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HIV: functional cure is the most likely option—with patients in permanent remission after stopping treatment
Top AIDS scientists were optimistic Wednesday of finding a cure for the disease that has claimed 30 million lives—but said it might not work for all people.
The experts have high hopes for a treatment that will be given at an early stage of infection—most likely a cocktail that includes an immunity booster and a virus killer.
But they said people with a long-running, untreated infection and a compromisedimmune system may never benefit from an envisioned "functional cure"—which means a person retains traces of the virus but no symptoms.
"We have had some very interesting little lights at the end of the tunnel in individual studies," Anthony Fauci, director of the US National Institute of Allergy and Infectious Diseases, said on the sidelines of a Paris conference to mark the 30th anniversary of the discovery of HIV, the virus that causes AIDS.
"It is a difficult road, but a feasible road," he said.
Proof of vaccine feasibility lay with a Thai study dubbed RV144, which in 2009 demonstrated protection for 31 percent of some 16,000 people given an experimental vaccine, said Fauci.
"I think we will likely have a (vaccine that works at) better than 31 percent, but there's certainly the possibility that we won't have a 90 percent," Fauci told reporters.
"And I think there is even a greater possibility that we won't have a pristine cure that would essentially cure everybody who is HIV infected.
"I think it's not only possible that that won't happen—I think it is likely that that won't happen."
Fauci and other scientists point to the difficulties they have encountered to completely expunge the virus that destroys the immune system and exposes infected people topneumonia, TB, and other opportunistic disease.
Antiretroviral drugs slow down virus reproduction, allowing people to live symptom-free lives and slowing transmission to others, but much of the virus hides away in "reservoir" cells only to reemerge and start spreading again once treatment stops.
A team of scientists at Monash University in Melbourne, Australia, is experimenting with an anti-cancer drug to flush the virus out of its hiding place, then to be killed.
"Ultimately, we want a cure that is available to a large number of people," a member of the team, Sharon Lewin from Monash University, told AFP at the conference.
"I think the virus is persistent in people for multiple reasons, not one reason... now we are looking at the virus that hides in the DNA, we are finding the way to take on part of the problem. Ultimately we will need a combined approach, like we had for cancer."
Two other, smaller studies using antiretrovirals at a very early stage of infection, before viral levels build up, have excited hopes of a cure.
One involved a baby in the US state of Mississippi apparently cleared of the virus after being given aggressive antiretroviral treatment within 30 hours of birth.
The other is a small French study of 14 HIV patients, known as the VISCONTI cohort, who started on drugs within 10 weeks of infection and were able to stop the daily treatment after three years, staying healthy.
For Francoise Barre-Sinoussi, a 2008 Nobel co-recipient for the HIV discovery, a functional cure is the most likely option—with patients in permanent remission after stopping treatment.
"The international scientific community agrees that it will likely not be a single drug, but a combination of molecules and drugs with a vaccine that will allow this remission," she said.
An estimated 34 million people are infected with HIV worldwide, and about 1.8 million die every year.
Fauci would not be drawn on the timing for a vaccine for people most at risk, saying only: "It's not going to be 30 years, but it's not going to be a year."
Scientists discover how HIV kills immune cells
Untreated HIV infection destroys a person's immune system by killing infection-fighting cells, but precisely when and how HIV wreaks this destruction has been a mystery until now. New research by scientists at the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, reveals how HIV triggers a signal telling an infected immune cell to die. This finding has implications for preserving the immune systems of HIV-infected individuals.HIV replicates inside infection-fighting human immune cells called CD4+ T cells through complex processes that include inserting its genes into cellular DNA.
The scientists discovered that during this integration step, a cellular enzyme called DNA-dependent protein kinase (DNA-PK) becomes activated. DNA-PK normally coordinates the repair of simultaneous breaks in both strands of molecules that comprise DNA. As HIV integrates its genes into cellular DNA, single-stranded breaks occur where viral and cellular DNA meet. Nevertheless, the scientists discovered, the DNA breaks during HIV integration surprisingly activate DNA-PK, which then performs an unusually destructive role: eliciting a signal that causes the CD4+ T cell to die. The cells that succumb to this death signal are the very ones mobilized to fight the infection.
According to the scientists, these new findings suggest that treating HIV-infected individuals with drugs that block early steps of viral replication—up to and including activation of DNA-PK and integration—not only can prevent viral replication, but also may improve CD4+ T cell survival and immune function. The findings also may shed light on how reservoirs of resting HIV-infected cells develop and may aid efforts to eliminate these sites of persistent infection
Sunday, June 9, 2013
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