Researchers Look to Pill, Taken Daily, to Avert H.I.V.

By LAWRENCE K. ALTMAN
Published: August 4, 2008
New York Times

MEXICO CITY — Can a pill a day help prevent infection from H.I.V., the virus that causes AIDS?

No one knows. But researchers in a number of countries are conducting trials and planning others to test the unproven strategy that a daily pill, or a combination of drugs, can prevent H.I.V.

By mid-2009, more people will be enrolled in such trials than in all of those for H.I.V. vaccines and microbicides, the AIDS Vaccine Advocacy Coalition said in a report issued here on Sunday at the start of the 17th International AIDS Conference.

Initial findings of the safety and effectiveness might come early next year, although researchers do not know how they will compare to the disappointing results of recent tests of H.I.V. vaccines and microbicides, chemicals that women can put in their vagina to prevent H.I.V. infection.

In the face of those bleak findings, some AIDS experts say testing the prophylactic use of antiretroviral drugs, called PrEP, for pre-exposure prophylaxis, is now the most promising research in H.I.V. prevention efforts as scientific investigation of vaccines and microbicides continues.

The Centers for Disease Control and Prevention, which released a report on Saturday showing that the number of people newly infected with H.I.V. in the United States in recent years was 40 percent higher than has long been reported, said that PrEP was among the strategies that needed to be developed to substantially reduce the incidence of H.I.V. An estimated 2.7 million people become infected each year worldwide.

“We cannot wait for the study results to begin to prepare for the optimal use and delivery of PrEP,” said Pedro Goicochea, an investigator in a PrEP study under way in Peru and Ecuador. “Instead, we should look ahead to consider all of the possible outcomes of these trials and make real plans for making PrEP available to those who can benefit from it, as quickly and safely as possible if it is proven effective.”

The United States Agency for International Development, the C.D.C. and the National Institutes of Health are paying in part for all of the trials. The Bill & Melinda Gates Foundation is paying for part of two. The organizations have undertaken the trials because of the success in giving antiretroviral drugs to pregnant women to prevent H.I.V. infection in their infants and drugs to prevent malaria.

In 2007, Family Health International completed a similar study of the antiretroviral drug tenofovir for H.I.V. prevention among young women in Ghana, providing the first data showing such use was both safe and acceptable among uninfected users. But the study did not indicate if PrEP was effective in preventing new infections.

Studies in a small number of nonhuman primates hint that PrEP can reduce the risk of infection of a simian form of H.I.V. in nonhuman primates.

Initial PrEP studies are testing tenofovir, either alone or combined with another drug, emtricitabine.

Infected people taking these licensed drugs have shown limited side effects like nausea, vomiting, diarrhea and intestinal gas. But the safety of the drugs must be established among noninfected people as well as among participants who become infected in the study.

Trial participants include gay and bisexual men, heterosexual men and women, couples in which one partner is H.I.V. infected, and sex workers.

Up to 15,000 people are expected to be participating in trials by mid-2009. Sites of the trials include Botswana, Brazil, Ecuador, Kenya, Malawi, Peru, South Africa, Tanzania, Thailand, Uganda and the United States.

Male circumcision has proved effective in a significant percentage of H.I.V.-negative people in trials in Africa.

Because PrEP might also work in a significant percentage of uninfected users, the advocacy coalition and other researchers say now is the time for governments, health officials, donors, researchers and advocates for AIDS research to prepare for the maximum public health benefit if the pill-a-day strategy works.

One reason for the immediacy, they say, is that even if a PrEP strategy proved successful, it would not be a silver bullet. PrEP would need to be combined with standard prevention measures like safer sex practices, use of condoms and clean needles, and counseling.

Governments would need to prepare for global procurement of PrEP, arrange adequate staffing to deliver the drugs and provide counseling and determine who will pay for the costs, said the coalition, which describes itself as an international nonprofit, community- and consumer-based organization.

Provisions would also need to be made for participants who do become infected, and findings from a number of trials would be needed before PrEP could be widely recommended.

Results may be hard to interpret because the tests are being conducted in different ways and so may produce varying findings, the advocacy coalition’s report said. Statisticians could face challenges in pooling the data from the trials.

The report also said that the initial findings were likely to raise questions needing further study, like whether taking pills intermittently — like just before a sexual act — can be effective. The report is available online at www.avac.org/prep08.pdf.

Researchers conducting the studies said they were taking longer than initially expected. Among the problems are recruiting volunteers and addressing the real or perceived stigmatization of those who participate.

Bermuda Should Become an Example for Other Island Nations...

SAVING THE PLANET Bermuda should be a role model for other island nations

Dr. Anthony Knap pictured outside BIOS at Ferry Reach, St. George's.
Photo: Akil Simmons
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By Amanda Dale

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Bermuda should become a role model for other island nations by harnessing the power of the sun and oceans, according to a leading scientist.

Dr. Anthony Knap, President and Director of the Bermuda Institute of Ocean Sciences (BIOS), says even the algae in our waters could be transformed into biofuel (fuel derived from dead biological material). The Island should also explore the feasibility of nuclear power such as a Generation IV pebble bed reactor, in its quest to find alternatives to fossil fuels.

BIOS is at the forefront of global research into climate change, with the longest running time series into ocean acidification (Hydrostation S and the Bermuda Atlantic Time-series). It is now to take part in a joint project with the Bermuda National Trust, mapping sea level rise to determine the repercussions on Bermuda. Dr. Knap explains...

The ice caps are melting, animal and plant species are dying out, and disease epidemics could threaten our very survival.

The Earth's over-population and over-consumption is resulting in pollution, habitat loss, and the destruction of marine and terrestrial eco-systems. The impact of global warming meanwhile, is expected to bring rising sea levels, stronger hurricanes and coastal flooding, with droughts, forest fires and heatwaves in more arid parts of the world.

Even if humans stopped burning fossil fuels such as oil and coal tomorrow, scientists say there are already enough heat-trapping greenhouse gases in the Earth's atmosphere to cause temperatures to increase and sea levels to rise for another 100 years. The Intergovernmental Panel on Climate Change (IPCC) predicts global temperature rises of between 1.4 and 5.8 degrees Celsius by 2100. Its 'Low Emissions Scenarios' for sea level rise meanwhile, are between 9 - 48 cm by the 2080's, with 'High Emissions Scenarios' predicting 16 - 69 cm.

Distinguished conservationist Dr. Richard Leakey has also warned that the world is heading for its sixth period of mass extinction. Dr. Leakey says Earth is losing 50,000 - 100,000 species every year – a rate of extinction which could tip our fragile eco-balance. He warns that unless the trend is reversed, the world could lose about 55 percent of its species in the next 50-100 years.



Here in Bermuda our over-reliance on fossil fuels is also a costly business. It is therefore vital that the community gets involved in Government's search for alternatives in the National Energy Policy initiative. By reducing our carbon dioxide emissions, adopting new technology and alternative fuels, and by becoming more environmentally-conscious consumers, we can all make a difference.

Dr. Anthony Knap, BIOS President and Director, says in 1954 the Island imported 90,000 barrels of oil at $2.89 a barrel. Now Bermuda imports a million barrels at $135 each.

"That's almost $140 million of fuel being burnt, so it's the issue for Bermuda," he says.

"I applaud the Ministry (of Energy) for trying to get a public debate going. It is important, because if we buy into these new technologies such as wind power it is going to affect the landscape, so it is within all of our interests. A big wind farm four miles off Bermuda however, could provide a huge amount of peak power.

"One of the big issues is can we conserve more? Can we be more efficient? Because every barrel we have to bring in is not good for us."

Dr. Knap says: "We've got an abundance of sunlight in Bermuda and ocean energy from waves. Just off the Island we also have ice cold water which we could bring up from the deep for use in air conditioning and so on.

"There is no reason why this Island couldn't be a blueprint for energy efficiency, and I believe the Ministry and Minster (Terry Lister) are taking this very seriously - as they should.

"Small islands around the world, nearly all of them rely on oil and have the same problem of one provider of electricity who has grown over time. They are all net exporters of carbon.

"I think it is very healthy now to have this debate in Bermuda, to address the issues."

Dr. Knap says the Island should explore the possibility of nuclear energy, such as a Generation IV pebble bed reactor, as has been adopted in South Africa and China.

"Whether a pebble bed reactor is right for Bermuda or not, who knows, but the Department of Energy and the Minister are trying to get an open debate on energy needs for the Island and plan for the future. Belco want more generators to meet demand but a lot of people don't want generators in their backyard. There are issues of conservation, because we are very energy intensive," he says.

"I'd like to see Bermuda become the model for island nations. We have a good economy here and so have the money to do things which other places don't.

"I think certainly we could develop new technologies and could lead the way in energy efficiency and in re-applying some of the things which are presently available."

Dr. Knap is also keen to see global taxes levied on CO2 consumption.

"Most businesses now have accepted the fact the climate is changing," says Dr. Knap. "Policy is being driven this way and now if you're in business and are not green, you're not going to get many customers.

"But I think a proper price has to be put on CO2. People can recycle but when you consider the massive energy needs of the planet, and the contamination that comes with that, if there is a tax on carbon then entrepreneurs, scientists and technical solutions will appear.

"My hope is that on a global basis there will be a price put on carbon that reflects the cost of either not putting it into the atmosphere or removing it, because right now it's a 700 billion ton a year problem. Right now, carbon is trading at about $25 a ton which is too cheap. It should be trading at about $100.

"James Lovelock (environmentalist/scientist/futurist and author of 'The Revenge of Gaia') is suggesting the level of CO2 in the atmosphere is 500ppm, and if he's right we are toast, because we will be there pretty quickly. He is calling for an immediate move to nuclear fuel. Of course, there's been this outcry that the father of the environmental movement has lost it, but frankly it's very practical."

Dr. Knap says: "The ocean is the largest repository of carbon. We need the oceans to mix more and the carbon to go into an ocean without acidifying it.

"The effect of climate change, with the increase of CO2 in the oceans, has a profound effect on carbonate ion which is what the corals use to grow. The average brain coral grows about 0.25 cm a year. Tidal rise at present is 3.2 cm a year so it is outstripping total growth of marine calcifying organisms like coral."

At BIOS, scientists Nick Bates, Ross Jones, Sam de Putron and Andreas Andersson have been working on the effects of calcification due to CO2 increase.

Dr. Knap says: "There are huge concerns, particularly in the Arctic right now, that this is changing the saturation state of carbonate, so there will be less available for organisms. There are concerns about food chain issues, such as mammals who eat clams. So it's a big problem.

"I give a talk that shows people how I became convinced global climate change was really happening, and it is the record going up in the oceans and in the atmosphere, and the increase of carbonate ion changing the alkalinity of the oceans.

"It's just like everything – a small amount makes a big difference. The pH of the oceans is about 8.1⅝.2 and if you go down to a little above 8 the whole calcification will shut off."

Coral growth and the ability of corals and other organisms such as mussels and clams to absorb carbonate, is one of the topics of BIOS's joint project with the Bermuda National Trust. Intern Amanda Baltimore, a Masters student with experience of Geographical Information Systems at the University of Toronto, will examine the prognosis of increasing CO2 in the oceans. She will also research storms and precipitation as well as mapping sea level rise and how that will impact the Island.

Dr. Knap says: "We are interested in framing global climate change and its effects on Bermuda.

"The idea is to determine at 10 cm intervals what the tidal rise would do to the Island, and how much land would disappear. The project is framing what the big issues are, such as more intense yet fewer tropical cyclones and how that will affect us.

"We know the climate is changing. If you look at scientific literature, no one has been able to suggest that something is not happening.

"With all this ice melting in the Arctic and massive changes in precipitation, the water vapour in the northern hemisphere has increased by four percent in the past 30 years, which means there is 20 percent more rainfall in major storms.

"And as the Earth has to balance its heat, as the tropics warm up there has to be a thermodynamic shift. The globe has two ways to do this. One is by the oceans, another is through the atmosphere.

"There are suggestions that the Arctic and Atlantic Ocean are fresher than they have ever been. There is therefore concern that this could cut off the heat conveyor belt and slow down ocean circulation. And if the ocean isn't going to move that heat then the atmosphere has to take it up.

"There are two ways to do that - one is with winter storms, the other is with hurricanes."

Dr. Knap adds: "The whole theory of increasing tropical cyclone intensity is due to the thickness of the thermocline. Isaac Ginnis of the University of Rhode Island has suggested that there is enough heat in a section of ocean 30km by 30km by 100m deep, with 30 degree Celsius water, to take any storm in the Gulf of Mexico to a Category Five.

"Our understanding of that heat flux is one of the things we're trying to do here at BIOS.

"We know more about the ocean by Bermuda than any other piece of ocean anywhere in the world. So whether it's the composition of the chemistry of the water or the biology, the microbiology or molecular biology, in all of our time series programmes there is a global interest in the data set that is generated by BIOS."

Dr. Knap joined BIOS as an Assistant Research Scientist in 1977 and became Director in 1986. He is an Honorary Professor at the University of Plymouth and an Adjunct Professor at the University of Delaware and NOVA University.

The oceanographer and Senior Scientist serves with many international organisations and is co-chair of the Coastal Ocean Observing Panel for GOOS (the Global Ocean Observing System). He has written more than 80 journal articles.

It is in the waters off Bermuda that a solution could be found to fossil fuels. Dr. Knap says that marine algae could become a "second generation" biofuel. He says the production of some biofuels such as ethanol has actually increased greenhouse gases.

"One of the problems with biodiesel at the present time is that it requires a huge amount of nitrogen," he says.

"With normal crops, you have to fertilise the fields using nitrogen as phosphorus fertiliser, and of course that oxidises the nitrous oxide and creates a greenhouse gas, so of course you've done nothing.

"Producers using food such as corn are also starving the Third World. Corn and wheat prices have gone through the roof, so we have to move very quickly from this first generation to the second in biofuel, and marine algae are certainly one way to go.

"We have organisms in the Sargasso Sea which require very little nitrogen and phosphorus. Algae have lipids in them, which is basically fat. There are extractors being built now which can release the cells and they are then hydrogenated to turn this into fuel."

It seems the solutions to Bermuda's energy crisis could be closer than we think.