NIAID director notes long remissions may be more achievable
DURBAN, South Africa, 16 July 2016 — History suggests that finding a “classic” cure for HIV — clearing the virus from the body — is going to be a tough chore, a top U.S. official said here.
On the other hand, a less aspirational goal — that of achieving sustained remissions from the virus — looks closer to hand in the current state of medical science, according toAnthony Fauci, MD, director of the NIH’s National Institute of Allergy and Infectious Diseases.
The human immune system can cope with other viruses but HIV is almost never cleared so to cure the infection, “we have to do things that nature has never before done,” Fauci told reporters gathering for the International AIDS Conference.
A classic cure is “certainly not impossible, but very challenging because of the very special nature of HIV,” Fauci said before giving a keynote address at apre-conference symposium dedicated to the science of curing HIV.
That “special nature” is a well-known conundrum — the virus inserts itself into the genome of immune cells, the very mechanism that the body uses to get rid of pathogens. Many of those cells die in the production of new viral particles, leading to immune deficiency if the process is not interrupted by medication, but others become quiescent.
That reservoir of infected cells can restart active HIV growth if treatment is stopped, usually within days or weeks, and there is currently no way known to get rid of them.
Fauci noted that four main approaches to a classic cure, some more promising than others, have been tried, but so far without success:
- Depleting the reservoir with various drugs has a history dating back 2 decades; patients universally see their infection rebound when anti-HIV drugs are stopped.
- Attacking the reservoir cells with immunotoxic therapies, an approach borrowed from oncology that is showing “some promise” in early HIV studies.
- Transplanting immune stem cells that lack a protein needed for HIV to infect them; the so-called Berlin patient, Timothy Brown, was the first — and so far only — case where the approach has succeeded.
- “Editing” immune cells to make them immune to HIV, an idea inspired by the Brown case; it’s too early to tell if the process can be made to work or if it can be widely applied.
Attaining a sustained viral remission, which would allow anti-HIV medications to be stopped for long periods of time without fear of viral rebound, is “likely more feasible,” Fauci said.
For such an approach to work, “you need to start with a small reservoir and a competent immune system,” he said.
In other words, patients need to be treated as soon as possible after infection, something that is now recognized in treatment guidelines, to reduce the growth of the reservoir and the damage to the immune system.
In rare cases, he noted, that early treatment might be enough that a patient’s immune system can later control the virus by itself.
Fauci said another approach, is to develop a therapeutic vaccine — a drug that would boost the immune system and allow it to fight the virus. None has succeeded so far, but clinical trials of candidates are under way, he said.
But the discovery of more than 200 broadly neutralizing antibodies against HIV suggests they might form the basis of a third approach, he added.
In the course of most other infections, such antibodies are produced within days or week, but in HIV it takes years and by that time they are of little use to a patient.
Fauci said several labs, including his own, are conducting studies to see if passive transfer of broadly neutralizing antibodies can induce a long lasting remission.
The answer? Not yet.
But in a small cohort of patients with virus fully controlled by medication, infusions of an antibody dubbed VRC01 extended the time patients could remain off their anti-HIV drugs at a median of 39 days. Historical data suggested that viral rebound usually begins between 11 and 28 days.
The result is “not a home run of any sort,” Fauci said, but it suggests there was an effect. And when he and colleagues delved deeper into their data they found that patients who had pre-existing resistance to VRC01 tended to rebound in line with the historical controls, while those whose virus was sensitive to the antibody had a longer time to rebound.
One implication is that the antibody needs to be more potent and long lasting, he said, and another might be — in parallel with the development of today’s triple-drug HIV therapy — that more antibodies need to be used.
The prospect of an HIV cure, long dismissed as impossible, has been resonating for several years. It’s especially important for HIV-positive children who face a life that has never been free of powerful medications, commented Jintanat Ananworanich, MD, PhD, of the U.S. Military HIV Research Program.
“Having a remission, having a cure would have an enormous impact,” she stated.
Children are ideal candidates for a cure using Fauci’s criteria, Ananworanich said, as they almost always can be treated very early in the disease course. And because their immune system is developing, the virus might find it more difficult to hide in a reservoir.
While many people are still not on treatment around the world, current therapies are highly effective, easy to take, generally well tolerated, and offer an almost normal lifespan.
“As physician-scientists, “we have to make sure that what we do for a cure is better for the patient than what they are now receiving,” Fauci cautioned.
By Michael Smith