24 SEPTEMBER 2010, VOLUME 11, ISSUE 35

Last week, the US Senate voted against a bill that would have made the manufacturing R&D tax credit introduced in 1981 to boost industrial innovation a permanent fixture of the US budget. Democrats in the chamber rejected the proposal on concerns that last minute Republican efforts to attach it to a small business stimuli plan would delay the latter scheme's progress ahead of November 2 elections. So, while the small business bill was subsequently approved, the political manoeuvring that accompanied its passage means that, for the time being at least, R&D focused manufacturers lack clarity on tax provision. This uncertainty could end up hurting the US pharmaceutical industry and chemical firms that supply it according to Society of Chemical Manufacturers and Affiliates (SOCMA) CEO Lawrence Sloan.

The HIV/AIDS pandemic continues to spread and an AIDS vaccine is urgently needed.
Regional alliances and international collaborations can foster the development and evaluation of the next generation of AIDS vaccine candidates. The importance of coordinating and harmonizing efforts across regional alliances has become abundantly clear. We recently formed the AIDS Vaccine for Asia Network (AVAN) to help facilitate the development of a regional AIDS vaccine strategy that accelerates research and development of an AIDS vaccine through government advocacy, improved coordination, and harmonization of research; develops clinical trial and manufacturing capacity; supports ethical and regulatory frameworks; and ensures community participation.

Australia is rightly proud of its response to HIV. Thanks to superb formulation of public policy in the early days of the epidemic, it is not only a low-prevalence country but an international leader in many aspects of its clinical and public health responses. To maintain this fine record, Australia should change policy so that infant male circumcision rates are boosted in the face of rising heterosexual transmission of HIV.

Johnson & Johnson said Friday it is in advanced talks to acquire Dutch biotech company Crucell NV for euro1.75 billion ($2.29 billion), a deal that would boost the American health care product maker's vaccine business. In a joint statement, the companies said Johnson & Johnson, which already owns a 17.9 percent stake in Crucell, intends to offer euro24.75 per share in cash for the remainder - a 58 percent premium to Crucell's closing price Thursday of euro15.70. Shares in Crucell, whose board will recommend the offer to stockholders, jumped 56 percent to euro24.41 in Amsterdam. "The companies expect that Crucell's strength in the manufacture, discovery and commercialization of vaccines would create a strong platform for Johnson & Johnson in the vaccine market," the companies said.

Johnson & Johnson, headquartered in New Brunswick, N.J., has about $64 billion in annual sales and is the world's biggest and most broadly based health care company, with products ranging from Band-Aids and baby shampoo to contact lenses and contraceptives... Crucell's biggest-selling vaccine is Quinvaxem, which protects against five childhood diseases. But it has a number of interesting vaccines and treatments under development. Last year it was awarded a $69 million U.S. government grant for developing a universal treatment for the flu, including strains resistant to Tamiflu - the medicine most commonly used to slow influenza infections. Crucell, based in Leiden, Netherlands, is also working on a treatment for people infected with rabies and an HIV vaccine.

Significant strides have been made in the global fight against HIV, but major gaps remain that could prevent many countries from achieving UN Millennium Development Goal (MDG) six relating to HIV/AIDS, malaria and other diseases. IRIN/PlusNews examines global efforts to halt and begin to reverse the spread of HIV/AIDS.

Access to treatment - More than five million people currently have access to life-prolonging antiretroviral drugs, a 12-fold increase over the past six years. However, this still represents just one third of people who need HIV treatment. In 2008, 38 percent of the 730,000 children estimated to need antiretrovirals (ARVs) in low- and middle-income countries had access to them. UNAIDS is calling for the implementation of a new treatment approach called "Treatment 2.0", to drastically scale up testing and treatment; it estimates that successful implementation of "Treatment 2.0" could avert 10 million deaths by 2025, and reduce new infections by a third.

New infections - Twenty-two of the worst affected countries in sub-Saharan Africa have reduced HIV incidence by more than 25 percent in the last eight years, according to UNAIDS. Some of the best performers in reducing new infections are Ethiopia, Nigeria, Zambia and Zimbabwe; HIV incidence is on the rise in Uganda, once a leader in the fight against HIV.

Recent preliminary results of the microbicide gel, Tenofovir, which showed that it can protect women from HIV infection by about 39%, have sparked concern that people might be less cautious about the use of condoms. Communities say condoms are already being used sparingly.

The announcement of the much-awaited Caprisa results in July has elicited a mixed reaction among communities, with some suggesting that it might worsen the rate of condom use. Vusi Msiza, from Kwa-Tema, on Gauteng's East Rand, said that the results have brought hope, but cautioned that they could also create a misperception. "It is good that we had this study, but I am also scared that people will stop using condoms and there might be issues of new infections if we don't do well in terms of messaging the whole thing. We need to advocate, so we are clear. I also want to challenge men to take initiative... let us men take initiative of saying we need to use condoms and supporting our women", Msiza said.

A woman who is part of an HIV/AIDS community support group in Benoni, also on Gauteng's East Rand, agrees that the tenofovir gel may signal an incorrect message. The woman, who wanted to remain anonymous and lives in an informal settlement, expressed her concern in some women not being given a choice by their men to use protection. "Some are not allowed to even use those condoms. If they do, then they get hit or don't get money to buy food in the house. One woman told me that as it is now, her man was not here for a whole week. He was not sleeping at home, but when he came back he just wanted to have sex and didn't want me to ask questions on where he was from or that we should use condoms. He just wanted it like that and I had to give him. He is the breadwinner in the house; otherwise her and her children won't get food. So, I hope that this gel doesn't discourage people from using condoms", she said.

Countries in Sub-Saharan Africa are leading a global decline in new HIV infections, the UN has said. UNAids said 22 countries in the world's worst affected region had seen a drop in new cases of more than 25%. The fall was because of greater awareness and better use of preventative measures, it said. But UNAids also noted that cases of HIV were increasing in Eastern Europe and Central Asia, and among gay men in developed countries.

Michel Sidibe, UNAids executive director, said the world was making "real progress" towards achieving the sixth Millennium Development Goal (MDG6) of halting and reversing the spread of HIV/Aids by 2015. "For the first time change is happening at the heart of the epidemic. In places where HIV was stealing away dreams, we now have hope," he said.

UNAids says there are now 5.2 million people worldwide receiving treatment for HIV/Aids, which has helped to ensure that 200,000 fewer people died from the virus in 2008 than in 2004. The agency said young people "are leading the prevention revolution by choosing to have sex later, having fewer multiple partners and using condoms, resulting in significantly fewer new HIV infections in many countries highly affected by Aids". The use of male condoms has also doubled in the past five years, while the report notes that "tradition is giving space to pragmatism" in many communities as they embrace male circumcision, which research shows has the potential to reduce HIV infections among men by nearly 60%.

With help from $3.8 million in new funding, Nebraska researchers are working on production of a cream that would help women resist transmission of HIV, the AIDS virus. The money for the work at the University of Nebraska-Lincoln's Biological Process Development Facility comes from the Mintaka Foundation of Medical Research, which is supported by the Wellcome Trust. The UNL researchers are developing a process to manufacture a stable and affordable microbicide called 5P12-RANTES.

See UNL press release for more information. 

Borrowing a concept used to make breath strips, researchers at the University of Pittsburgh are developing a quick-dissolving vaginal film containing an HIV-blocking drug, officials said Wednesday. "The idea is that it would dissolve quickly in the vagina to prevent HIV infection," said Sharon Hillier, a senior investigator at Magee-Womens Research Institute and co-principal investigator of the project. "It's a bit of an old technique, like the Listerine breath mint strip, but it's a whole new way of delivering the drug potentially in a less expensive way."

An $11.8 million, five-year federal grant from the National Institute of Allergy and Infectious Diseases is paying for the work, led also by Lisa Cencia Rohan, an associate professor at Pitt's School of Pharmacy. Researchers plan to conduct tests within a year on about 40 local, healthy women. The film would contain a version of the anti-viral drug tenofovir, which is known to reduce the risk of HIV transmission and is used to treat HIV. It comes in a gel touted in a recent South African study, which found that women who used it before and after sex were 39 percent less likely to become infected with the virus.

Despite the gel's promise, health advocates fear lack of money could derail plans to make it available for general use. About $42 million is needed to carry out research to establish whether the gel is effective in different populations of women, according to UNAIDS, the United Nations AIDS agency.

In a discovery that sheds new light on the history of AIDS, scientists have found evidence that the ancestor to the virus that causes the disease has been in monkeys and apes for at least 32,000 years -- not just a few hundred years, as had been previously thought. That means humans have presumably been exposed many times to S.I.V., the simian immunodeficiency virus, because people have been hunting monkeys for millenniums, risking infection every time they butcher one for food. And that assumption in turn complicates a question that has bedeviled AIDS scientists for years: What happened in Africa in the early 20th century that let a mild monkey disease move into humans, mutate to become highly transmissible and then explode into one of history's great killers, one that has claimed 25 million lives so far?

Home-based voluntary counselling and testing (HCT) can help to diagnose HIV early among high-risk children, new research in western Kenya has found. "Through home-based counselling and testing, you are able to get children and parents who might not go to health facilities for these services," said Samson Ndege, one of the authors of the study and HCT project coordinator with the USAID-supported Academic Model Providing Access to Healthcare (AMPATH), which cares for more than 100,000 HIV-positive adults and children in the region. "HCT provides an opportunity to... link children and parents to treatment." The study, published in the Journal of Acquired Immune Deficiency Syndromes, looked at the uptake of HIV testing and HIV prevalence among children given HCT and aged between 18 months and 13 years, whose mothers were either dead, HIV-infected or of unknown HIV status.

To read the abstract of the study in JAIDS, see "Acceptance of HIV testing for children ages 18 months to 13 years identified through voluntary, home-based HIV counseling and testing in Western Kenya" in the "Published Research" section of this issue of the NewsDigest.

At this summer's International AIDS Conference in Vienna, two South African researchers revealed the results of an HIV prevention clinical trial that could herald a new era of HIV prevention efforts worldwide and raise a host of ethical questions regarding resource allocation, health care costs, and preventative medicine. The trial, CAPRISA 004, was the first completed trial to assess the use of an HIV antiretroviral drug as pre-exposure prophylaxis for HIV transmission. The trial investigated whether the antiretroviral drug tenofovir, in the form of a vaginal gel, could protect HIV-negative women from becoming HIV-positive.

The premise of pre-exposure prophylaxis, generally referred to as PrEP, was developed in part from the success of tenofovir and similar antiretroviral drugs at disrupting the life cycle of the human immunodeficiency virus in HIV-positive individuals. Scientists who have developed pre-exposure prophylaxis trials have hypothesized that if a drug such as tenofovir were in the blood stream or genital tract upon exposure to HIV, the virus might be destroyed before it could infiltrate host cells. Thus, an individual exposed to the virus would be protected from becoming HIV-positive.

During the past decades women have been at a higher risk of HIV infection than men. In the past, women never wore condoms during sexual intercourse. Today, high-level sensitization from health experts, government and private health institutions has increased awareness on the use of female condoms.

For women to protect themselves from HIV infection, they must not only rely on their own skills, attitudes, and behaviour regarding condom use, but also on their ability to convince their partner to use a condom. Problems related to gender, culture and power have been barriers to maintaining safer sex practices with a primary partner for most women, especially those living in rural areas. It is important to understand here that HIV prevention strategies must target both women and men in heterosexual relationships, and address gender norms in sexual decision making.

In most African traditions, women were disproportionately represented among the poor. Because of this, women were less likely to have health insurance and access to healthcare services. Nevertheless, today a small proportion of women living in poverty are also disproportionately affected by HIV. For these women, the struggle for daily survival may take precedence over concerns about HIV infection, whose impact may not be seen for several years. Like many in committed relationships, women may find intimacy in their relationship to be more important than protection against HIV. Unsafe sex may be linked to emotional and social insecurity among women that are not necessarily financial dependent on men.

Malawi will not officially promote male circumcision as an HIV-prevention strategy, two officials said Wednesday, citing a lack of evidence to support the practice. "We have no scientific evidence that circumcision is a sure way of slowing down the spread of AIDS," said Dr. Mary Shaba, a top HIV/AIDS official in Malawi. Shaba said she had seen studies that showed a comparatively low rate of HIV/AIDS in countries where circumcision is encouraged or mandated. But she said she believed circumcision may not be the only reason for this.

Chairman of the National AIDS Commission and Anglican Bishop Emeritus Bernard Malango said studies in Malawi raised doubts about the effectiveness of circumcision in preventing HIV. "If you go to areas where circumcision is practiced, you still find a good number of people that are HIV-positive," he said.

The U.N. said last year that studies show universal male circumcision in sub-Saharan Africa could prevent 5.7 million new infections and 3 million deaths over 20 years. Circumcision is common among Muslims and some tribes in Malawi, but is not universally practiced. But since reports emerged that circumcision may slow the spread of HIV, an increasing number of men have flocked to hospitals for the procedure.

According to information in the Swaziland Demographic and Health Survey, the numbers of men who are circumcised are more likely to be carriers of the HIV virus. The survey contains information from the year 2006 and it summarizes the findings of the survey conducted by the Swaziland Central Statistical Office (SCO).

According to the report, 22% of men who are circumcised were the carriers of the virus as compared to 20% in uncircumcised men. The acronym HIV stands for Human Immuno Deficiency. The report further provides information that circumcised men are less likely to contract the virus due to the physiological difference between circumcised and uncircumcised men after the procedure. However, the data carried by the report is a witness to altogether another scenario. The report also states that the function of male circumcision to protect a man from HIV can be of full use only after the full removal of the foreskin and not the partial removal, as partial removal will only provide partial protection from the virus.

Many women in Tanzania are unable to access female condoms five years after the product was introduced with objective to prevent Sexually Transmitted Infections (STI), including HIV/AIDS and unplanned pregnancies. One of the female condom varieties, 'Lady Pepeta' is a soft yet strong, polyurethane sheath with a plastic ring at a closed end to keep it fixed within the female organ during sexual intercourse. The larger ring at the opening stays outside, spreading over a woman's external genitalia.

After its launch as the female-controlled shield against HIV, the female condom is still largely marginalised and inaccessible. A random survey by the 'Sunday News' in several pharmacies in Dar es Salaam city centre revealed that female condoms are not easily available. On the contrary, male condoms enjoy wider promotion. This phenomenon poses particular problems in the context of the HIV and AIDS pandemic, which is increasingly characterised by unfair deal on women and girls. Female condoms are aimed at ensuring a woman-controlled sex. The condom provides a shield against both pregnancy and STIs, including HIV infections.

The global fight against HIV/AIDS has found a powerful if unfashionable ally in male circumcision. Research into the spread of the virus in Africa has revealed a reduced rate of transmission in those regions where male circumcision is the norm. The practise rooted in religion and culture was increasingly seen as a "surgical vaccine" against HIV and must be part of efforts to curb the virus' spread, says harm minimisation advocate Dr Alex Wodak in a co-authored paper.

"A wealth of research has shown that the foreskin is the entry point that allows HIV to infect men during intercourse with an infected female partner," Dr Wodak said. "Soon after the HIV pandemic was first recognised, much lower HIV prevalence was found in areas of sub-Saharan Africa, where more than 80 per cent of males had been circumcised than in areas where the circumcision rate was less than 20 per cent." "Circumcision of males is now referred to by many as surgical vaccine against a wide variety of infections and adverse medical conditions over the lifetime."

In 2009, Reuben Granich and colleagues reported, on the basis of a modelling study, that HIV could be eliminated in South Africa by use of a universal "test and treat" strategy. The strategy involved annual testing of all 32 million adults; immediate antiretroviral therapy for those who test positive, irrespective of their CD4+ cell count or stage of infection; and a package of prevention interventions (male circumcision, behaviour change programmes, condom promotion, and treatment of curable sexually transmitted infections) extensive enough to cause a 40% reduction in incidence (the proportion stated as necessary for elimination by WHO). The utility, feasibility, and potential effectiveness of this strategy have been extensively discussed. However, little attention has been paid to Granich and colleagues' estimates of the cost of the proposed strategy, and whether these estimates include all costs or just the cost of treatment.

The number of adults that would be on treatment in South Africa if this proposed strategy is enacted is shown in figure A. Notably, 6 years after the strategy is implemented, about 4.3 million adults would be on treatment. Additionally, about 2.3 million individuals in South Africa would be on treatment when the WHO elimination threshold (ie, one new HIV infection per 1000 adults) is reached. Clearly, the strategy would be extremely costly in terms of treatment alone, but it would also require substantial financial resources to pay for the extensive prevention interventions, as well as for annual testing. Most importantly, a huge and immediate financial investment would be necessary to scale up the health-care infrastructure by about ten-fold to treat and monitor more than 4 million adults every year (currently 500 000 are treated annually).

Commentary
In sub-Saharan Africa, the burden of HIV infection falls largely on women, who represent about 60% of all people living with the infection in the region.1 Young women are at particular risk; in some areas the prevalence of infection in women aged 15-24 years is nearly three times that of young men. This heightened vulnerability is driven by social, economic, and cultural factors that include transactional partnerships with older men, who are more likely to be infected. In gender-inequitable and transactional sexual relationships, decisions about behavioural change and condom use are mainly controlled by men and thus, prevention approaches have not greatly reduced the risk of HIV infection for young women in sub-Saharan Africa. Substantial research investment has gone into finding an effective prevention technology for women.

In The Lancet today, Sheena McCormack and colleagues describe a large randomised trial of PRO2000 vaginal gel for the prevention of HIV-1 infection in women. The investigators found that 0.5% and 2% PRO2000 gels provided no protection against HIV infection. This finding is disappointing in view of the promising results from the HPTN 035 trial of PRO2000 that found a non-significant 30% reduction in HIV-1 incidence compared with placebo gel in the intention-to-treat analysis. Despite the success of the trial in terms of the investigators' commitment to community partnerships, their incorporation of mixed methods, and their adherence to the highest international scientific standards, McCormack and colleagues' results will certainly indicate the end of the road for PRO2000 as a potential HIV-prevention tool for women.

However, today's paper follows on the heels of the much anticipated results of the CAPRISA 004 trial, which were released in July at the XVIII International AIDS Conference. Investigators found that a microbicide containing 1% tenofovir reduced a woman's risk of HIV infection by 39%. Furthermore, the protective effect of the gel increased with consistency of use; women who used the gel in more than 80% of sex acts had a 54% reduction in HIV infections. After nearly two decades of microbicide research, in which all of the 11 randomised trials of candidate microbicides failed to show any protective effect and some microbicides might have actually increased risk, the CAPRISA results are a substantial breakthrough for HIV prevention. Ongoing and future studies (such as the VOICE study [MTN-003]), which address the relative value, methods of delivery, and regimens for oral versus topical pre-exposure prophylaxis, will verify whether this microbicide could alter the course of the epidemic.

To read the abstract of the paper mentioned in this article, see below, "PRO2000 vaginal gel for prevention of HIV-1 infection (Microbicides Development Programme 301): a phase 3, randomised, double-blind, parallel-group trial".

Background Innovative prevention strategies for HIV-1 transmission are urgently needed. PRO2000 vaginal gel was efficacious against HIV-1 transmission in studies in macaques; we aimed to assess efficacy and safety of 2% and 0.5% PRO2000 gels against vaginal HIV-1 transmission in women in sub-Saharan Africa.

Methods Microbicides Development Programme 301 was a phase 3, randomised, double-blind, parallel-group trial, undertaken at 13 clinics in South Africa, Tanzania, Uganda, and Zambia. We randomly assigned sexually active women, aged 18 years or older (>=16 years in Tanzania and Uganda) without HIV-1 infection in a 1:1:1 ratio to 2% PRO2000, 0.5% PRO2000, or placebo gel groups for 52 weeks (up to 104 weeks in Uganda). Randomisation was done by computerised random number generator. Investigators and participants were masked to group assignment. The primary efficacy outcome was incidence of HIV-1 infection before week 52, which was censored for pregnancy and excluded participants without HIV-1 follow-up data or with HIV-1 infection at enrolment. HIV-1 status was established by rapid tests or ELISA at screening at 12 weeks, 24 weeks, 40 weeks, and 52 weeks, and confirmed in a central reference laboratory. The primary safety endpoint was an adverse event of grade 3 or worse. Use of 2% PRO2000 gel was discontinued on Feb 14, 2008, on the recommendation of the Independent Data Monitoring Committee because of low probability of benefit. This trial is registered at http://isrctn.org/, number ISRCTN 64716212.

Findings We enrolled 9385 of 15 818 women screened. 2591 (95%) of 2734 participants enrolled to the 2% PRO2000 group, 3156 (95%) of 3326 in the 0.5% PRO2000 group, and 3112 (94%) of 3325 in the placebo group were included in the primary efficacy analysis. Mean reported gel use at last sex act was 89% (95% CI 86-91). HIV-1 incidence was much the same between groups at study end (incidence per 100 woman-years was 4.5 [95% CI 3.8-5.4] for 0.5% PRO2000 vs 4.3 [3.6-5.2] for placebo, hazard ratio 1.05 [0.82-1.34], p=0.71), and at discontinuation (4.7 [3.8-5.8] for 2% PRO2000 gel, 3.9 [3.0-4.9] for 0.5% PRO2000 gel, and 3.9 [3.1-5.0] for placebo gel). Incidence of the primary safety endpoint at study end was 4.6 per 100 woman-years (95% CI 3.9-5.4) in the 0.5% PRO2000 group and 3.9 (3.2-4.6) in the placebo group; and was 4.5 (3.7-5.5) in the 2% PRO2000 group at discontinuation.

Interpretation Although safe, 0.5% PRO2000 and 2% PRO2000 are not efficacious against vaginal HIV-1 transmission and are not indicated for this use.

Background Human immunodeficiency virus type 1 (HIV-1)-infected men are at increased risk for anal cancer. Human papillomavirus (HPV) vaccination may prevent anal cancer caused by vaccine types.

Methods AIDS Malignancy Consortium Protocol 052 is a single-arm, open-label, multicenter clinical trial to assess the safety and immunogenicity of the quadrivalent HPV (types 6, 11, 16, and 18) vaccine in HIV-1-infected men. Men with high-grade anal intraepithelial neoplasia or anal cancer by history or by screening cytology or histology were excluded. Men received 0.5 mL intramuscularly at entry, week 8, and week 24. The primary end points were seroconversion to vaccine types at week 28, in men who were seronegative and without anal infection with the relevant HPV type at entry, and grade 3 or higher adverse events related to vaccination.

Results There were no grade 3 or greater adverse events attributable to vaccination among the 109 men who received at least 1 vaccine dose. Seroconversion was observed for all 4 types: type 6 (59 [98%] of 60), type 11 (67 [99%] of 68), type 16 (62 [100%] of 62), and type 18 (74 [95%] of 78). No adverse effects on CD4 counts and plasma HIV-1 RNA levels were observed.

Conclusions The quadrivalent HPV vaccine appears safe and highly immunogenic in HIV-1-infected men. Efficacy studies in HIV-1-infected men are warranted.

Dapivirine, a nonnucleoside reverse transcriptase inhibitor, is in development as a microbicide for the protection of women against HIV infection. A randomized, double-blind, phase 1 trial was conducted in 36 healthy HIV-negative women to compare the pharmacokinetics of 2 dapivirine vaginal gel formulations (0.05% each) and their safety with the hydroxyethyl cellulose-based universal placebo gel. Gel was self-administered once daily for a total of 11 days. Blood and vaginal fluid samples were collected sequentially over 24 days for pharmacokinetic analysis. Safety was evaluated by pelvic examination, colposcopy, adverse events, and clinical laboratory assessments. Adverse event profiles were similar for the 3 gels. Most events were mild and not related to study gel. Headache and vaginal hemorrhage (any vaginal bleeding) were most common. Plasma concentrations of dapivirine did not exceed 1.1 ng/mL. Steady-state conditions were reached within approximately 10 days. Dapivirine concentrations in vaginal fluids were slightly higher for Gel 4789, but Cmax values on days 1 and 14 were not significantly different. Terminal half-life was 72-73 hours in plasma and 15-17 hours in vaginal fluids. Both formulations of dapivirine gel were safe and well tolerated. Dapivirine was delivered to the lower genital tract at concentrations at least 5 logs greater than in vitro inhibitory concentrations.

Editor's Note: Abstract unavailable. Article available as HTML full text and PDF with a subscription.

Background Quadrivalent human papillomavirus vaccine (QHPV) is >95% effective in preventing infection with vaccine-type human papillomavirus. The safety and immunogenicity of QHPV are unknown in HIV-infected children.

Methods HIV-infected children (N = 126) age >7 to <12 years, with a CD4% >=15 and on stable antiretroviral therapy if CD4% was <25 were blindly assigned to receive a dose of QHPV or placebo (3:1 ratio) at 0, 8, and 24 weeks. Adverse events were evaluated after each dose. Serum antibody against QHPV antigens was measured by a competitive Luminex immunoassay 1 month after the third QHPV dose.

Results The safety profile of QHPV was similar in the 2 study arms and to that previously reported for QHPV recipients. QHPV did not alter the CD4% or plasma HIV RNA. Seroconversion to all 4 antigens occurred in >96% of QHPV recipients and in no placebo recipients. Geometric mean titer was >27 to 262 times greater than the seropositivity cutoff value, depending on the antigen, but was 30%-50% lower against types 6 and 18 than those of age-similar historical controls.

Conclusions QHPV was safe and immunogenic in this cohort of HIV-infected children. Efficacy trials are warranted.

HIV integrase inhibitors based on a novel bicyclic pyrimidinone core is presented. Nine variations of the core scaffold are evaluated leading to optimization of the 6:6 core giving compound 48 with an EC50 of 3 nM against wild type HIV infected T-cells.

See related article: Giang Le NV, et al. Design of a series of bicyclic HIV-1 integrase inhibitors. Part 2: Azoles: Effective metal chelators. Bioorganic & Medicinal Chemistry Letters. 1 October 2010; 20(19):5909-5912.

Purpose Develop a preclinical in vitro algorithm enabling de novo design of semisolid vaginal drug delivery gels, by using biomechanical modeling of gel spreading in the vaginal canal and empirically relating gel composition to mechanical properties and predicted performance.

Methods Gel performance was defined through a multivariate objective function constructed from gels' mechanical properties and selected performance criteria for gel spreading within the vaginal canal. Mixture design of experiment was used to establish a semi-empirical relationship linking composition-property and property-performance relationships for gels with varying concentrations of hydroxyethylcellulose and Carbopol 974P. This permits definition of a local optimum for gel composition and volume of administration, within a defined gel composition space.

Results Rheological behavior and, consequently, the value of the objective function varied broadly with composition. The algorithm indicated a 3.0 wt% HEC gel as the near optimal composition for a 3.5 mL applied volume for gels designed to spread throughout the vagina.

Conclusions The algorithm introduced herein is a novel tool that facilitates an understanding of the composition-property-performance relationship for vaginal semisolid drug delivery gels. This approach has promise as a scientific methodology for evaluation and optimization of vaginal gels prior to in vivo investigations.

Background Home-based voluntary counseling and testing (HCT) presents a novel approach to early diagnosis. We sought to describe uptake of pediatric HIV testing, associated factors, and HIV prevalence among children offered HCT in Kenya.

Methods The USAID-Academic Model Providing Access to Healthcare Partnership conducted HCT in western Kenya in 2008. Children 18 months to 13 years were offered HCT if their mother was known to be dead, her living status was unknown, mother was HIV infected, or of unknown HIV status. This retrospective analysis describes the cohort of children encountered and tested.

Results HCT was offered to 2289 children and accepted for 1294 (57%). Children were more likely to be tested if more information was available about a suspected or confirmed maternal HIV infection [for HIV-infected living mothers] odds ratio (OR) = 3.20, 95% confidence interval (CI): 1.64 to 6.23), if parents were not in household (OR = 1.50, 95% CI: 1.40 to 1.63), if they were grandchildren of head of household (OR = 4.02, 95% CI: 3.06 to 5.28), or if their father was not in household (OR = 1.41, 95% CI: 1.24 to 1.56). Of the eligible children tested, 60 (4.6%) were HIV infected.

Conclusions HCT provides an opportunity to identify HIV among high-risk children; however, acceptance of HCT for children was limited. Further investigation is needed to identify and overcome barriers to testing uptake.

Purpose of review Results of trials determining if pre-exposure prophylaxis (PrEP) with antiretroviral drugs prevents transmission of HIV are expected soon. Tenofovir and emtricitabine - currently evaluated as PrEP - are popular in treatment of HIV. Drug resistance could, therefore, be critical in the use of PrEP. We review the literature regarding risks associated with drug resistance owing to PrEP.

Recent findings Few studies addressed the issue of drug resistance to tenofovir and/or emtricitabine. Studies in HIV-1-infected individuals followed small numbers of patients for a short time. Studies in macaques were well designed, but used SHIV, which has an attenuated course of infection. The available information suggests that the probability of emergence of drug resistance is small. Infections that occurred despite use of PrEP had reduced peak viremia, which could reduce HIV transmissibility. Mathematical modeling suggests that, although transmitted drug resistance may under some circumstances increase, the benefits of PrEP outweigh the risks associated with resistance.

Summary Tenofovir and emtricitabine are recommended in first-line treatment. The potentially limited impact of drug resistance should, therefore, be confirmed in daily practice. Surveillance of drug resistance is recommended in areas where PrEP is used. Patients that became infected despite use of PrEP should be closely monitored for virological failure.

Meeting Dates: 15-16 November 2010
Venue: The Royal Society, London
Organised by Professor Adrian Hill and Professor Brian Greenwood FRS

Recent advances in knowledge of pathogen genomics and of innate immunity provide exceptional opportunities for the development of new vaccines. Development of effective vaccines against some major killers such as HIV, malaria and tuberculosis has proved challenging but progress is being made and many new vaccines have reached the stage of clinical trials. Development of vaccines against some non-infectious diseases is also making progress. This meeting will review opportunities to design, develop and deploy the new vaccines urgently needed to meet global health priorities.

Speakers include: Professor Shizuo Akira, Dr Martin Bachmann, Dr Rana Hajjeh, Professor Adrian Hill, Professor Keith Klugman, Professor Margaret Liu, Dr Julian Lob-Levyt, Dr Gary Nabel, Sir Gustav Nossal FRS, Professor Albert Osterhaus, Professor David Paton, Dr Rino Rappuoli and Dr Jerald Sadoff.

Chairs include: Professor Brian Greenwood FRS, Dr Marie-Paule Kieny, Professor Richard Moxon FRS.

Enhance your advocacy skills and bone up on some of the basics. On Wednesday, September 29, Jim Turpin of the Microbicide Research Branch at the National Institutes of Health, National Institutes of Allergy and Infectious Diseases, will explain the basic science of drug discovery - the research that happens before we move on to Phase I safety testing in people. Many of us find basic science confusing, daunting, and scary. Jim will show us that it doesn't have to be any of those things, and is in fact, fascinating!

Teleconference: The Basics of Drug Development Science-Nothing to be scared of!
Wednesday, September 29, 2010
10am Eastern Standard Time (EST)
Register at the following link: http://www.facebook.com/l/5fb3dJHCGevZDF2wFHuxjbsldyg;https://cc.readytalk.com/cc/schedule/display.do?udc=wygn2fou37e0

Women's Policy, Inc. (WPI) is pleased to provide information from a briefing held September 15, 2010, "Integrated Health Programs for Women and Children: Lessons from the Field." This information is available on WPI's website.

In partnership with Computer Aid International, BioMed Central will be hosting a two-day conference on open access publishing at Kenyatta University in Nairobi, Kenya, from 10-11 November 2010. Open access to the results of scientific and medical research has potential to play an important role in international development, and this conference will discuss the benefits of open access publishing in an African context, from the perspective of both readers seeking access to information, and researchers seeking to globally communicate the results of their work.

There is no cost to attend the conference, but space is limited. To reserve your place, or to sign up to receive additional information, please email: events@biomedcentral.com.

The Global Health Technologies Coalition (GHTC) has authored a new fact sheet on the FDA's role in global health. The fact sheet explores the crucial role of the agency in ensuring the safety of health tools that work to prevent, diagnose, and treat infectious diseases that affect millions of people worldwide. The fact sheet is available at the following link: http://www.ghtcoalition.org/files/FDAfactsheet.pdf.

Many post conference resources are now available on the AIDS 2010 website. Whether you were able to join us in person in Vienna or not, you will find a wealth of information at your fingertips, including access to the latest developments in HIV-related programming, policy and scientific research. 

University of Miami President Donna E. Shalala has been awarded the 2010 Nelson Mandela Award for Health and Human Rights. Shalala, who served as U.S. Secretary for Health and Human Services in the Clinton administration, received the award on Thursday, September 16 at a ceremony and dinner at Blair House hosted by the current U.S. Secretary for Health and Human Services, Kathleen Sebelius, and the Kaiser Family Foundation. The event honored Shalala's retirement from the foundation's Board of Trustees. The award recognizes Shalala for her dedication to advancing access to health care in the United States and for helping disadvantaged people around the world, as well as for her special commitment to ending apartheid and developing democracy in South Africa.

The Bill and Melinda Gates Foundation published their Global Health Strategy online at www.gatesfoundation.org/global-health/Documents/global-health-strategy-overview.pdf. The Strategy describes the principles, priorities, and future directions of the foundation's Global Health Program.

Inovio Pharmaceuticals, Inc., a leader in the development of therapeutic and preventive vaccines against cancers and infectious diseases, announced today the Phase I clinical study assessing Inovio's PENNVAX(TM)-B DNA vaccine delivered using its proprietary electroporation technology in a preventive setting has fully completed the enrollment of 48 healthy volunteers. The multi-center study is being conducted by Inovio's clinical collaborator, the HIV Vaccine Trials Network (HVTN), at several clinical sites under a protocol designated HVTN-080.

Inovio previously reported data from non-human primates demonstrating up to a 100-fold enhancement in immune responses resulting from the vaccine when delivered via in vivo electroporation compared to syringe injection without electroporation. This HVTN-080 study, which is assessing safety and levels of immune responses in humans, is sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), an agency of the National Institutes of Health (NIH).