The Weekly NewsDigest is a compilation of HIV prevention research media coverage and relevant science in peer-reviewed journals; material on
other reproductive health issues; and matters of policy and politics relevant to HIV prevention research, development and advocacy.
Its purpose is to raise awareness around the range of opinions and information about HIV prevention research disseminated in the press and
scientific journals and provide a neutral, objective basis for decision-making and evidence-based advocacy.
Intravenous drug users (IDUs) have been largely ignored by the government's HIV programmes on the basis that drug-taking is illegal, but a new policy is being drafted with the aim of reducing HIV transmission among this high-risk group. "If we want to talk about HIV prevention, then we cannot afford to ignore any group," Nicholas Muraguri, head of the National AIDS and Sexually Transmitted Infections Control Programme, told IRIN/PlusNews, adding that the policy would treat drug addiction as a health issue rather than a criminal justice issue. "We want to provide needle exchange, methadone for treatment and condoms," he said.
Kenya's change in approach to IDUs follows a similar turnaround by the US President's Emergency Plan for AIDS Relief (PEPFAR), which recently changed its policy of excluding needle exchange and opioid substitution therapy programmes from funding.
The biomedical research community is reacting with concern to a proposal from the National Institutes of Health (NIH) to clamp down on financial conflicts of interest in research. In a flood of comments, many groups and some individual scientists say NIH is asking investigators to report irrelevant information. Although they agree reform is needed, many urge NIH to narrow the proposal. They also think the government should create a central database for disclosing conflicts to the public.
In May, NIH proposed several changes to a 1995 Public Health Service (PHS) conflicts of interest regulation. They included lowering the threshold for reporting industry income (from $10,000 to $5000 annually) and requiring investigators to report to their institutions all financial interests related to their job. Institutional officials would then scan these reports for conflicts with an NIH-funded project and, when appropriate, disclose the conflicts publicly on their Web sites. NIH wants investigators to report not only industry payments, but also income from non-profit organizations (except universities).
NIH received more than 170 comments by yesterday's deadline, the bulk from academic institutions, societies, and individual scientists. Many concerns are summed up in an 11-page letter from the Association of American Medical Colleges (AAMC), the Association of American Universities (AAU), and two other university organizations. The groups worry about "onerous regulations" that "create a glut of policies that increase activity without adding protections" and "erode ... trust."
To gauge the current commitment to scientific research in the United States of America (US), we compared federal research funding (FRF) with the US gross domestic product (GDP) and industry research spending during the past six decades. In order to address the recent globalization of scientific research, we also focused on four key indicators of research activities: research and development (R&D) funding, total science and engineering doctoral degrees, patents, and scientific publications. We compared these indicators across three major population and economic regions: the US, the European Union (EU) and the People's Republic of China (China) over the past decade. We discovered a number of interesting trends with direct relevance for science policy. The level of US FRF has varied between 0.2% and 0.6% of the GDP during the last six decades. Since the 1960s, the US FRF contribution has fallen from twice that of industrial research funding to roughly equal. Also, in the last two decades, the portion of the US government R&D spending devoted to research has increased. Although well below the US and the EU in overall funding, the current growth rate for R&D funding in China greatly exceeds that of both. Finally, the EU currently produces more science and engineering doctoral graduates and scientific publications than the US in absolute terms, but not per capita. This study's aim is to facilitate a serious discussion of key questions by the research community and federal policy makers. In particular, our results raise two questions with respect to: a) the increasing globalization of science: "What role is the US playing now, and what role will it play in the future of international science?"; and b) the ability to produce beneficial innovations for society: "How will the US continue to foster its strengths?"
Biomedical researchers have had plenty of time to ponder the NIH's new and far tougher set of standards on what personal financial information has to be disclosed--and they're not at all happy. The agency's deadline for comments passed last week, and they've been deluged with complaints and suggestions. The new rules include a lower threshold for what's considered relevant. Any industry income above $5,000 has to be exposed to sunshine. And all financial interests linked to their research jobs have to be revealed to the institutions they work for, making them fair game for a public airing on an easily accessible website.
But critics point out that the income requirements cover all sources of revenue, not just money from industry sources that could theoretically inspire a conflict of interest, according to a report in Science magazine. And the posted remarks include plenty of angry comments about just how onerous and expensive the new financial disclosure rules could prove if they're allowed to stand as written. Others point out that offenders may try to slip through the net by jumping to a new job, something that one observer noted merits a special, public registry for all offenders. But that's not likely to be greeted with much enthusiasm from investigators, either.
The recent release of positive results from a microbicide trial in South Africa have kick-started discussions between scientists, activists and community workers about the quickest and most responsible way of getting a product into women's hands.
The trial by the Centre for the AIDS Programme of Research in South Africa (CAPRISA) found that a vaginal gel containing tenofovir, an antiretroviral (ARV) drug, was 39 percent effective at reducing women's risk of contracting HIV during sex. In other parts of the world, such results might not be cause for celebration, but in South Africa, and particularly in hard-hit KwaZulu-Natal Province, where the trial was conducted, even such partial effectiveness could prevent 1.3 million new HIV infections over the next two decades and avert over 800,000 deaths, according to mathematical modelling.
"The discomfort we all have is that if this [product] is working, shouldn't we be pushing its use as quickly as possible?" said Prof Helen Rees, director of the Reproductive Health and HIV Research Unit (RHRU) of Witwatersrand University, at a meeting about the CAPRISA trial results in Johannesburg.
Representatives from various sectors in South Africa's AIDS community attended the meeting convened by the South African National AIDS Council, RHRU, and the Treatment Action Campaign (TAC), a local lobby group, to discuss the implications of the results. While some participants raised concerns about whether a female-controlled HIV prevention product might give men an excuse not to use condoms, most wanted to know what the complex trial results would mean for women in their communities, how soon it could be on pharmacy shelves, and what it would cost. Rees explained that South Africa's regulatory authority, the Medicines Control Council (MCC), will probably demand confirmatory results from a second study before approving registration of a microbicide product containing tenofovir. "It's still possible that some of this result was due to chance," she said.
Three trials of prevention methods using ARVs are ongoing in South Africa. The VOICE trial is testing a tenofovir gel, as well as a daily oral dose of tenofovir, and another ARV called truvada, among 5,000 HIV-negative women from multiple sites in South Africa and elsewhere in Africa. A trial called FEM-PrEP is also assessing a daily truvada pill for preventing HIV infection in women and a third trial, called iPrEx, is evaluating the same oral regimen of truvada for preventing HIV among men who have sex with men. But as none of these trials are using the same regimen as the CAPRISA trial, Rees said they were unlikely to produce confirmatory results that could be used to seek product registration.
Four years ago, many in public health predicted that a vaccine for a sexually transmitted disease would be a hard sell for the parents of teenage girls -- even one that prevents cervical cancer later in life.
They were right. In Minnesota, only about 16 percent of teenage girls have gotten all three of the shots needed to protect against HPV, or human papillomavirus, according to data from the Minnesota Department of Health. About one-third have received at least one, about the same as nationally. "Now, even the public health and vaccine people are saying this is slower than we should be tolerating," said Dr. Levi Downs, a cancer expert at the University of Minnesota who researched the vaccine and who has received funding from the manufacturer.
The vaccine has faced an uphill battle. It's expensive, about $300 -- a problem for those with limited or no health insurance -- and requires three shots over six months. Unlike virtually all other childhood immunizations, it's not required for school. But the biggest problem, say doctors on the front lines, is convincing parents that their kids are at risk for a sexually transmitted infection.
King Mswati has come into criticism from Aids campaigners in the past for promoting polygamy Aids activists in Swaziland have criticised a top adviser to King Mswati III for saying the country's HIV epidemic is being exaggerated for the benefit of pharmaceutical firms.
Prince Mangaliso said public awareness campaigns against HIV amounted to little more than scare tactics. He added that male circumcision was no more a preventative measure than bathing after sexual intercourse.
Swaziland For Positive Living told the BBC the remarks were "irresponsible". According to UNAids, Swaziland - Africa's last absolute monarchy - has one of the highest levels of HIV infections in the world, with a prevalence rate of 26% in the adult population.
North Georgia health departments are now offering a free vaccine for HPV, a sexually transmitted disease that is the leading cause of cervical cancer. Federal economic stimulus funding has allow the North Georgia public health departments -- including those in Catoosa, Dade and Walker counties -- to offer the vaccine to children up to age 18 for the next 12 to 18 months, said Stacy Henderson, registered nurse and clinical nurse coordinator at the Catoosa County Health Department. The vaccine is approved for boys and girls, from ages 9 to 26. "The important thing is to really get this vaccine before they're sexually active, before introducing any of these viruses," she said.
Gardasil is the first vaccine to protect against some strains of HPV. The vaccine protects against two strains of HPV that cause 70 percent of cervical cancers and two other strains of the virus that cause 90 percent of genital warts cases, according to the drug's manufacturer, Merck & Co. Some local gynecologists say the vaccine could help wipe out the cancer. But the HPV vaccine -- given in the form of three doses over six months -- has worried some parents who hesitate to vaccinate their children against a disease transmitted through sex, local doctors said.
Almost two-thirds of patients whose infection with HIV was diagnosed late had virus that uses the CCR5 co-receptor, and could therefore potentially benefit from taking a treatment regimen that includes maraviroc (Celsentri), Austrian investigators report in the 24th August edition of AIDS.
Maraviroc was recently approved for use in first-line HIV treatment, although it is most widely used in extensively treated patients. However, the investigators believe that the drug could be especially beneficial for patients who are diagnosed late. Some research suggests that the drug can boost CD4 cell count, even when viral load is not suppressed.
HIV uses one of two co-receptors to attach to human cells: CCR5 or CXCR4. Additionally, patients may sometimes have what is called mixed or dual tropism virus, and this occurs when both co-receptors are present. The presence of CXCR4 and dual/mixed tropism-using virus is associated with late-stage HIV disease and a low CD4 cell count. Little is known about the re-receptor types that are present in patients whose HIV infection is diagnosed late (a CD4 cell count below 200 cells/mm3).
Therefore Austrian investigators analysed the co-receptors of 50 patients with late HIV diagnosis between 2004 and 2007. To see if any factors were associated with the presence of particular co-receptors, information was also gathered on the patients' baseline CD4 cell count and viral, as well as their demographic details. A total of 31 patients (62%) had HIV that used the CCR5 co-receptor.
Clad in a yellow gown, blue foot covers, hair net, face mask and latex gloves, Paula Cannon pushed open the door to the animal room. "I hate this smell," she said, wrinkling her nose. The stink came from scores of little white mice scurrying about in cages. Some of the cages were marked with red biohazard signs, indicating mice that had been injected with HIV. Yet, in some of the animals -- ones with a small genetic change -- the virus never took hold. Like mouse, like man? Maybe so.
In early 2007, a patient in Berlin needed a bone marrow transplant to treat his leukemia. He was also HIV positive, and his doctor had an idea: Why not use the marrow from one of the rare individuals who are naturally resistant to HIV and try to eradicate both diseases at once? It worked. Sixty-one days after the patient's transplant, his virus levels were undetectable, and they've stayed that way.
Since news of the man's cure broke, HIV patients have been telephoning doctors to ask for bone marrow transplants. But it's not that simple. The treatment is too risky and impractical for widespread use.
Treatment with tenofovir has an adverse impact on kidney function, but the clinical significance of this is modest, according to the results of a systematic review and meta-analysis conducted by an international team of investigators and published in the September 1st edition of Clinical Infectious Diseases.
The investigators looked at the results of 17 studies involving a total of 11,000 patients. All the studies compared outcomes in patients taking tenofovir-containing regimens to those seen in patients whose HIV treatment did not include this drug. Loss of kidney function was significantly greater amongst patients who took a combination of drugs that included tenofovir. In addition, those taking tenofovir were more likely to develop kidney disease. However, the investigators comment: "Although our review identified a significant loss of renal function associated with TDF [tenofovir] use, the clinical magnitude of this effect was modest."
Tenofovir (Viread, also in the combination pills Truvada and Atripla) is a widely-used antiretroviral drug in both industrialised and resource-limited settings. The clinical trials that formed the basis of the drug's formal approval showed that it was very safe. Nevertheless, after its licensing, case reports were published showing that some patients treated with the drug had developed kidney dysfunction or disease. Moreover, several observational cohort studies have founded that approximately 1% of tenofovir-treated patients per year develop such severe kidney dysfunction that they cease therapy with the drug.
When the first positive results of a research trial for an antiretroviral-based vaginal microbicide gel were announced at the International AIDS Conference in Vienna this July, it marked a significant thinning of the line between HIV treatment and prevention. The same agents that had been designed and developed to slow the virus's proliferation within the human body now had the potential to be used to help bar it from successfully setting up shop in the first place.
The findings also suggested that the line between HIV-negative and HIV-positive might soon become much thicker, especially in the developing world, where the virus is mostly spread through heterosexual sex.
"In Africa, one in 10 girls contracts HIV by the time she's 16," notes Yasmin Halima, director for the Global Campaign for Microbicides. "But by the age of 24, one in two will have the virus. This is why these results are so very appealing."
New studies in Uganda show that married or co-habiting couples today stand a higher risk of contracting HIV than single or young people. This marks an astonishing shift in the pandemic's infection patterns in the country. Uganda's HIV/AIDS prevention campaigns, since the onset of the pandemic in the early 1980's, have been premised on the perception that young people between 15-24 years were at a higher risk of infection than older age groups, particularly those in the 30-40 age bracket.
"There has been a shift in the epidemic from people in single casual relationships to those in long-term relationships," says the March 2010 Uganda epidemic status report by the Uganda AIDS Commission funded by UNAids. "43 percent of new HIV infections are among monogamous relationships while 64 percent are among persons reporting multiple partnerships and their partners."
The Director General of the Uganda AIDS Commission Dr Kihumuro Apuuli said: "In our studies four or five years ago, the main new infections were among [people aged] 20 to 25. But now there is a shift upwards and the most new infections are among people between 30 and 34 years, and 40 and 45 years." The UNAIDS 2009 epidemic report concurs with these findings in Uganda.
Studies show that between 1995 and 2006, the proportion of men and women who reported having had sex with someone other than their spouse increased from 12 percent to 16 percent for women and from 29 percent to 36 percent for men. The Uganda AIDS Commission unveiled study results that show that 42 percent of the 130,000 new HIV infections between 1996 and 2005 were among married couples.
Russian President Dmitry Medvedev said on Tuesday he will support the leader of U2 Bono in his efforts to fight HIV/AIDS. Medvedev met with Bono ahead of the U2 concert due in Moscow on August 25. Bono told the Russian president that the problem of transferring the infection from mother to child can be solved and asked Medvedev to recommend Russian companies, which could help in working on the issue.
"This is a good program, a very concrete program and a very good way to solve problems," Medvedev said. "We will think of how Russia may participate to solve these problems," he continued. Bono actively works in fighting HIV and AIDS around the world. He also organizes many charity events along with the other members of U2 as well as other celebrities.
The State Research Center for Virology and Biotechnology, Vector, has successfully accomplished the development of a candidate HIV vaccine and obtained permission to test it on volunteers, the center's press service said in July.
Almost a million South Africans are already on lifelong antiretroviral (ARV) treatment and this number is supposed to triple in the next decade if the South African government keeps to its implementation plan. But the prospect of the government being able to meet its target of treating 80 percent of those who need it by 2011 is being threatened by a lack of funds. A number of organisations and prominent officials in the AIDS field condemned the "flat-lining" of donor funds at the recent international AIDS conference in Vienna.
In 2009, donors contributed 7.6 billion dollars to the international fight against HIV and AIDS, slightly down from 7.7 billion dollars in 2008, according to the Kaiser Family Foundation. Yet in order for more people to be put on life-saving medication, more money needs to be spent. South Africa alone needs an extra 272 million dollars a year to reach all those who need antiretroviral treatment. Scenario planning by the South African treasury department indicates that the demand for treatment and care will peak in 2021, when the country will need some four billion dollars to provide these services.
Researchers from The Wistar Institute recently reported that a human adenovirus called AdHu26, once thought uncommon, is not so rare after all. This could be bad news for scientists eager to use engineered AdHu26 human adenoviruses as vaccines against HIV and other diseases. In this approach, adenoviruses, which commonly cause respiratory-tract infections, are rendered relatively harmless before being used as vectors to deliver genes from pathogens, which then stimulate the body to generate an immune response. Yet studies show that a viral vector may be less effective if the vector is based on a type common in a population, because humans will have previously developed immunity to it.
"AdHu26 is considered by some to be rare in nature and thus there should be less pre-existing immunity. Dr. Hildegund Ertl [at Wistar] is claiming this is incorrect at least for certain human populations," says Mark J. Newman, Ph.D., Vice President of Research and Development at GeoVax Labs, headquartered in Smyrna, Georgia. In its quest for an HIV vaccine, GeoVax has turned for help to a poxvirus vector called Modified Vaccinia Ankara (MVA), originally developed as a safer smallpox vaccine.
New research about a steep drop in circumcisions made headlines this past week. According to one federal researcher, circumcision rates in U.S. hospitals slid from 56 percent in 2006 to fewer than a third of boys born last year. Doctors caution that those numbers aren't definitive for instance, they don't include circumcisions not covered by insurance policies or circumcisions performed in religious settings.
But Dr. Douglas Diekema, a pediatrics bioethicist at the University of Washington, tells NPR's Audie Cornish there's no doubt about the overall trend. "I think all of us agree there probably is a decrease in the number of circumcisions over time, and that's probably a result of a number of factors," Diekema says. "About 10 years ago, the American Academy of Pediatrics came out with a policy statement that was fairly neutral on whether circumcisions should be recommended for newborns or not," says Diekema. "And that probably changed the way physicians were talking to their families."
In many states, Medicaid stopped covering the procedure as a result of that policy statement. And many insurance companies followed suit, meaning that more and more families might have decided to forgo circumcision just because of the expense.
The inclusion of male circumcision in the comprehensive HIV prevention package early this year was hailed as a step in the right direction in the fight against HIV-Aids in South Africa. But there is confusion as to what age boys should be circumcised. Section 12(8) of the Act stipulates that circumcision of male children under the age of 16 is prohibited, except when it is performed for religious purposes in accordance with the practices of the religion concerned or for medical reasons on the recommendation of a medical practitioner.
Brian Honermann, researcher at NGO Section 27, said: "The confusion is based on a poor reading of the Act. At present, there is no legal limitation beyond standard informed-consent requirements that prohibits the provision of elective neo-natal medical male circumcision. "The Children's Act expressly allows for circumcision of males under the age of 16 when they are conducted for medical reasons on the recommendation of a medical practitioner," he said.
Studies conducted in 2005 in South Africa and other sub-Saharan countries showed that male circumcision can provide 58 percent protection against acquiring HIV infection. After the findings were released most countries adopted the procedure as part of their HIV-prevention package.
One of the cheapest and most commonly used drugs for treating HIV in Africa - nevirapine - has been associated with an increased risk of treatment failure in a retrospective South African study.
The study, published in the August 15 issue of the Journal of AIDS, looked at adult patients given antiretroviral (ARV) treatment at public sector clinics in South Africa's Western Cape Province between 2001 and 2006. It found that the use of single-dose nevirapine for the prevention of mother-to-child transmission (PMTCT) increased a patient's chances of treatment failing by nine-fold. Taking the drug as part of a first-line treatment regimen doubled a patient's risk of treatment failure and having to be switched to much more expensive second-line ARVs.
Nevirapine is often prescribed for HIV-positive women of child-bearing age because the alternative - efavirenz - has been linked to birth defects.
The study found that a CD4 count of less than 150 at the time of starting ARV treatment, and interruptions in treatment, were also associated with poorer treatment outcomes. Experts have long known that patients who interrupt ARV treatment or miss doses are more likely to develop drug resistance and stop responding to treatment. A number of studies have also found that patients who start taking ARVs late, when their CD4 count is low, are less likely to do well on treatment.
U.S. President Barack Obama wants Congress to boost funding for AIDS virus services and research, according to a letter the president sent Friday to House of Representatives Speaker Nancy Pelosi (D., Calif.). Obama is seeking $400 million from Congress to help fight the AIDS virus, train health-care workers and to increase an account for state high-risk health insurance pools, according to a copy of a letter the White House released Friday. The request is part of amendments to Obama's fiscal year 2011 budget and would be offset by reducing funding in other areas.
About $55 million would go toward AIDS virus prevention, services and research while $250 million would be to help enhance health-care training programs the government operates. The remainder would be to boost state high-risk insurance pools and health insurance information for consumers.
HIV-1 is present in anatomical compartments and bodily fluids. Most transmissions occur through sexual acts, making virus in semen the proximal source in male donors. We find three distinct relationships in comparing viral RNA populations between blood and semen in men with chronic HIV-1 infection, and we propose that the viral populations in semen arise by multiple mechanisms including: direct import of virus, oligoclonal amplification within the seminal tract, or compartmentalization. In addition, we find significant enrichment of six out of nineteen cytokines and chemokines in semen of both HIV-infected and uninfected men, and another seven further enriched in infected individuals. The enrichment of cytokines involved in innate immunity in the seminal tract, complemented with chemokines in infected men, creates an environment conducive to T cell activation and viral replication. These studies define different relationships between virus in blood and semen that can significantly alter the composition of the viral population at the source that is most proximal to the transmitted virus.
As antiretroviral treatment of HIV infection has become increasingly accessible, attention has focused on whether these drugs can used for prevention because of increased tolerability of newer medications, decreased cost, and the limitations of other approaches. We review the status of antiretroviral HIV prevention, including chemoprophylaxis, as well as the effects of treatment of infected individuals on prevention. It is possible that the life-saving agents that have transformed the natural history of AIDS can be a critical component of HIV prevention efforts, but their ultimate role in affecting HIV transmission dynamics remains to be defined.
Vaginal gels may act as physical barriers to HIV following semen deposition. However, the extent and significance of this effect are not well understood. During male-to-female sexual transmission of HIV, semen containing infectious HIV is present within the lower female reproductive tract. In cases where a topical gel has previously been applied to the vaginal epithelium, virions must move through gel layers before reaching vulnerable tissue. This additional barrier could affect the functioning of anti-HIV microbicide gels and placebos. To better understand HIV transport in gels, we: (1) quantified diffusion coefficients of HIV virions within semi-solid delivery vehicles; and (2) tested the barrier functioning of thin gel layers in a Transwell system. Two gels used as placebos in microbicides clinical trials, hydroxyethyl cellulose (HEC) and methylcellulose (MC), were found to hinder HIV transport in vitro. The diffusion coefficients for HIV virions in undiluted HEC and MC were 4 +/- 2 * 10-12 and 7 +/- 1 * 10-12 cm2/s, respectively. These are almost 10,000 times lower than the diffusion coefficient for HIV in water. Substantial gel dilution (80%:diluent/gel, v/v) was required before diffusion coefficients rose to even two orders of magnitude lower than those in water. In the Transwell system, gel layers of approximately 150-[micro]m thickness reduced HIV transport. There was a log reduction in the amount of HIV that had breached the Transwell membrane after 0-, 4-, and 8-h incubations. The ability of a gel to function as a physical barrier to HIV transport from semen to tissue will also depend on its distribution over the epithelium and effects of dilution by vaginal fluids or semen. Results here can serve as a baseline for future design of products that act as barriers to HIV transmission. The potential barrier function of placebo gels should be considered in the design and interpretation of microbicides clinical trials.
Background The National Institute of Allergy and Infectious Diseases has launched the HIV-1 Human Protein Interaction Database in an effort to catalogue all published interactions between HIV-1 and human proteins. In order to systematically investigate these interactions functionally and dynamically, we have constructed an HIV-1 human protein interaction network. This network was analyzed for important proteins and processes that are specific for the HIV life-cycle. In order to expose viral strategies, network motif analysis was carried out showing reoccurring patterns in virus-host dynamics.
Results Our analyses show that human proteins interacting with HIV form a densely connected and central sub-network within the total human protein interaction network. The evaluation of this sub-network for connectivity and centrality resulted in a set of proteins essential for the HIV life-cycle. Remarkably, we were able to associate proteins involved in RNA polymerase II transcription with hubs and proteasome formation with bottlenecks. Inferred network motifs show significant over-representation of positive and negative feedback patterns between virus and host. Strikingly, such patterns have never been reported in combined virus-host systems.
Conclusions HIV infection results in a reprioritization of cellular processes reflected by an increase in the relative importance of transcriptional machinery and proteasome formation. We conclude that during the evolution of HIV, some patterns of interaction have been selected for resulting in a system where virus proteins preferably interact with central human proteins for direct control and with proteasomal proteins for indirect control over the cellular processes. Finally, the patterns described by network motifs illustrate how virus and host interact with one another.
Positive prevention which focuses on prevention of HIV transmission from those already infected to those uninfected is an important issue for HIV prevention. A self-administered questionnaire on sexual practice survey of HIV-infected patients attending HIV clinics was undertaken. Of the 1160 patients, 53% knew their HIV status after being ill and 59% believed that they got infection from their regular sexual partner. In 3 months prior to the survey, 18% reported unprotected sex. Unprotected sex significantly decreased in people having adequate condoms but increased in those who believed that their sexual partners were already infected. Effect of disclosure of HIV status on unprotected sex depended on whether patients were men or women. Nondisclosure HIV-positive men claimed to have less unprotected sex than their counterpart, HIV-positive women. Factors related to unprotected sex should be addressed and sexual health must be integrated and promoted in HIV health care.
Community-based prevention leads to an increase in condom use and a reduction in sexually transmitted infections (STIs) among men who have sex with men (MSM) and female sex workers (FSW): the Frontiers Prevention Project (FPP) evaluation results
Background India has an estimated 2.0 million to 3.1 million people living with HIV; it has the highest number of HIV-positive people in Asia and ranks third in the world. The Frontiers Prevention Project (FPP) was implemented in 2002 to conduct targeted prevention intervention geared towards female sex workers (FSW) and men who have sex with men (MSM) in the state of Andhra Pradesh (AP). This paper reports the overall changes in behaviour and STI outcomes between 2003/4 and 2007 and also describes the changes attributed to the FPP.
Methods The evaluation used two cross-sectional surveys among MSM and FSW at 24 sites in AP. Surveys were implemented using a similar methodology. Univariate analyses were conducted by comparing means: baseline vs. four-year follow-up and FPP vs. non-FPP. For both MSM and FSW, random and fixed-effects logit regression models at the site level were estimated for condom use with last partner, syphilis sero-positivity and HSV 2 sero-positivity. In addition, for FSW we estimated models for condom use with regular partner, and for MSM we estimated models for condom use with last female partner.
Results Among MSM, fixed-effects analysis revealed that FPP was positively correlated with the probability of condom use with last female sexual partner and negatively correlated with the individual probability of sero-positivity to syphilis and HSV 2. Among FSW, the FPP intervention was significantly correlated with increased condom use with regular partners and with lower probability of STI sero-positivity.
Discussion Important changes in behaviours related to an increase in prevention activities translated to reductions in STI sero-prevalence in AP, India. In contrast with non-FPP sites, the FPP sites experienced an intense community approach as part of the FPP intervention, and the general increase in condom use and its effect on STI sero-prevalence reflected the efficacy of these intense prevention activities focused on key populations in AP.
Background One-third of all new HIV infections in Cambodia are estimated to be due to mother-to-child transmission. Although the Ministry of Health adopted a policy of provider-initiated HIV testing and counseling (PITC), nearly a quarter of pregnant mothers were not tested in 2007. Greater acceptance of HIV testing is a challenge despite Cambodia's adoption of the PITC policy.
Methods A hospital-based quantitative and cross-sectional survey was conducted to assess the prevalence of and barriers to HIV testing among mothers after delivery at the National Maternal and Child Health Center in Phnom Penh. The Center is one of the largest maternal and child care hospitals in the country to offer PITC services. All 600 eligible mothers who were admitted to the hospital after delivery from October to December 2007 were approached and recruited. Data were collected via a semi-structured questionnaire.
Results The prevalence of HIV testing among women who delivered at the hospital was 76%. In multivariate logistic regression, factors such as the perceived need to obtain a partner's permission to be tested (OR=0.27, 95% CI=0.14-0.51, p<0.01), the lack of knowledge about HIV prevention and treatment (OR=0.38, CI=0.22-0.66, p<0.01), and the lack of access to ANC services (OR=0.35, 95% CI=0.21-0.58, p<0.01) were found to be the main barriers to HIV testing.
Conclusion To achieve greater acceptance of HIV testing, counseling on HIV prevention and treatment must be provided not only to mothers but also to their partners. In addition, utilization of non-laboratory staff such as midwives to provide HIV testing services in rural health facilities could lead to the greater acceptance of HIV testing.
Background Topical microbicides, used by women to prevent the transmission of HIV and other sexually transmitted infections are urgently required. Dendrimers are highly branched nanoparticles being developed as microbicides. However, the anti-HIV and HSV structure-activity relationship of dendrimers comprising benzyhydryl amide cores and lysine branches, and a comprehensive analysis of their broad-spectrum anti-HIV activity and mechanism of action have not been published.
Methods and Findings Dendrimers with optimized activity against HIV-1 and HSV-2 were identified with respect to the number of lysine branches (generations) and surface groups. Antiviral activity was determined in cell culture assays. Time-of-addition assays were performed to determine dendrimer mechanism of action. In vivo toxicity and HSV-2 inhibitory activity were evaluated in the mouse HSV-2 susceptibility model. Surface groups imparting the most potent inhibitory activity against HIV-1 and HSV-2 were naphthalene disulfonic acid (DNAA) and 3,5-disulfobenzoic acid exhibiting the greatest anionic charge and hydrophobicity of the seven surface groups tested. Their anti-HIV-1 activity did not appreciably increase beyond a second-generation dendrimer while dendrimers larger than two generations were required for potent anti-HSV-2 activity. Second (SPL7115) and fourth generation (SPL7013) DNAA dendrimers demonstrated broad-spectrum anti-HIV activity. However, SPL7013 was more active against HSV and blocking HIV-1 envelope mediated cell-to-cell fusion. SPL7013 and SPL7115 inhibited viral entry with similar potency against CXCR4-(X4) and CCR5-using (R5) HIV-1 strains. SPL7013 was not toxic and provided at least 12 h protection against HSV-2 in the mouse vagina.
Conclusions Dendrimers can be engineered with optimized potency against HIV and HSV representing a unique platform for the controlled synthesis of chemically defined multivalent agents as viral entry inhibitors. SPL7013 is formulated as VivaGel(R) and is currently in clinical development to provide protection against HIV and HSV. SPL7013 could also be combined with other microbicides.
Intravaginal insertion is often associated with the concept of 'dry' sex. All HIV-prevention microbicides tested to date have been vaginally applied lubricant-based gels. In this paper, we examine whether the use of intravaginal insertions could be in conflict with the introduction of vaginal microbicide gels. The Africa Centre site was part of the Microbicides Development Programme evaluating PRO2000/5 microbicide gel. We conducted in-depth-interviews and focus-group discussions with women enrolled in the trial as well as women and men from the community. The analysis focused on people's knowledge of intravaginal insertion in the community and trial participants' experience of using trial gels. Intravaginal use of a variety of products was widely acknowledged. We found that the experience of using trial gels -- which made sex 'hot', 'tight' and 'dry' -- matched the desired outcomes of intravaginal insertion. We found that vaginal 'dryness' described the removal of excessive amounts of unusual discharge, rather than the removal of normal vaginal secretions and that intravaginal insertion is not exclusively associated with a desire for 'dry' sex. Study findings provide evidence that vaginal microbicide gels may be more acceptable in communities where intravaginal insertion is practiced than was previously thought.
Previous research in India indicates that there is little communication within marriage about sex. Lack of communication about safe sexual behaviours may increase couples' vulnerability to HIV. This study explores couple level sexual communication and socio-cultural norms that influence couples' communication about sex and its implications for HIV prevention. Data derive from in-depth interviews at two points in time with 10 couples. Secondary qualitative analyses of the interviews were conducted using inductive and deductive coding techniques. Half of the couples described improved communication about sex and HIV and AIDS after participation in the clinical trial and/or acceptability study, as well as increased sexual activity, improved relationships by alleviating doubts about their partner's fidelity and forgiving their partners. The findings show that creating safe spaces for couples where they can ask frank questions about HIV and AIDS, sex and sexuality potentially can improve couples' communication about sex and reduce their risk for HIV infection.
Background Substance use during sex is associated with sexual risk behavior among men who have sex with men (MSM), and MSM continue to be the group at highest risk for incident HIV in the United States. The objective of this study is to test the efficacy of a group-based, cognitive-behavioral intervention to reduce risk behavior of substance-using MSM, compared to a randomized attention-control group and a nonrandomized standard HIV-testing group.
Methods and Findings Participants (n = 1,686) were enrolled in Chicago, Los Angeles, New York City, and San Francisco and randomized to a cognitive-behavioral intervention or attention-control comparison. The nonrandomized group received standard HIV counseling and testing. Intervention group participants received six 2-h group sessions focused on reducing substance use and sexual risk behavior. Attention-control group participants received six 2-h group sessions of videos and discussion of MSM community issues unrelated to substance use, sexual risk, and HIV/AIDS. All three groups received HIV counseling and testing at baseline. The sample reported high-risk behavior during the past 3 mo prior to their baseline visit: 67% reported unprotected anal sex, and 77% reported substance use during their most recent anal sex encounter with a nonprimary partner. The three groups significantly (p<0.05) reduced risk behavior (e.g., unprotected anal sex reduced by 32% at 12-mo follow-up), but were not different (p>0.05) from each other at 3-, 6-, and 12-mo follow-up. Outcomes for the 2-arm comparisons were not significantly different at 12-mo follow-up (e.g., unprotected anal sex, odds ratio = 1.14, confidence interval = 0.86-1.51), nor at earlier time points. Similar results were found for each outcome variable in both 2- and 3-arm comparisons.
Conclusions These results for reducing sexual risk behavior of substance-using MSM are consistent with results of intervention trials for other populations, which collectively suggest critical challenges for the field of HIV behavioral interventions. Several mechanisms may contribute to statistically indistinguishable reductions in risk outcomes by trial group. More explicit debate is needed in the behavioral intervention field about appropriate scientific designs and methods. As HIV prevention increasingly competes for behavior-change attention alongside other "chronic" diseases and mental health issues, new approaches may better resonate with at-risk groups.
Background The efficacy of tenofovir disoproxil fumarate (TDF) as part of combination antiretroviral treatment (ART) has been demonstrated in several randomized, controlled trials. However, an increasing number of case reports suggest that TDF use may be associated with significant nephrotoxicity. Our objective was to determine the renal safety of TDF-containing ART regimens for HIV-infected individuals.
Methods MEDLINE, EMBASE, Global Health, Scopus, Biosis Previews, Cochrane Library, Web of Science, and existing systematic reviews were searched. Prospective studies comparing TDF-containing with non-TDF containing ART regimens were selected for inclusion. We extracted data on study characteristics, participant characteristics, therapeutic interventions, renal function, bone density, and fracture rates.
Results A total of 17 studies (including 9 randomized, controlled trials) met the selection criteria. Median sample size was 517 participants. Constituent ART regimens were diverse. There was a significantly greater loss of kidney function among the TDF recipients, compared with control subjects (mean difference in calculated creatinine clearance, 3.92 mL/min; 95% confidence interval [CI], 2.13-5.70 mL/min), as well as a greater risk of acute renal failure (risk difference, 0.7%; 95% CI, 0.2-1.2). There was no evidence that TDF use led to increased risk of severe proteinuria, hypophosphatemia, or fractures.
Conclusions Although TDF use was associated with a statistically significant loss of renal function, the clinical magnitude of this effect was modest. Our findings do not support the need to restrict TDF use in jurisdictions where regular monitoring of renal function and serum phosphate levels is impractical.
During HIV-1 entry, binding of the viral envelope glycoprotein gp120 to the cellular CD4 receptor triggers conformational changes resulting in exposure of new epitopes, the highly conserved CD4-induced (CD4i) epitopes that are essential for subsequent binding to chemokine receptors CCR5 or CXCR4. Due to their functional conservation, CD4i epitopes represent attractive viral targets for HIV-1 entry inhibition. The aim of this study was to select peptide ligands for CD4i epitopes on native dualtropic (R5X4) HIV-1 envelope (Env) glycoproteins by phage display. Using CD4 activated retroviral particles carrying Env from the R5X4 HIV-1 89.6 strain as target, we performed screenings of random peptide phage libraries under stringent selection conditions. Selected peptides showed partial identity with amino acids in the extracellular domains of CCR5/CXCR4 including motifs rich in tyrosines and aspartates at the N-terminus known to be important for gp120 binding. A synthetic peptide derivative (XD3) corresponding to the most frequently selected phage was optimized for Env binding on peptide arrays. Interestingly, the optimized peptide could bind specifically to gp120 derived from HIV-1 strains with different coreceptor usage, competed with binding of CD4i-specific monoclonal antibody (mAb) 17b and interfered with virus entry of both, a CCR5 using (R5) and a CXCR4 using (X4) Env pseudotyped virus. This peptide ligand therefore points at unique properties of CD4i epitopes shared by gp120 with different coreceptor usage and could thus serve to provide new insight into the conserved structural details essential for coreceptor binding for further drug development.
The HIV pandemic has historically been thought of as either concentrated in specific populations -- such as gay men, injection drug-users, sex workers -- or generalized across the entire population in sub-Saharan Africa and the Caribbean. But as more and better epidemiological data has become available, the evidence is clear: men who have sex with men (MSM), regardless of whether or not they identify as gay, also are at the core of those generalized epidemics.
MSM in developing countries are 19 times more likely to be infected with HIV than the general population, according to a 2007 literature review. Even in Africa, at the heart of the pandemic, in Malawi, 21 percent of MSM are infected with the virus compared with 11 percent of the general population, whereas Zambia's rates are 33 percent versus 15 percent, respectively, says Chris Beyrer, director of the Johns Hopkins Center of Public Health and Human Rights.
"The argument that gay and bisexual men are a trivial sideshow in the global fight against AIDS is wrong," he told the Global Forum on MSM and HIV, an advocacy network that met this summer prior to the International AIDS Conference in Vienna, Austria.
Human immunodeficiency virus (HIV), the virus that causes AIDS, did not originate in humans. Instead, the most common variant, HIV1, is thought to have originated as a simian immunodeficiency virus (SIV) in apes and to have jumped the species barrier from apes to humans sometime in the first half of the 20th century. Similarly, HIV2 -- a related but less virulent virus -- arrived in humans after jumping from a different primate species, the sooty mangabey. SIVs have also jumped between different primate populations, both in the wild and in animals kept in captivity for research purposes. But, just how SIV was able to gain a toehold in new, genetically distinct species has been something of a puzzle; laboratory experiments suggest that there exist several host genes that should, in theory, pose a formidable barrier to interspecies viral transmission. The genes encode what are known collectively as restriction factors, and they are thought to have evolved specifically to prevent movement of viruses between species. Understanding how viruses overcome these barriers to transmission is important for designing both vaccines and treatments. In this issue of PLoS Biology, Andrea Kirmaier, Welkin Johnson, and colleagues provide new insight about the impact the macaque gene TRIM5 makes on cross-species transmission of SIV.
In the 1970s, before SIV was recognized as a potential cross-species contagion, a group of captive rhesus macaques in the United States was accidentally exposed to SIV from sooty mangabeys. The sooty mangabey viral strain, called SIVsm, quickly adapted to its new host, becoming a new, genetically distinct strain called SIVmac. It was subsequently recognized that infected macaques develop an immune deficiency syndrome very similar to that observed in HIV-infected humans. For that reason, SIV-infected macaques are now closely studied as an animal model for HIV disease. But how did SIVsm cross the species barrier in the first place?
One obstacle to cross-species viral transmission is posed by the monkeys' TRIM5 gene, whose protein product, TRIM5[alpha], blocks lentiviruses (the viral family that counts SIV and HIV as members) shortly after they infect a host cell by binding to viral capsid proteins. Johnson's research group had earlier shown that macaques possess several different alleles of the TRIM5 gene, each of which encodes a slightly different TRIM5[alpha] protein. Experiments with cells expressing the different TRIM5 alleles showed that some of the alleles strongly restrict the replication of certain lentiviruses, while others are quite permissive for replication.
Purpose This Funding Opportunity Announcement (FOA), issued by the National Institute of Allergy and Infectious Diseases (NIAID) invites submission of investigator-initiated Program Project (P01) applications. The proposed programs may address scientific areas relevant to the NIAID mission including the biology, pathogenesis, and host response to microbes, including HIV; the mechanisms of normal immune function and immune dysfunction resulting in autoimmunity, immunodeficiency, allergy, asthma, and transplant rejection; and translational research to develop vaccines, therapeutics, and diagnostics to prevent and treat infectious, immune-mediated, and allergic diseases. Each P01 application submitted in response to this FOA must include at least two related research projects that share a common central theme, focus, and/or overall objective.
Mechanism of Support This FOA will utilize the NIH Program Project (P01) grant mechanism.
Funds Available and Anticipated Number of Awards The total amount awarded and the number of awards will depend upon the numbers, quality, duration, and costs of the applications received.
Overview The World Health Organization is pleased to announce the First Global Forum on Medical Devices to be held 9-11 September, 2010 in Bangkok, Thailand. The adoption of the first resolution on health technologies in May 2007 by the World Health Assembly (WHA 60.29) set the framework for an unprecedented focus on health technologies. Health technologies are recognized as essential for the achievement of health-related Millennium Development Goals. Medical devices in particular play a fundamental role in strengthening national health systems and in improving health outcomes. As part of the overall strategy to improve access to safe, effective and appropriate medical devices, WHO has convened the First Global Forum on Medical Devices.
To demonstrate evidence on the need for appropriate evaluation, prioritization, regulation, assessment, management and research strategies on medical devices;
To share knowledge on available resources: guidelines, tools, strategies, policies and best practices at national and regional levels and determine the needs;
To bring together policy makers, professional organizations, funding agencies and key stakeholders to foster interdisciplinary partnerships and cultivate the aim of reaching a common goal of accessible medical devices.
Identification of recommended actions that can be taken for the improvement in availability, accessibility, appropriate selection, assessment, regulation, management, safety and use of medical devices in line with the World Health Assembly resolution (WHO60.29) on health technologies;
Compilation of best practices, available resources, tools and guidelines on medical devices for integration into national health plans;
A network of interdisciplinary professionals who will continue to support the role of medical devices in health systems.
Provisional Programme Link to provisional programme [pdf 296kb]
Registration Participation in the First Global Forum on Medical Devices is by invitation only. Invitations are extended to high level policy makers represented by ministries of health, United Nations organizations and key stakeholders, including users, civil society, funding agencies, international organizations, academic institutions, medical technology industry and media. There are no registration fees for invited participants. No on site registration will be allowed.
RFP Numbers SOL1024982, SOL1025868, SOL1025931, SOL1025940 Closing Date May 31, 2011 LOI Review Dates November 1, 2010 and April 1, 2011
The Bill & Melinda Gates Foundation has made major investments in the development of an HIV vaccine. The Collaboration for AIDS Vaccine Discovery (CAVD) initiative, launched by the foundation in 2006, established a new model of collaboration and cooperation in HIV vaccine research. By supporting vaccine discovery consortia that are separately pursuing novel candidate vaccines but linked by a commitment to sharing of data and materials and supported by a common platform of centralized services, the CAVD enables the bold pursuit of novel vaccine concepts in a supportive and enabling environment. The focus of the CAVD has been on translational research, harnessing knowledge to develop new vaccine concepts and to advance the most promising of them to clinical trials.
The goal of this Request for Proposals (RFP) is to fortify our commitment to translational research, building on current successes while infusing even greater diversity into the pipeline of product concepts for HIV vaccines. In this phase of the CAVD, we will measure success by how rapidly novel ideas and the latest scientific advances are captured as new product concepts, the efficiency with which a diverse portfolio of product concepts is explored, and the extent to which capacity to advance a range of products to clinical trials is ensured through the collective effort of major funders and implementers. While the foundation will continue to invest in innovative early discovery, support the development of advanced products, and invest in an enabling environment including centralized service facilities, this solicitation is focused solely on the diversification of the product concept pipeline, from product conceptualization to clinical trials at the stage of first-in-man.
The approaches under consideration for this call for proposals include the following four topic areas:
HIV Vaccines for Containment at the Portal of Entry
Novel HIV Vaccines to Elicit Protective Antibodies
Replicating Viral Vectors for an HIV Vaccine
Passive Immunization with Human Monoclonal Antibodies for HIV Prevention
At the end of the first decade of the 21st century, the social, behavioral, and economic sciences face extraordinary opportunities to address next-generation research challenges. The landscape is vast and complex, stretching across temporal and spatial dimensions and multiple levels of analysis -- from studying the human brain to implications of decision making in a dynamic and fragmented yet interconnected world. As we look forward 10 or even 20 years, the Directorate for the Social, Behavioral, and Economic Sciences of the National Science Foundation (NSF/SBE) seeks to frame innovative research for the year 2020 and beyond that enhances fundamental knowledge and benefits society in many ways.
This request is part of a process that will help NSF/SBE make plans to support future research. Other activities will include a report by the Directorate's Advisory Committee about the grand challenges facing the SBE sciences over the next decade and recommendations from the Directorate's staff. The insights resulting from this process are threefold: They will inform the substance of future research, the capacities to pursue that research, and the infrastructure to enable investigations that will be increasingly interdisciplinary and international and will involve multiple perspectives and intellectual frameworks, differing scales and contexts, and diverse approaches and methodologies.
As a first step in engaging its community, NSF/SBE invites individuals and groups to contribute white papers outlining grand challenge questions that are both foundational and transformative. They are foundational in the sense that they reflect deep issues that engage fundamental assumptions behind disciplinary research traditions and are transformative because they seek to leverage current findings to unlock a new cycle of research. We expect these white papers to advance SBE's mission to study human characteristics and human behaviors in its Social and Economic Sciences and Behavioral and Cognitive Sciences divisions, as well as to be the nation's resource for understanding the structure and development of science through its Science Resources Statistics division. These white papers must:
Explain the challenge question, capability to be created, or scientific strategy; provide context in terms of recent research results and standing questions in the field; suggest the range of disciplines that may contribute, and indicate the implications for future research within and across disciplines.
Limit the white paper to 2,000 words with a 200-word maximum abstract and up to 3 references to relevant readings.
This update contains a link to AVAC's new publication, Understanding the results of CAPRISA 004. CAPRISA 004 is the landmark trial of the microbicide 1% tenofovir gel, the results of which were released in July 2010. It found that 1% tenofovir gel reduced HIV-negative women's risk of HIV infection by an estimated 39 percent overall. AVAC's new document provides key context for next steps regarding the development of the microbicide 1% tenofovir gel and describes many of the issues that advocates should be monitoring and engaging with in the months to come.
As Understanding the results of CAPRISA 004 explains, there is an urgent need for work on follow-up research on 1% tenofovir gel, regulatory pathways for potential introduction and microbicide pipeline expansion. Community input is needed on each of these issues, which must be addressed simultaneously. There is a need for clear leadership to execute such a coordinated, comprehensive agenda. Advocates must hold donors, research entities and government leaders accountable for action both in South Africa, where CAPRISA 004 took place, and in every other setting where 1% tenofovir gel could potentially play a role as a new HIV prevention tool. The CAPRISA 004 data show the impact the gel could have in reducing women's risk of infection via vaginal sex. Additional information is needed on safety and effectiveness of the gel among populations such as adolescents, pregnant women and others. There is also a need to continue evaluation of 1% tenofovir gel for anal sex.