2010 will be a year to remember for the field of HIV prevention. After decades of interventions with limited results (with the exception of circumcision and the prevention of mother to child HIV transmission), two clinical studies are raising the hope that the HIV epidemic can be tamed.

In July, the CAPRISA team (based in South Africa) reported that a vaginal gel containing the anti HIV drug tenofovir could reduce the risk of HIV infection by 39%. This was the first proof of concept that a microbicide could potentially reduce the risk of HIV infection whilst offering women an HIV prevention tool that they could control.

In November of the same year, the iPrEx study conducted on a population at high-risk of infection showed that taking the anti HIV Drug Truvada reduced the risk of contracting the virus by an average of 44 percent.

Both studies are hailed as a milestone and landmark in the history of HIV prevention and expectations are high that HIV prevention will finally mean more than the ABC of ‘Abstinence, condom and faithfulness’. But despite the hope, neither approach will immediately translate into marketable products as there are a number of questions that needs answering before microbicide and PrEP are available to the public.

Can a pill a day prevent HIV?

The iPrEx study was a large clinical trial, sponsored by the US-National Institutes of Health (NIH) with co-funding from the Bill and Melinda Gates Foundation and drugs donated by Gilead Sciences. Its purpose was to test if taking two anti-HIV drugs on a daily basis could help prevent HIV infection amongst HIV negative people at high risk. The approach called Pre-Exposure Prophylaxis (PrEP) is based on the concept that drugs are taken to prevent infection rather than treat it. This is similar to taking anti-malarial tablets when travelling in areas where the disease is endemic. The study was conducted in the USA, South Africa, Ecuador, Peru, Brazil and Thailand and involved 2,499 sexually active Men who have Sex with Men (MSM). The drug tested, Truvada (a cocktail of two drugs), is commonly used to treat people infected with HIV.

The study, published in the New England Journal of Medicine, showed 44% less HIV infections in the group that was given the drug compared to the group that received a placebo. These results represent a significant development in the field of HIV prevention. However, they cannot easily be translated to other groups ‘at risk’ or to the general population without further studies.

Whilst the PrEP approach raises hope for the prevention of HIV infection, it also presents a number of challenges for scientist, advocates, and crucially for public health systems. Many of these challenges, such as adherence (people taking their pill as prescribed), side effects, potential resistance (existing drugs becoming ineffective against the HIV), and cost effectiveness are best left for discussion by scientists and clinicians as they will require many more clinical studies.

In the meantime, the PrEP approach raises more pressing ethical and social concerns for public health.

PrEP can only be used by people who know they are not infected with HIV. Hence, those who want to access PrEP need to take an HIV test, not once, but at regular intervals. How often is not known yet, but every 3 or 6 months seems reasonable. Getting people to test once is not always easy for a number of reasons. Getting people to test regularly will be even more difficult (and costly), but not impossible if testing becomes part of routine health checks (a controversial issue in itself).

However, regular testing will lead to the identification of existing infections that in turn will require immediate treatment (in the US and the UK about half of those testing positive for HIV need to start treatment at the time of the diagnosis). As PrEP is rolled out, more people in need of ARV will be identified, and inevitably there will be a competition for resources between the sick and the healthy.

Providing ARV treatment to those who need it is already putting a huge strain on the health system of many countries in both the developing and developed world. Considering that only a third of those in need of treatment are currently receiving it under the new WHO guideline, prioritizing a potential PrEP roll out would be an inevitable necessity.

Prioritising PrEP?

Could PrEP potentially be a useful option in some circumstances for some people, particularly for those populations called most at risk populations (MARPs)?

MARP is a broad acronym including Men who have Sex with Men (MSM), Sex workers (males and female, commercial or not), injecting drug Users (IDUs), and any population that has more risks of being infected by HIV than the general population. However, the concept of population ‘at risk’ or ‘vulnerable’ is a controversial and contested one. Not all MSM are ‘at-risk’, a large number of them actually use condoms regularly and consistently. Studies have even shown that gay men were often infected by their partner with whom they were in a stable relationship. Likewise, condom use amongst commercial sex workers can be high (for example it is over 90% in brothel-based sex workers in Cambodia), with many patrons using condoms with a sex worker but not with their regular sex partner. Hence it is not ‘Populations’ that need to be identified and reached, but individuals within these populations and this will be a serious problem if PrEP is prioritized.

Besides, the general population cannot be ignored, particularly in Sub Saharan Africa, home of 68% of all people living with HIV. The UNAIDS 2010 AIDS epidemic update observed that data from urban Zambia “suggest that 60% of the people newly infected through heterosexual transmission are infected within marriage or cohabitation , compared with more than half in Swaziland, 35%–62% in Lesotho and an estimated 44% in Kenya”. . A similar proportion of new infections occur among steady, long-term heterosexual partners all over sub-Saharan Africa suggesting that heterosexual and in particular young girls aged 19-24 could be the primary target for PrEP if it has to be prioritised to the most at risk.

In the current context where for every 2 people put on treatment, 5 become infected, suggesting putting millions of healthy people on treatment, some of them potentially at an early age, when so many who are in need of it can’t access it, is surely asking for trouble.

Taking a pill a day to avoid taking a pill a day?

Should PrEP be proposed to at-risk individuals as an HIV prevention option alongside other non medical approaches? There are still a number of clinical studies to conduct before PrEP is made available to the public. But in some cases PrEP could be detrimental to its intended recipients. For sex workers, the introduction of PrEP could mean replacing a highly effective HIV prevention method (condom) by a less effective one. PrEP is also expensive and will not protect against other STIs. It does not have contraceptive property and could put sex workers back under the control of customers who will be able to enforce sex without condom. For IDU, it would be replacing a non-medical approach that we know works: needles-exchange programmes. And when the acceptability of treatment for those sick with HIV is an issue, will healthy individuals even if at risk be willing to take a pill regularly?

Remarkably, most of those who are at higher risk of being infected with HIV are also those that governments are less prepared or likely to invest resources in. Health care for junkies, prostitutes and gay men rarely score high on the political agenda, and electoral pledges centred on the health of these groups wouldn’t attract many of the electorate.

It would be dangerous to ignore or disregard the impact PrEP could have on a national health system with the risk of introducing two tier/two waiting rooms health care. There will be those who can afford PrEP whilst others will still be on waiting list to receive anti-HIV medication (many already are, even in a developed country). The emergence of a black market in anti-retroviral drugs (ARV) and the spectre of counterfeits flooding it, should not be disregarded, particularly in the developing world where the most vulnerable could easily fell prey to ‘ARV drug dealers’.

To date, having failed to achieve the sustained change in behaviour required to reduce the number of new HIV infections at the population level, making little progress in getting rid of discriminative laws that stigmatise and cast out those most vulnerable (76 countries have state-sponsored homophobic laws), and facing the challenge of achieving universal access to HIV treatment by 2015 (MDG 6) should we now embark on this controversial approach to HIV Prevention?

The iPrEx Team deserves praise for the quality of their work and should be commended for providing the first proof that daily oral use of an anti-HIV drug can reduce the risk of HIV infection This is an important breakthrough for HIV prevention. It has been a long road pockmarked with ambushes and difficulties. But now, Pandora’s Box is open at a time when his holiness Benedict XVI is opening even ever so slightly the  door to condom use, at a time when the World Health Report 2010 confirms that one billion people cannot afford healthcare and at a time when the latest UNAIDS AIDS 2010 epidemic update shows that the rate of new HIV infection is stabilising at around 2.6 million new infections a year.

No matter how one looks at it, the iPrEx study has opened the door to the medicalisation of sex, and in the current state of research and prevention, that amounts to taking a pill a day to avoid having to take a pill a day.

The views expressed in this article are the author’s and do not necessarily reflect the views of his employer or of the organisations he works for.

Originally published by openDemocracy on 25 November 2010

This review considers the use of antiretroviral drugs specifically to prevent HIV transmission. Antiretroviral therapy (ART) can be implemented for the protection of uninfected individuals both before (preexposure prophylaxis) and after (postexposure prophylaxis) exposure to HIV infection. Preexposure prophylaxis may be used coitally dependently when individuals are intermittently exposed or by continuous daily dosing for those constantly exposed; postexposure prophylaxis is used in 28-day courses. Alternatively, ART can be used strategically to reduce the viral load and consequent infectiousness of an HIV-infected individual, thereby limiting the risk of onward viral transmission. A policy of universal HIV testing to enhance the identification of all HIV-positive individuals followed by immediate treatment of all HIV-positive individuals, irrespective of their CD4 cell counts (universal test and treat), has been postulated as a potential tool capable of reducing HIV incidence at a population level. This concept represents a paradigm shift in the use of ART, targeting infectious individuals for prevention rather than protecting uninfected exposed populations. This strategy could have the advantage of preventing transmission and reducing HIV incidence at a population level, as well as delivering universal access to therapy for all people living with HIV and AIDS, potentially eliminating mother-to-child HIV transmission and limiting concomitant diseases such as tuberculosis. This review critically examines the scientific basis of ART for HIV prevention, summarizing the risks and opportunities of the potential expansion of ART for prevention. Specifically, we consider the evidences for and against targeting HIV-uninfected individuals compared with enhanced HIV testing and treatment of HIV-infected individuals in terms of impact on viral transmission.?

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2010 will be remembered as the year when the results of the CAPRISA trial that followed those of the Thai vaccine trial in 2009 reshaped the biomedical approach to HIV prevention. These are also the years in which HIV prevention has been both at a turning point and in turmoil with repeated assaults on populations at risk, notably in countries with high HIV prevalence and an economic crisis rewriting the funding agenda. Further trials of new prevention technologies (such as Pre-Exposure Prophylaxis) and a recognition that treatment can contribute to prevention, all happening against a background of economic recession are creating confusion and dilemmas amongst advocates, funders and beneficiaries as to what should be done next to successfully contain and quell the HIV epidemic.

The tenofovir-based microbicide tested in the CAPRISA trial is an obvious way forward but it is widely acknowledged that more trials are needed to confirm the study’s results and to ensure that the effect observed in this one trial can be confirmed in different settings and countries and to assess easier ways to use the product. If confirmed, this microbicide would be the first women-controlled HIV prevention tool.

But this is where promising clinical science has hit a snag. A number of trials have been in the planning pipeline for some time already, even before the results of the CAPRISA study were known. All have the potential to provide critical information about the product acceptability, use and effectiveness, information that is necessary to license the product. But less than 40% of the money needed (about USD 150 million) to conduct these trials has been committed or pledged by donors.

This is neither satisfactory nor acceptable. Insufficient funding could not only limit and slow down the development of the product, but it also leaves scientific decisions at the mercy of economics rather than hard scientific evidences. And haven’t we been told enough that scientific and clinical research should be evidences-based?

Whilst INGOs, donors, politicians, and philanthropists are being cajoled into supporting these much needed studies with money that is mostly ours, more than 7,000 new infections are occurring every day, a large majority of them in Sub-Saharan Africa, disproportionately affecting women whose urgent need for an HIV prevention tool they can control could be fulfilled with an efficient tenofovir-based microbicide.

In addition, the reticence towards identifying and committing funds to cover the necessary studies places scientists in a position where they have to support one study rather than another because funding is limited and investments need to be prioritised in times of global recession and a massive bank bailout. The message is clear: there is no money for HIV, only for bankers, as only they can help the economic recovery.

The irony is that a small investment in the tenofovir trials could make a huge and rapid economic difference. Many scientists, NGOs and activists (with some exceptions) have bought into the argument that there is not enough money to adequately address the HIV epidemic and are prepared to compromise on the science fearing that raising concerns or calling for more support may jeopardise the little money available.

As a scientist, activist, advocate, and an individual directly affected by the HIV epidemic, I can’t accept giving up or caving in to the general apathy, resignation and funder’s whim. The HIV epidemic can be dramatically curbed within a few years if we decide to give priority to prevention and match funding and policy accordingly. Letting ourselves be led by economic interests or twisting science’s arm will not buy us out of the epidemic.

Published on openDemocracy on 25 October 2010

Some object that quantity does not equate quality; however, content is not the only challenge the UK science base is facing. Science faces a continuum of challenges from school to university, from university to the public world. It is a challenge to teach and train people in science but also to publicise and exploit, commercially or not, the results of scientific research. In this article, I will introduce 5 major challenges that should inform education and science policies.

The first challenge: changing the image of science in the public and the scientific community.

Science does not have a good public image, particularly in the media. When it is not “mad” scientists developing Frankenfood or carelessly releasing food and mouth virus into the English countryside, we are inflicted with TV-boffins trivialising science.

It results that the public lack confidence in science (MMR) or engineering (nanotechnologies), does not understand what science is about or what scientists do and can’t judge if science is good or bad. Often in this situation, bad prevails. We know the problem stems from scientists being bad communicators but also that the public has received little science education. It is right to complain of the lack of science teachers or of the declining number of students taking science A-level, but let it be clear, for many young people a career in science does not sound a good career move. Studies are long, difficult, career prospects are uncertain and wages are not very good.

But science image-problem goes beyond the public and is manifest within the scientific community, where it originates as revealed by a report from the Council for Science and Technology in a recent report. Forsaken PhD students, badly managed Post-docs and scientists fed up that science is not at the heart of what they are doing, contribute to the feeling that the pain is not worth the game.

The situation could be improved by tackling the second major challenged faced by science, that of improving science administration and management.

Scientists are professional people trained in science, but they are often unaware of basic administration and management skills that they will need in their career. This is a problem because grants need to be administered, projects need to be managed, and crucially people need to be managed and mentored. Too often Ph.D. students are left on their own, post doctoral fellows do not get the professional support they need, and researchers spend more time doing paperwork and politics than research. The result is a waste of time and resources.

Resources and in particular funding could be a challenge in itself, but because it is a pervasive issue, I’ll only underline the commercialisation of science and the funding priorities. It is nowadays common for senior scientists to be involved in a biotech company. Public/Private partnerships are becoming a necessity because research is costly and also because there is a political will to develop these collaborations. Such ventures influence the direction scientific research is taking as well as how it is administered and managed. It is important to ensure that the private sector does not dictate what science should be about as it is also important for research councils not to constrain research to what they are willing to fund.

If administration and management are new essential skills needed by scientists, they also need more scientific skills. Science has benefited for fast engineering development leading to the next challenge which, to borrow from Thomas Homer Dixon who wrote extensively about it, is the Ingenuity Gap challenge.

Dixon describes a world where complexity increases very quickly but where our ability to manage and comprehend it does not follow as quickly, hence an “ingenuity gap”. During the last 30 years, science had made tremendous technical progresses allowing us to do research at a very different scale. There are two major problems with the speed and breadth of these developments.

First the data collected can be so vast or so new (such as generated by genomic or metabonomic study) that scientists don’t always know how to handle them. Often people do not have the skills needed, in particular statistical skills, to analyse the data and new mathematical model need to be developed before sense can be make out of numbers. More often, the problem is that of 21st century science analysed with a 20th century mindset and of the nature and immensity of data confronting our inability to fathom it.

Second, these methodologies and equipment require specialist technicians to handle them, but technicians are not common in science; university does not produce them. Post doctoral fellow can be reluctant to accept a position where they will have limited input in the scientific work and little prospect for first author publication that they would need to progress in their career.

But the problem of analytical skills goes far beyond analysing complex data. There is a general problem of numeracy and literacy amongst the population that also affect science students and that seriously challenge their future ability to do research.

Unfortunately, this increased complexity is not happening in isolation but in a wider context leading to the next challenge, that of the globalisation of science.

5% of the world research is done in the UK. Students come from all over the world to study here, the UK counts four universities in the top 25 world universities.

But this should not hide the fact that less than 30% of the post graduates comes from the UK, that China is producing 2 millions graduates a year, that South Korea’s R&D public budget will match that of the UK this year and that the situation worldwide is changing. The report from the HEPI indicates that some foreign students are not satisfied with the value they get for their money and that they now prefer to go to the US where there are more facilities and more scholarships.

Foreign students do not only contribute financially to UK science by paying heavy university fees, but they also sustain UK science. The truth is not that the UK cannot deliver good science but that other countries are able to do so and not only the US.

The challenge of globalisation also impacts on the scientist ability to conduct their work. The recent outburst from Lord Winston who was denied the possibility to carry on with a research work on humanised pig and decided to move this research to the US is an example of how red tape and policy can be an obstacle to research in the UK. Withholding judgement, this highlights a need to review processes and policies.

Falling standard, inadequate training, worldwide competition, and a bad press, is UK public science doomed? That would be painting too much a dark picture of a still thriving sector. The last challenge may give a new direction and provide innovative and relevant answers.

Mainstreaming science and empowering scientists

Although students and scientists organisations and Trade Unions have made impressive achievements, the policy-making process seems often in the hand of distant policy makers and the scientific establishment. It is fundamental to engage more students and scientists into the governance and political process and to value their day-to-day experience of science when drawing new policies. It is also important for these organisations to be representative of their base. And move the process “closer to the bench”.

Moreover, because so many aspects of our life today are connected to scientific or engineering issues, from health to personal freedom, mainstreaming science is a necessity. Science can not anymore be considered the exclusive domain of the white-coat-clad scientist who knows better. The challenge is to bring scientists and their science out into the public domain and into the political process and to make scientists the agents of science policy.

There is a long journey ahead to make science more relevant for public policies, less nebulous in the public eye and more considerate for science students and academics. But scientists are overall passionate people and it is possible to channel some of this passion into the social and political process.

© Roger TATOUD.

Project Summary: curation of the IRS/PKB cascade of events (6 months).

Role: Supervision and contribution to the work.

The information in the Reactome database is authored by biological researchers with expertise in their fields, maintained by the Reactome editorial staff, and cross-referenced with PubMed, GO, and the sequence databases at NCBI, Ensembl and UniProt. In addition to curated human events, inferred orthologous events in 21 non-human species including mouse, rat, chicken, fugu fish, worms, fly, yeast and E.coli are also available.

This work involved:

• researching the literature
• summarising the published knowledge in a synthetic format
• training and directing the work of a student

The results of this project is now available online to the scientific community.