Even without a cure, the end of the AIDS pandemic is in sight

A very bold statement to make in the run up to AIDS 2012, none the less, this is the view of Dr. Anthony Fauci, director of the National Institute of Allergy and Infections Diseases (NIAID )

NIAID director Dr. Anthony Fauci addressing the United Nations General Assembly special session on HIV/AIDS on 10June 2008.

Dr. Fauci was appointed Director of NIAID in 1984. He oversees an extensive research portfolio of basic and applied research to prevent, diagnose, and treat infectious diseases such as HIV/AIDS and other sexually transmitted infections, influenza, tuberculosis, malaria and illness from potential agents of bioterrorism. NIAID also supports research on transplantation and immune-related illnesses, including autoimmune disorders, asthma and allergies.  Dr. Fauci serves as one of the key advisors to the White House and Department of Health and Human Services on global AIDS issues, and on initiatives to bolster medical and public health preparedness against emerging infectious disease threats such as pandemic influenza.

Dr. Fauci has made many contributions to basic and clinical research on the pathogenesis and treatment of immune-mediated and infectious diseases. He has pioneered the field of human immunoregulation by making a number of basic scientific observations that serve as the basis for current understanding of the regulation of the human immune response. In addition, Dr. Fauci is widely recognized for delineating the precise mechanisms whereby immunosuppressive agents modulate the human immune response. He has developed effective therapies for formerly fatal inflammatory and immune-mediated diseases such as polyarteritis nodosa, Wegener’s granulomatosis, and lymphomatoid granulomatosis. A 1985 Stanford University Arthritis Center Survey of the American Rheumatism Association membership ranked the work of Dr. Fauci on the treatment of polyarteritis nodosa and Wegener’s granulomatosis as one of the most important advances in patient management in rheumatology over the previous 20 years.

AN END TO NEW INFECTIONS?

Three decades into the AIDS pandemic an end to new infections is in sight, according to Dr. Fauci.

“We don’t even know if a cure is possible. What we know is it is possible that we can end this pandemic even without a cure,”

Fauci told AFP in an interview ahead of the International AIDS conference 22nd -27th July in Washington DC, America.

Some 34 million people around the world are living with human immunodeficiency virus, which has killed 25 million since it first emerged in the 1980s.

The theme of this conference, which is held every two years, is “Turning the Tide Together,” and is based on experts sharing knowledge of the latest advances and how to best implement them in order to halt new cases of HIV/AIDS.

“We have good and effective treatments but we have to keep people on the treatments indefinitely in order to keep them well,” said Dr. Fauci, referring to antiretroviral drugs which have transformed a deadly disease into a manageable condition.

“When you have a very marked diminution of the number of new infections then you reach what we call and AIDS-free generation.”

Dr. Fauci said he did not expect any staggering breakthroughs to be announced at the conference, but that the gain would come though collaborating on ideas to speed progress by using the tools that practitioners have already at hand.

Otherwise, if progress continues at the present rate of reducing new infections worldwide by about 1.5 percent per year, the goal becomes too distant, he said.

Recent studies that tested antiretroviral drugs in healthy people as a way to prevent getting HIV through sex with infected partners have shown some promise, though getting people to take their medication daily had proven a challenge.

“The important thing is you have to take your medication,” Fauci said, noting that average HIV risk reduction in a study of men who have sex with men was just 44 percent.

The approach of treating healthy people with antiretrovirals is known as pre-exposure prophylaxis, and “is not for everyone,” Fauci said. “We have to selectively use it.”

The US Food and Drug Administration on Monday approved the first pill for HIV prevention, Truvada, despite concerns by some in the health care community that it could encourage drug resistance and risky sex.

Novel ways to boost testing are also good news, particularly with the recent US approval of the first at-home HIV test.

“It is so important in the quest to ending the AIDS pandemic to get as many people tested as possible. You can link them to care and get them on treatment. Anything that makes that goal easier would be an important advance.”

As far as an AIDS vaccine, Fauci said researchers have made “good progress” but “still have a long way to go.”

Experts are examining a trial done in Thailand that showed in 2009 modest efficacy of just over 30 percent, but is still considered a breakthrough and offers clues for future study into why some were helped and others were not.

Dr. Fauci also said he did not expect much concern to be raised over upcoming reports of the extent of drug resistance to antiretrovirals.

“People may think I am taking it lightly but quite frankly it is not a serious problem,” Fauci said.

He added that overall, AIDS research is “going well” even though “funding is restricted right now.”

And he expressed pride in the United States’ President’s Emergency Plan for AIDS Relief (PEPFAR), “which has really transformed how you can get people in low income countries to get on treatment care and prevention.”

The United States provides almost half the world’s funding for international HIV assistance, according to UNAIDS.

The International AIDS Conference is returning to the United States after more than two decades away due to a ban on travel and immigration by people with HIV that was lifted in 2008 and signed into law in 2009.

Fauci called those restrictive laws “unfortunate” and “embarrassing.”

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• HIV-prevention drug Truvada approved by US (lass.org.uk)

Will we ever have an HIV vaccine?

For around 30 years we have lived under the spectre of HIV. In the early 1980s, the mysterious appearance of symptoms that would later be known as AIDS led to unprecedented efforts to unmask the cause. On 23 April 1984, Margaret Heckler, the US Secretary of Health and Human Services, told the world that scientists had identified the virus that was the probable cause of AIDS. She was correct. She also said that a vaccine would be “ready for testing in approximately two years.” She was wrong.

Images by Wellcome Images/Flickr.

Despite 28 years of research, there is still no vaccine that provides effective protection against HIV, and in that time around 25 million people have died of HIV-related causes. To understand why creating a vaccine is so hard, you need to understand HIV. This is no ordinary virus. Scientists who study it speak of it with a mix of weary frustration and awed reverence.

The virus is the most diverse we know of. It mutates so rapidly that people might carry millions of different versions of it, just months after becoming infected. HIV’s constantly changing form makes it unlike any viral foe we have tried to thwart with a vaccine. “Almost every vaccine that’s been developed protects against a small number of strains,” says Gary Nabel, Director of the Vaccine Research Center at the US National Institute of Allergy and Infectious Diseases (NIAID).

Vaccines train the immune system to recognise part of a virus, creating a long-term armada of antibodies that seek and destroy the invader, should it ever show its face. For HIV, the most obvious target is gp120, the surface protein that it uses to attach itself to human cells. But gp120 also constantly changes shape, making it difficult to recognise. It also comes in clusters of three that are shielded by bulky sugar molecules, hiding it from the immune system.

On top of that, HIV targets immune cells, the very agents that are meant to kill it. And it can hide for years by shoving its DNA into that of its host, creating a long-term reservoir of potential infection.

So, creating an HIV vaccine is like trying to fire a gun at millions of shielded, moving targets. Oh, and they can eat your bullets.

Uphill struggle

So far, nature has provided little reassurance that a vaccine against HIV is even possible. For virtually every other microbe, there are people who naturally recover from their infections. “Nature itself provides the proof-of-concept experiment. It has told you that the body can inherently do this,” says Anthony Fauci, an immunologist who heads NIAID. But when it comes to HIV, “we have the astounding reality that, with more than 30 million people living with the virus, there is not a single documented case of someone mounting an immune response to completely eliminate the virus from their body.” Some people have the right genetic qualities to keep the virus in check, but no one clears it.

Given these challenges, it should be no surprise that vaccine research has been, to quote one researcher, a “Sisyphean onslaught of disappointments“. Only three potential candidates have made it through clinical trials. Vaxgen’s AIDSVAX vaccine, consisting of two fragments of the gp120, failed to provide any protection. Merck’s v520 vaccine, consisting of a harmless cold virus carrying three HIV genes, fared even worse. It was meant to marshall immune cells called T-cells to kill off infected cells. It failed. Worse still, the trial had to be stopped early because vaccinated people seemed to be more susceptible to infections, for reasons we still do not fully understand.

The only sliver of success came in 2009. A Thai trial of more than 16,000 people – the largest one yet – had been testing a combination of two vaccines: a bird virus containing three HIV genes, which was meant to prime the immune system, and a tweaked version of the AIDSVAX vaccine to act as a booster. Since both vaccines had failed individually, critics argued that the trial was a waste of time and money. But to many people’s surprise, the combination reduced the risk of infection by 31% – a statistically significant effect, though too low for a useable vaccine. (For comparison, the measles and polio vaccines are around 95% effective).

Some scientists were sceptical about the results, noting that the protection was short-lived and confined to people at low risk of infection. Others saw a ray of hope after years of frustration, a sign that a vaccine is in principle possible. Either way, the trial was confusing, especially since the vaccines did not reduce the levels of virus in infected people. Scientists are still trying to work out why the vaccine had any effect at all.

Renewed hope

But despite the muted results from existing trials, scientists in the field are unfazed. The reason, according to Wayne Koff from the International AIDS Vaccine Initiative, is that since the Thai results were announced, “the field that has begun to undergo a renaissance.”

It turns out that many HIV patients carry secret weapons – “broadly neutralising antibodies” – that can attack a wide range of HIV viruses. For these patients, it is too late. Their infections are already in full swing and the virus can mutate around their defences. But the discovery proved that HIV’s vaunted diversity is not the roadblock for vaccines that many scientists feared. If we taught the immune system to make these antibodies early, we could destroy the virus before it gained a foothold.

It is possible to isolate the right antibodies because we now know the shape of HIV’s surface proteins, down to the atomic level. Nabel used this knowledge to identify parts that stay the same while the rest of the virus shifts and mutates. These non-mutating regions are likely to be vital areas that cannot change without causing problems. He searched patients’ blood to find antibodies that target these conserved regions, and cells that make those antibodies. In 2010, he found three: two of which could neutralise 90% of HIV viruses. Other scientists, such as Dennis Burton of the Scripps Research Institute, have made similar discoveries using similar methods.

Nabel’s vision is a cocktail of these super-antibodies that target different parts of the virus, cutting off its evolutionary escape routes. He hopes to start clinical trials of his first-generation antibodies by early 2013, and he says is close to producing a second-generation of even heavier hitters that he thinks are two to three years away from early trials.

Vaccine researchers are also working on ways of stimulating our T-cells to kill infected cells at an early stage. This was the strategy behind Merck’s failed v520 vaccine, but scientists have since found better ways of smuggling viral genes into cells, and targeting them at the tissues most likely to be infected first. Both approaches would be complementary: “I think we would need a combination of broadly neutralising antibodies and a broad and robust T-cell response,” says Koff.

Compelling need

There is no telling when, or indeed if, these strategies will yield results, but what is certain is that the need for a vaccine will not diminish. There are many ways of preventing HIV infection, including condoms, microbe-killing gels, and the use of treatments as soon as people get infected. “We’d be going in the right direction with the tools we already have,” says Fauci. “But if we added a vaccine to the toolkit, even if it wasn’t 90% effective, you could have a major additive effect. There really is a compelling need for one.”

It may seem frustrating that decades of research have yielded nothing that satisfies this compelling need. But everything in the pipeline has depended on a steadily accumulating knowledge of the virus over those years. And as much as we know about the virus, and our immune response to it, there is still a great deal to learn. Also consider this. It took 47 years to create a vaccine for polio after the microbe behind it was identified. The measles vaccine took 42 years. The hepatitis B vaccine was a positive sprint at 16 years. “Twenty-eight years isn’t an inordinate amount of time,” says Fauci.

via: http://io9.com/5910946/will-we-ever-have-an-hiv-vaccine

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