the targets for the next few years must be lowered. He said that he "deeply appreciates" the amount raised, but that "we need to recognize that it's not enough to meet expected demand and will lead to difficult decisions in the next three years." He could not, he said, estimate exactly how many deaths would result.

The fund pays for AIDS drugs for almost three million patients now, and still might be able to reach four million by 2013. It had hoped to reach five million or more. It supports about half of the world's poor who are getting treatment. The President's Emergency Plan for AIDS Relief, or Pepfar, started under the administration of President George W. Bush, pays for the other half.

The human immunodeficiency virus type-1 (HIV-1) continues its global spread, with an estimated 33 million people infected. The most cost-effective mechanism of infectious disease control is vaccination, but to date vaccine trials have had only modest success at reducing HIV-1 spread.

However, antibodies that block HIV-1 infection, termed neutralizing antibodies (NAbs), are known to be effective in preventing HIV-1 infection. Unfortunately, current vaccines have been unable to induce the host to produce this type of antibody. The immune system mounts an immune response to HIV-1 that includes the production of antibodies that bind the viral envelope glycoprotein (Env), the target of neutralizing antibodies. However, naturally produced antibodies are insufficient to curtail infection in most people. One reason is that the Env gene has a strong propensity to randomly mutate its amino acid sequence, rendering antibodies produced against an early version of the glycoprotein ineffective at binding a subsequent version. Therefore, most NAbs produced by the host will only bind to a small subset of total HIV-1 strains that are produced over the course of an infection.

A record 1.2 million people in low and middle income countries started antiretroviral therapy for HIV/AIDS in 2009, the World Health Organization said on Tuesday, but targets set for 2010 are unlikely to be met. A total of 5.25 million people were receiving antiretroviral therapy in 2009, three-quarters of them in Africa, WHO said in a report co-authored with U.N. children's fund UNICEF and UNAIDS. "Millions of people are alive today as a result of investments in HIV over the past few years," it said, reporting success in "reducing new infections, averting deaths and ensuring that people living with HIV enjoy healthy lives."

The report said eight low and middle income countries -- Botswana, Cambodia, Croatia, Cuba, Guyana, Oman, Romania and Rwanda -- met the goal of giving treatment to at least 80 per cent of patients in need in 2009, well ahead of the end-2010 deadline agreed by world leaders in 2006. However, global targets for HIV prevention, treatment, care and support are unlikely to be reached in 2010, it said.

When a Muslim and a Jewish surgeon travel to KwaZulu Natal later this month to help local healthcare teams develop high-volume adult male circumcision programmes, they are expecting considerable interest. Operation Abraham, an Israel-based group, has tapped into the traditional experience of two faiths in circumcision to offer guidance in a region where the practice was long in abeyance but recently resumed. "Young men are proving very receptive," says Inon Schenker, who led a first training team in August dubbed Shesha (Zulu for swift), based on earlier pilot schemes in Swaziland.

South Africa has long been at the epicentre of the HIV epidemic, and a venue for innovation in tackling the disease. Now, the change in political leadership is allowing some of the findings to be put into practice, albeit more slowly than many advocates would like. Two decades after anecdotal and observational data highlighted lower HIV rates in circumcised men, it was in Orange Farm, near Johannesburg, that Bertran Auvert, a French researcher, conducted a systematic clinical trial proving that the procedure could reduce infection by 60 per cent.

In South Africa's private sector, the findings began soon began to have an impact. "As soon as we saw the data, we made sure adult male circumcision would become a funded benefit," says Jonathan Broomberg, head of Discovery Health, a large health insurance company that has also helped fund Shesha philanthropically. Yet if scientific, logistical, procedural and financial hurdles have helped explain the modest overall progress thus far in many countries, South Africa had a particular political challenge rooted in the ambivalence of Thabo Mbeki, the former president, towards tackling Aids.

Inmates in Zimbabwe's filthy prisons could soon be receiving condoms while in incarceration to prevent the spread of HIV, NewsDay has established. According to proposals by the Ministry of Health and Child Welfare and World Health Organisation (WHO), prisoners could soon benefit from initiatives to curb the spread of the deadly scourge. The director of the Aids and TB programme, Owen Mugurungi, told journalists attending a workshop whose theme was "Understanding multiple concurrent partnerships and male circumcision" in Kadoma that his ministry was working with the Justice ministry to address health challenges in the country's prisons. He said there had been realisation that there was rampant homosexuality in the penitentiaries and upon release the likelihood to affect spouses and girlfriends was high.

An experimental vaccine intended to prevent genital herpes disease in women, although generally safe and well-tolerated, proved ineffective when tested in the recently concluded clinical study known as the Herpevac Trial for Women. The Phase 3 trial, sponsored by GlaxoSmithKline (GSK) Biologicals, based in Belgium, with support from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, began in 2002. A total of 8,323 women aged 18-30 years participated in the trial at 50 sites in the United States and Canada. At the time of their enrollment, the study participants were free of the two types of herpes simplex viruses (HSV), HSV-1 and HSV-2.

Participants in the Herpevac trial were randomly divided into two groups. One group received the candidate vaccine, containing HSV protein along with an adjuvant intended to boost immune responses. The second, control group received a version of Havrix, a licensed vaccine against hepatitis A. This study design gave all participants the potential opportunity to be protected against either genital herpes or hepatitis A. GSK developed the candidate vaccine and also manufactures Havrix. In the Herpevac study, however, the investigational vaccine was ineffective in protecting against genital herpes disease. The estimate of vaccine effectiveness was 20 percent, but all estimates have statistical uncertainty, and this effect was not substantially different from zero.

The success of tests into the effectiveness of anti-HIV gels to be used by women before engaging in sex has presented Zimbabwe with another chance of further reducing the rapid transmission of the virus. According to various presentations made at a feedback workshop organised by the United Nations Population Fund (UNFPA) and the National Aids Council (NAC) on Friday, the research on the gels has brought a lot of hope. One of the gels is based on the anti-retroviral (ARV) drug Tenofovir and recent research carried out in South Africa showed that it reduces transmission of Aids to women if used before sex.

Four former heads of State and other high level African leaders who are the champions for a HIV/AIDS-free generation project are this month expected in the country for an accelerated meeting on response to the HIV epidemic. The champions are coming at the invitation of President Rupiah Banda and will meet Zambia's leaders from October 19 to 21 to share various regional experiences in response to HIV/AIDS.

National AIDS Council (NAC) spokesperson Justine Mwiinga said in Lusaka yesterday that current chairperson, former Botswana president Festus Mogae would lead the delegation. The champions are Mozambique's Joaquim Chissano, Tanzania's Benjamin Mkapa, Zambia's Kenneth Kaunda, former vice-president of Uganda Speciosa Wandira and Kenya's national AIDS control council chairperson, Miriam Were.

Mr Mwiinga said during a media breakfast that the champions would use the meeting to gain insight on progress and challenges towards the scaling up of HIV prevention initiatives in Zambia. He said the champions would further utilise the meeting to explore possible solutions to reduce new infections on HIV/AIDS.  He said Zambia was still faced with six challenges in the fight against HIV/AIDS such as low rate of condoms, low male circumcise and gender based violence and the champions would use it for national response to HIV/AIDS.

Bionor Pharma today reported the main findings of an international, randomized, double-blind, placebo-controlled multi-center phase IIb trial designed to test HIV-patients' ability to stay off their ART (Anti Retroviral Therapy) drugs after having been immunized with the company's therapeutic HIV-vaccine candidate, Vacc-4x. The study did not meet its two primary endpoints. Vacc-4x did not show any clinical effect with regard to number of patients that needed resumption of ART nor did Vacc-4x show any difference in CD4-counts at the end of the ART-free period compared to placebo. Bionor Pharma will allow a full analysis of immunological data from the trial. However, the negative clinical result means the company will not continue development of Vacc-4x but will focus on its other vaccine products in pipeline.

Bioject Medical Technologies Inc., a leading developer of needle-free injection therapy systems, today announced that its unique Needle-Free Injection Therapy (NFIT) system, the Biojector(R) 2000, is being utilized in a study sponsored by the National Institute of Allergy and Infectious Diseases (NIAID) which is part of the U.S. National Institutes of Health (NIH). The Phase Ib study, called RV262, is evaluating a combination DNA prime/MVA vector boost regimen that was developed to protect against diverse subtypes of HIV-1 prevalent in North America, Europe, Africa, Asia and South America. The study is being conducted by the U.S. Military HIV Research Program (MHRP) through its clinical research network in the U.S., East Africa and Thailand.

The study will enroll 92 total participants and is designed to assess safety and immune responses. This clinical trial was designed to test a unique prime-boost preventive HIV vaccination strategy aimed at global coverage. The prime is a plasmid DNA vaccine, PENNVAX(TM)-G, and the boost is a virus vector vaccine, Modified Vaccinia Ankara-Chiang Mai Double Recombinant (MVA-CMDR). Together, the vaccines are designed to deliver a diverse mixture of antigens for HIV-1 subtypes A, B, C, D and E.

The Dana Farber Cancer Institute and the University of Massachusetts Medical School have received $1.15 million in federal grants from the U.S. Department of Health and Human Services' National Institute of Allergy and Infectious Diseases to apply to research on how immune systems fight HIV and other infections. The funding was announced today by U.S. Sen. John Kerry and U.S. Rep. Jim McGovern. The Dana Farber Cancer Institute received a $736,750 grant to study gene response to HIV vaccines. The University of Massachusetts Medical School in Worcester has landed a $411,250 grant for its immune systems research, called "Regulation of conventional versus innate CD8+ T cell development."

Twelve scientific teams in more than a dozen states will receive National Institutes of Health grants to study effective ways to prevent and treat HIV/AIDS among people in the criminal justice system. The grants, announced today, will be awarded primarily by the National Institute on Drug Abuse (NIDA), with additional support from the National Institute of Mental Health (NIMH) and the National Institute of Allergy and Infectious Diseases (NIAID), all components of NIH. The research will take place over a five-year period.

"These important and wide reaching research grants will focus on identifying individuals with HIV within the criminal justice system and linking them to highly active antiretroviral therapy (HAART) during periods of incarceration and after community re-entry," said NIDA Director Dr. Nora D. Volkow. "We hope this effort will lead to decreased HIV/AIDS-related illness and death among those in the criminal justice system, as well as decrease HIV transmission in the community at-large, making an important impact on public health."

The seek, test and treat funding opportunity follows NIH-sponsored research conducted over the last few years which has indicated that identifying and offering treatment to all medically eligible HIV-positive individuals cannot only stop progression to AIDS and AIDS-related death, but can also help to prevent HIV transmission. These new grants will apply this strategy to the criminal justice system, where there is a high prevalence of HIV/AIDS and often poor access to treatment.

Microbicides are a promising approach for the prevention of HIV-1 transmission. Unfortunately, various candidates failed in clinical trials. In some cases, the candidate microbicide even resulted in enhanced virus transmission. Therefore, there is an urgent need to develop more predictive preclinical strategies to anticipate the in vivo efficiency/toxicity rate, including in vitro assays that evaluate effects on epithelial integrity and inflammation. The present study aims to identify potential safety issues concerning the use of microbicides and excipients commonly used in vaginal microbicide preparations. The toxicity of various active pharmaceutical ingredients (APIs) (TMC120, UC-781, PMPA, PRO2000 and GML) and excipients (preservatives, cosolvents, surfactants and cyclodextrins) was evaluated using an in vitro dual-chamber model and uterine cervical explants. Epithelial viability and permeability for fluorescent virus-sized beads, as well as induction of interleukin-8 (as a sensitive marker of an inflammatory response) were assessed. Surprisingly, cell viability and epithelial layer integrity were compromised by most excipients at concentrations near the typical concentration used in vaginal gels and a significant increase in the production of IL-8 was observed at sub-toxic concentrations. Within the API, TMC120, UC-781, PMPA showed a higher selectivity index compared to PRO2000 and GML. In conclusion, identification of safety issues concerning the use of pharmaceutical excipients could help to formulate less toxic vaginal microbicide preparations.

Herpes simplex virus type 2 (HSV-2) is the most common cause of genital ulcer disease and is a cofactor for HIV-1 acquisition and transmission. We analyzed specimens from three separate phase III trials of acyclovir (ACV) for prevention of HIV-1 acquisition and transmission to determine if failure of ACV to interrupt HIV acquisition and transmission was associated with genotypic ACV resistance. Acyclovir (400 mg twice daily) or placebo was provided to HSV-2-infected persons at risk of HIV-1 infection in the Mwanza and HPTN 039 trials and to persons dually infected with HSV-2 and HIV-1 who had an HIV-negative partner in the Partners in Prevention study. We extracted HSV DNA from genital ulcer swabs or cervicovaginal lavage fluids from 68 samples obtained from 64 participants randomized to ACV and sequenced the HSV-2 UL23 gene encoding thymidine kinase. The UL23 sequences were compared with published and unpublished data. Variants were observed in 38/1,128 (3.4%) nucleotide positions in the UL23 open reading frame, with 58% of these encoding amino acid changes. No deletions, insertions, or mutations known to be associated with resistance were detected. Thirty-one of the variants (81.5%) are newly reported, 15 of which code for amino acid changes. Overall, UL23 is highly polymorphic compared to other loci in HSV-2, but no drug resistance mutations were detected that could explain the failure to reduce HIV incidence or to prevent HIV-1 transmission in these studies.

Background Women account for an increasing proportion of patients with HIV-1 but remain underrepresented in antiretroviral clinical trials.

Objective To evaluate sex-based differences in efficacy and adverse events in treatment-experienced, HIV-positive women and men receiving darunavir-ritonavir therapy over 48 weeks.

Design Multicenter, open-label, phase 3b study designed to enroll a high proportion of women, with sample size determined on the basis of a noninferiority design with a maximum allowable difference of 15% in virologic response favoring men. (ClinicalTrials.gov registration number: NCT00381303)

Setting 65 sites in the United States, Puerto Rico, and Canada.

Patients 287 women and 142 men.

Intervention Patients received darunavir-ritonavir, 600/100 mg twice daily, plus an investigator-selected optimized background regimen.

Measurements Virologic response (HIV RNA <50 copies/mL using a time-to-loss of virologic response [TLOVR] algorithm) and adverse events were assessed over 48 weeks.

Results 67% of patients were women; 84% of patients were black or Hispanic. A higher proportion of women discontinued treatment than men (32.8% vs. 23.2%; P = 0.042); more women than men discontinued treatment for reasons other than virologic failure. Response rates in women and men at week 48 were 50.9% and 58.5%, respectively (intention-to-treat TLOVR), and 73.0% and 73.5%, respectively (TLOVR censored for patients who withdrew for reasons other than virologic failure). The absolute difference in response, based on logistic regression and adjusted for baseline log10 viral load and CD4+ cell count, was -9.6 percentage points (95% CI, -19.9 to 0.7 percentage points; P = 0.067) for intention-to-treat TLOVR and -3.9 percentage points (CI, -13.9 to 6.0 percentage points; P = 0.438) for TLOVR population that censored patients who withdrew for reasons other than virologic failure. Adverse events were similar between the sexes. The most common grade 2 to 4 adverse events that were considered at least possibly treatment related in women and men were nausea (5.2% and 2.8%, respectively), diarrhea (4.5% and 4.9%, respectively), and rash (2.1% and 2.8%, respectively).

Limitation Baseline characteristics differed between sexes.

Conclusion Nonsignificant, sex-based differences in response were found during the 48-week study; however, these differences were probably due to higher discontinuation rates in women, suggesting that additional efforts are needed to retain women in clinical trials.

Objectives Numbers of newly diagnosed HIV infections among men who have sex with men (MSM) in Germany increased after the year 2000. We sought to explore trends in STI co-infections around the time of HIV seroconversion in patients from the German HIV-1 seroconverter cohort from 1996-2007.

Methods MSM from the cohort were included for secondary analysis, if seroconversion occurred between 1996 and 2007 and if a blood sample taken within 2 y after HIV infection was available for further testing. Samples were tested for antibodies against Treponema pallidum and HSV-2. A classification system was developed to assign the chronology of syphilis and HIV-1 infection.

Results Data of 1052 MSM were eligible for analysis. Overall seroprevalence of syphilis markers was 26%, increasing from 10% (1996-1999) to 35% (2005). Among HIV seroconverters with positive syphilis antibodies, 32% (n=88) were rated as having had coincident infections with HIV and syphilis. Coincident syphilis infection at HIV diagnosis increased substantially (p<0.001) from 2.3% in 2000 to 16.9% in 2003; and thereafter declined to 4.3% in 2007. Mean HSV-2 antibody prevalence was 40.5%, mean anti-HSV-2 IgM prevalence was 11.2%, with no significant change over time.

Discussion We found a stable prevalence of HSV-2 infection and increasing prevalence of syphilis infection around the time of HIV acquisition among MSM in Germany. Time course and rate of co-infections suggest that a re-emerging syphilis co-epidemic among MSM after 2000 could have contributed to an increase of HIV incidence by enhancing HIV transmission probability.

Introduction The World Health Organization (WHO) published a revision of the antiretroviral therapy (ART) guidelines and now recommends ART for all those with a CD4 cell count <=350/mm3, for people with HIV and active tuberculosis (TB) or chronic active hepatitis B irrespective of CD4 cell count and all HIV-positive pregnant women. A study was undertaken to estimate the impact of the new guidelines using four countries as examples.

Methods The current WHO/UNAIDS country projections were accessed based on the 2007 estimates for Zambia, Kenya, Cameroon and Vietnam. New projections were created using Spectrum. CD4 progression rates to need for ART were modified and compared with the baseline projections.

Results The pattern of increased need for treatment is similar across the four projections. Initiating treatment at a CD4 count <250/mm3 will increase the need for treatment by a median of 22% immediately, initiating ART at a CD4 count <350/mm3 increases the need for treatment by a median of 60%, and the need for treatment doubles if ART is commenced at a CD4 count <500/mm3. Initiating ART at a CD4 cell count <250/mm3 would increase the need for treatment by a median of around 15% in 2012; initiating treatment at a CD4 count <350/mm3 increases the need for treatment by a median of 42% across the same projections and about 84% if CD4 <500/mm3 was used.

Conclusions The projections indicate that initiating ART earlier in the course of the disease by increasing the threshold for the initiation of ART would increase the numbers of adults in need of treatment immediately and in the future.

Maternal HIV-1-specific antibodies are efficiently transferred to newborns, but their role in disease control is unknown. We administered neutralizing IgG, including the human neutralizing monoclonal IgG1b12, at levels insufficient to block infection, to six newborn macaques before oral challenge with simian-HIV strain SF162P3 (SHIVSF162P3). All of the macaques rapidly developed neutralizing antibodies and had significantly reduced plasma viremia for six months. These studies support the use of neutralizing antibodies in enhancing B cell responses and viral control in perinatal settings.

See press release issued by Oregon Health and Science University: "OHSU researchers working on AIDS treatment for babies".

Editor's Note: This special issue presents findings from the National National Survey of Sexual Health and Behavior (NSSHB), Center for Sexual Health Promotion, Indiana University.

Guest Editorial
Background and considerations on the National Survey of Sexual Health and Behavior (NSSHB) from the investigators
Reece M, et al. 

Commentaries
Looking at sexual behavior 60 years after Kinsey
Goldstein I
Sex for health and pleasure throughout a lifetime
Elders MJ
Time for change: rethinking and reframing sexual health in the United States
Fenton KA
Commentary on the National Survey of Sexual Health and Behavior (NSSHB)
Barclay LB

Original Research
Sexual behavior in the United States: results from a national probability sample of men and women ages 14-94
Herbenick D, et al.
Condom use rates in a national probability sample of males and females ages 14 to 94 in the United States
Reece M, et al.
Sexual behaviors, relationships, and perceived health status among adult women in the United States: results from a national probability sample
Herbenick D, et  al.
Sexual behaviors, relationships, and perceived health among adult men in the United States: results from a national probability sample
Reece M, et al.
Sexual behaviors and condom use at last vaginal intercourse: a national sample of adolescents ages 14 to 17 years
Fortenberry JD, et al.
Sexual behaviors, condom use, and sexual health of Americans over 50: implications for sexual health promotion for older adults
Schick V, et al.
Sexual health among U.S. black and Hispanic men and women: a nationally representative study
Dodge B, et al.
An event-level analysis of the sexual characteristics and composition among adults ages 18 to 59: results from a national probability sample in the United States
Herbenick D, et al.
Condom use during most recent vaginal intercourse event among a probability sample of adults in the United States
Sanders SA, et al.

A workshop entitled Beyond 2010: Gaps, Challenges, and Priorities for the Future of Preclinical HIV Pre-Exposure Prophylaxis (PrEP) was sponsored by the Division of AIDS (DAIDS) of the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), on October 20-21, 2009, in Bethesda, Maryland. The objective of the workshop was to identify the main gaps in current knowledge, challenges, and priorities for the establishment of a PrEP preclinical pipeline and to also provide guidance for future directions of the field and DAIDS activities in this area. This 2-day workshop, through various presentations and breakout group discussions, specifically addressed four main topics that will be critical in identifying and advancing the next generation of PrEP candidates for clinical testing. The topics were (1) drug discovery, (2) pharmacokinetics (PK) and pharmacodynamics (PD), (3) animal models, and (4) delivery systems for prolonged activity. We report here a summary of the presentations and highlights of salient discussion topics from this workshop.

Antibody 2G12 uniquely neutralizes a broad range of HIV-1 isolates by binding the high-mannose glycans on the HIV-1 surface glycoprotein, gp120. Antigens that resemble these natural epitopes of 2G12 would be highly desirable components for an HIV-1 vaccine. However, host-produced (self)-carbohydrate motifs have been unsuccessful so far at eliciting 2G12-like antibodies that cross-react with gp120. Based on the surprising observation that 2G12 binds nonproteinaceous monosaccharide D-fructose with higher affinity than D-mannose, we show here that a designed set of nonself, synthetic monosaccharides are potent antigens. When introduced to the terminus of the D1 arm of protein glycans recognized by 2G12, their antigenicity is significantly enhanced. Logical variation of these unnatural sugars pinpointed key modifications, and the molecular basis of this increased antigenicity was elucidated using high-resolution crystallographic analyses. Virus-like particle protein conjugates containing such nonself glycans are bound more tightly by 2G12. As immunogens they elicit higher titers of antibodies than those immunogenic conjugates containing the self D1 glycan motif. These antibodies generated from nonself immunogens also cross-react with this self motif, which is found in the glycan shield, when it is presented in a range of different conjugates and glycans. However, these antibodies did not bind this glycan motif when present on gp120.

Objective To examine the frequency of three sexual behaviours from the most active to the least active members of the population in various subpopulations using measures of inequality.

Methods Data from a US national probability sample of the population aged 15-44 years (National Survey of Family Growth) were used. Gini coefficients and Lorenz curves were calculated in order to examine the concentration of three sexual behaviours: vaginal sex acts (past 4 weeks) and number of opposite-sex partners (past 12 months; lifetime). Analyses were conducted separately for men and women and subpopulations of interest (by age, race/ethnicity, educational level and poverty level).

Results The sexual behaviours examined were concentrated within the most active members of the population. This concentration was most pronounced for vaginal sex acts in the past 4 weeks and lifetime opposite-sex partners, with the top 5% of each population accounting for more of the sexual behaviour than the bottom 50% of the population. Sexual behaviours were most concentrated among adolescents, the least educated and the most impoverished. Some subpopulations had similar mean or median numbers of sex acts (or sex partners), but had different degrees of concentration of these behaviours. Finally, the most impoverished men and women had the highest concentration levels for two of the three sexual behaviours (vaginal sex acts, opposite-sex partners in past 12 months).

Conclusion Given that sexual behaviours tended to be highly concentrated in subpopulations that are often at the highest risk of sexually transmitted infections, targeted interventions may be the most efficient method to reduce risk in these groups while minimising potential unintended consequences.

The New Zealand white rabbit model (Oryctolagus cuniculus) is widely used to test whether HIV vaccine candidates elicit systemic antibody responses; however, its use in mucosal immunology has not been fully exploited due to the difficulty in collecting mucosal specimens longitudinally and reproducibly. Here we describe feasible and non-feasible methods to collect vaginal and nasal specimens from nulliparous rabbits. Non-feasible methods were those resulting in poor reproducibility and considerable animal twitching during sampling, whereas feasible methods resulted in no animal twitching and potential for sampling reproducibility. Standard operating procedures (SOPs) were implemented to collect vaginal swabs yielding total IgA titres ranging from 12,500 to 312,500. Intranasal immunisation with a naked DNA vaccine encoding HIV gp140 elicited HIV envelope-specific IgA detectable in nasal but not in vaginal secretions. Our methods provide an alternative to reliably assess pre- and post-vaccination mucosal antibody titres longitudinally in rabbits as part of mucosal HIV vaccine immunogenicity studies.

The Global Health Council is pleased to invite you to join us for the Third Annual Beth Waters Memorial Lecture:

The Road to Developing an AIDS Vaccine: Lessons Learned in Research and Advocacy
Tuesday, October 12, 2010, 10 am-Noon
Newseum, Room 705-706, 605 Pennsylvania Avenue, NW, Washington, D.C.
Featured Speaker Mitchell Warren, Executive Director, AVAC

Beth Waters, a health care public relations specialist who passed away in 2006, had a great passion for vaccine advocacy to prevent and treat diseases worldwide. In commemoration of her crusading spirit, the Global Health Council is pleased to present the third annual Beth Waters Memorial Lecture. Vaccines are one of the world's most effective public health tools. This lecture will highlight the road to accelerating the ethical development of AIDS vaccines through progress in research, policy analysis, advocacy and community mobilization. Key scientific, policy, social, ethical and economic challenges in vaccine development will also be discussed.

Sydney will host back-to-back sexual health and HIV conferences this month. The Australasian Sexual Health Conference runs from October 18 to 20, followed by the Australasian HIV/AIDS Conference 2010 from October 20 to 22. Both gatherings will be held at the Sydney Convention and Exhibition Centre in Darling Harbour. At the sexual health conference, topics will include the nature of human desire, and STI prevention strategies amongst adolescents. There will also be symposia on chlamydia, sexual assault, the sex industry, and sexual dysfunction. The HIV/AIDS conference will include a gay men's HIV prevention satellite event titled 'Epidemic to Endemic'. This will be held at the Powerhouse Museum on October 19, and will bring together researchers, advocates, educators and policy makers to discuss HIV prevention in gay men.

For more information, visit www.hivaidsconference.com.au and www.sexualhealthconference.com.au.

The National Institute of Allergy and Infectious Diseases of the National Institutes of Health recently awarded a $7.8 million grant to the International AIDS Vaccine Initiative to research the generation of neutralizing antibodies developed by individuals with HIV. Investigators, led by IAVI's Pascal Poignard, will investigate why these antibodies develop within certain people but not others, and what factors may contribute to their emergence, according to GenEngNews.com.

Researchers from the NIH and IAVI recently discovered several particularly effective antibodies against HIV. These antibodies are able to bind with and disable a broad range of HIV variants, and are thought to have potential in the creation of an effective vaccine for AIDS. Studies have suggested that anywhere from 10 to 20 percent of HIV positive individuals develop broadly neutralizing responses, usually three to four years after infection. It is unknown why this happens.

The MSMGF is very happy to announce that video recordings are now available from each of the plenary speeches from the BE HEARD MSM Pre-Conference at the 2010 International AIDS Conference in Vienna. The plenary sessions featured a number of powerful presentations from key global leaders addressing the current state of health and human rights of men who have sex with men worldwide.  Since the event, we have had numerous requests for recordings of these presentations from conference participants as well as those who could not attend.  The speeches are quite thought-provoking and many can act as useful tools for future advocacy purposes. All videos are currently available on the MSMGF's YouTube Channel.

Solicitation Number NIAID-DMID-NIHAI201010

Response Date Jan 14, 2011 3:00 pm Eastern

Introduction The National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), of the Department of Health and Human Services (DHHS) supports research related to the basic understanding of microbiology and immunology leading to the development of vaccines, therapeutics, and medical diagnostics for the prevention, treatment, and diagnosis of infectious and immune-mediated diseases. The NIAID, Division of Microbiology and Infectious Diseases, has an interest in identifying innovative approaches to effectively treat viral infections.

Description The primary objective of this solicitation is to support clinical trials and clinical studies to further the development of therapies for select rare and emerging viral diseases. This solicitation targets the evaluation of new or existing therapies (alone or in combination) in a variety of underserved or special patient populations (e.g., immunosuppressed patients (non-HIV); pediatric patients, elderly patients). Because many of the targeted diseases may not be clinically well characterized, appropriate natural history studies may be necessary. When appropriate, the use of innovative or adaptive clinical trial designs, particularly in cases where the disease incidence is rare or the patient population presents unique challenges, is encouraged.