Positive thinking winning HIV battle
Treatment for people with the AIDS virus is about to make its biggest leap in at least a decade. Science writer Leigh Dayton reports
HIV with the healing power of blood stem cells.
So far, the method involves removing HIV-infected stem cells from a patient’s bone marrow, growing new versions tweaked to fight HIV, and then returning the rejigged cells to the patient. ‘‘ As long as these cells persist in the patient we will have resistance to HIV infection, with the goal that there would be reduced viral load,’’ said Rossi, who believes the treatment could eventually be given as a shot or pill and combined with conventional treatment.Meanwhile, scientists such as Perth-based Simon Mallal are giving older drugs a new lease on life. On Wednesday he announced that by using high-tech DNA screening techniques, he and his colleagues at the new $20 million Institute for Immunology and Infectious Diseases, to be built at Murdoch University, have developed and trialled a test to determine if a patient will develop lifethreatening reactions to abacavir, a drug sold under the brand name Ziagen, and as combination pills that combine it with AZT or other drugs (one such combination pill being Trizivir).
‘‘ We’ve entered the era of personalised medicine,’’ says Mallal.
As Fauci’s long-lived patients attest, all these advances in HIV research are working. In fact, treatment is so successful that at the conference British expert Brian Gazzard raised a new conundrum facing HIV clinicians: geriatric AIDS.
According to Gazzard, chairman of the British HIV Association, it’s becoming clear that HIV infection increases the risk of suffering any of the geriatric giants’’: heart disease, dementia and cancers. What’s more, increasing numbers of people are becoming infected with HIV later in life.
Research has also revealed that HIV infection is the cause of serious organ damage that, until now, was blamed on the toxic effect of anti-retroviral cocktails. The finding has triggered a scientific rethink of when HIV people should begin drug therapy.
Usually, patients don’t start therapy until the level in their blood of a type of immune cell called CD4 cells drops below a certain point. Fauci says experts now want to conduct trials to test the emerging notion that earlier treatment is better.
He also wants more data on another treatment question: to treat or not to treat.
I’ve been convinced as the years go by that you many not necessarily treat someone who has a trivial level of virus and whose CD4 count is really very good,’’ he observes.
After all, a trivial’’ level of HIV is the goal of researchers struggling to design a vaccine against HIV. A vaccine, says John Kaldor, is the holy grail of HIV prevention.
From the very early days of HIV we’ve been hunting for a vaccine,’’ he says. But a vaccine is considered a huge (scientific) problem and will be one for a long time.’’
HIV laboratories around the world are humming. New discoveries and treatments are tumbling out of the research pipeline at a remarkable pace, one that promises HIV patients a longer, healthier life. This, for a disease that was a death sentence when it was first identified 26 years ago.
Little wonder that when nearly 6000 experts on HIV and AIDS from 133 nations gathered in Sydney this week for the fourth International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention, they buzzed.
‘‘ This is an enormously exciting time,’’ says John Kaldor, deputy director of the National Centre in HIV Epidemiology and Clinical Research at the University of NSW.
‘‘ Over the past two years people have made striking improvements in therapy, especially for people in whom several regimens have already failed. People have also made significant developments in what are considered biomedical tools — like microbicides — to help break the cycle of transmission.’’
Much, too, has been learned about how the insidious human immunodeficiency virus infects its victims, wreaks such damage and is so hard to beat. According to long-time HIVAIDS researcher Anthony Fauci, director of the US National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, new insights into the mechanisms by which HIV harms humans have underpinned development of over 25 anti-HIV drugs.
‘‘ These medications have had an enormous impact in reducing mortality wherever they have been used,’’ says Fauci who, as a clinically and scientifically trained infectious diseases and immunology specialist, was one of the first experts in the world to see, treat and attempt to unravel HIV infection.
‘‘ Patients I followed 25 years ago would die within months of getting seriously ill. Now I’m following patients for 10, 15 years. They’re doing just fine. The triumph has been great.’’
Entire new classes of drugs promise to keep the triumphs coming, particularly for patients who are developing resistance to the various combinations of existing drugs. To the outsider they sound baffling, but these classes — integrase inhibitors, fusion inhibitors, CCR5 antagonists and maturation inhibitors — promise to bring the biggest improvement in HIV treatment since the discovery in the mid-1990s that combined drug treatment, called Highly Active Anti-Retroviral Therapy (HAART), greatly improved viral suppression.
To get a feel for what such drugs are and do, it’s necessary to understand why HIV is such a knotty scientific problem. Firstly, as Fauci explains, it attacks the immune system: ‘‘ Virtually all of the viruses that have been scourges of mankind — or even viruses that have been trivial — are viruses that come in and affect the lung, or the skin, or the brain, or the gastrointestinal tract and the immune system is intact and is able to fight the particular virus,’’ he says.
Not so HIV. It targets the immune system itself, perversely destroying the very mechanism the body entrusts with its own defence. Moreover, it’s a retrovirus, a virus that has the ability to insert itself directly into its victim’s genetic material. It can hide out there. HIV also replicates quickly. That quick turnover enables the virus to mutate, to change its appearance so fast that even when it does stick its viral head over the parapet, the immune system cannot effectively respond.
It’s a triple whammy. HIV infects the immune system. It’s a retrovirus. It mutates rapidly. ‘‘ You put those three things together and you have a real problem,’’ Fauci concludes.
Still, researchers did target the culprit and have built weapons to fight it. The first antiHIV drug, AZT, was licensed in 1987, and works by inhibiting the HIV enzyme reverse transcriptase which the virus uses to convert its single strand of RNA into double-stranded DNA, a necessary first step prior to splicing itself into the host cell’s genome.
AZT was hailed as a wonder drug, but the euphoria soon faded when it became apparent that HIV’s high rate of mutation quickly allowed resistance to the drug to develop.
Later, other ‘‘ anti-retroviral’’ drugs were developed, and these are generally now combined into triple or even quadruple drug cocktails to prevent drug resistance developing. Among the most successful antiretrovirals now are Lamivudine, Viread and Ziagen.
US infectious diseases specialist Joseph Eron says the most exciting prospects among the new drugs about to become available are integrase inhibitors. These work by blocking another enzyme, integrase, which HIV uses to insert its genetic material into the host cell’s DNA. Two such drugs are in development and one, raltegravir, is already available on a trial basis in Australia.
More are on the way. Last week several biotech companies reported on laboratory, or early trials of even newer drugs. ‘‘ There is now an opportunity for even our most treatment-experienced (resistant) patients to get their viral load (down) to undetectable levels,’’ claims Eron, from the University of North Carolina. He predicts some of these drugs will be options for first-line therapy.
Southern California-based molecular biologist John Rossi goes further. Last week his group at the City of Hope Beckman Research Institute began the first of two trials of a treatment combining genetically engineered
Exciting times: John Kaldor says amazing leaps in treatments have come over the last two years