September 9, 2008

A 'Functional Cure' for HIV?

Anthony Fauci, MD, the head of U.S. governmental AIDS research, isn’t ready to give up on finding a cure for HIV. Dr. Fauci talks with AIDSmeds.com about placing what he called a “functional” cure front and center at last month’s XVII International AIDS Conference.

Using the current crop of antiretroviral (ARV) drugs to cure HIV in the traditional sense—eradicating the virus from the body—may not be possible. But according to a provocative lecture delivered last month at the XVII International AIDS Conference (IAC) in Mexico City, Anthony Fauci, MD, a noted AIDS researcher and long-time head of the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH), suggested that it may be possible to achieve a “functional” cure—a lifetime without symptoms, disease progression or prolonged ARV treatment—if a short course of HIV therapy is started immediately and aggressively by people newly infected with the virus. And if this proves possible, there’s hope of doing away with the need for expensive and potentially toxic treatment in others who have been living with HIV for months or years.

Dr. Fauci doesn’t use the word “cure” lightly. Several years ago, his own laboratory started HIV treatment in a small group of people newly infected with the virus. Fauci’s team thought they had achieved the impossible when they were unable to detect the virus in some patients who responded well to therapy. When treatment was stopped, however, the virus came surging back. “I’ve been in this boat before, where I couldn’t find virus, and then when I stopped therapy the virus came back, so I’m very, very cautious about that,” Fauci says.

Subsequent research explained why this approach didn’t work. In the days and weeks after a person becomes infected, the virus quickly finds its way into cells throughout the body and establishes what Fauci and others call a “reservoir” of virus. This reservoir includes cells that can live a long time and that ARV drugs can’t reach; it is what allows the virus to stage such a powerful comeback, even after years of keeping viral loads undetectable. Many scientists have conceded that getting rid of every viral particle in every cell—what Fauci calls a “sterilizing” cure—may be impossible.

However, at IAC and more recently in an interview with AIDSmeds.com, Fauci argued that we might now have the arsenal necessary to functionally cure HIV, at least in the newly infected. Compared with ARVs used in initial cure studies conducted more than 10 years ago, we now know which medications are the most potent and have several drug classes to draw from. Thus, if therapy is started early enough using a mega-regimen involving four or five classes of drugs, it may be possible to effectively prevent the HIV reservoir from becoming too large. If this can be accomplished, Fauci hopes, the immune system may be able to combat HIV on its own, ultimately allowing treatment to be stopped indefinitely without increases in viral load or decreases in CD4 cells.

Fauci acknowledges that such a functional cure probably wouldn’t work in everyone. However, if it does pan out in newly infected individuals, the research may illustrate ways to achieve similar results in those who have been infected for several months or years—possibly through using a type of immune-based therapy, such as a therapeutic vaccine. Moreover, he feels that keeping scientific and public attention focused on the hope of some kind of cure is vital to controlling the epidemic.

Sooner Rather Than Later

Fauci says that studies are already under way that will help build the scientific foundation for producing a functional cure. “One [of the studies],” says Fauci, “takes people who are very well controlled on [ARV] therapy, with undetectable viral loads, and then [intensifies treatment] with an integrase inhibitor as well as an entry inhibitor.” The goal of this study, he explains, is to see whether treatment intensification can decrease the size of the viral reservoir and halt the destruction of immune system cells needed to effectively control HIV in the body.

If treatment intensification achieves this, the next step would be to try it in people who started ARV therapy very early. “If you treat people early enough,” Fauci says, “so that the reservoir doesn’t get to a point that it’s so large that you’ll never get rid of it, but also preserve an HIV-specific immune response, you can essentially stop therapy and [still] keep the virus in check.”

Fauci likens a functional cure to the situation seen in “elite controllers”—HIV-positive people whose immune systems are naturally able to keep virus at undetectable levels without ARV treatment. Scientists are actively seeking the genetic makeup that sets the immune systems of elite controllers apart from the majority of people with HIV. Fauci concedes the possibility that a person may need to carry at least some of the same genetic mutations as elite controllers for a functional cure to work, but hopes that won’t be necessary.

While this is good news for people who start taking ARV treatment within days or weeks of infection—admittedly a tiny minority of people with HIV—what about everybody else? Fauci replies, “Are those people beyond my hopes of doing anything for? My answer is, No they’re not. It’s going to be more problematic, but in those people I hope that we could, with the right approach, diminish the reservoir the best we can [while also boosting immune responses] with the use of immunotherapy.”

While the addition of integrase and entry inhibitors to the ARV arsenal may have given us the tools to reduce the HIV reservoir, no immune-based therapy has yet made it to market. This means it could be a number of years before we’re able to boost the immune systems of people with HIV. Nevertheless, Fauci says, “I’m not giving up on those people by any means, but what I’d like to do first is establish a proof of concept where you stack all the cards in your favor first. And that’s what I was talking about in Mexico.”

An Untenable Situation

Because of the sheer size of the global HIV epidemic and the tremendous number of new infections each year, Fauci feels that it is vital for us all to stay focused on a cure, no matter how difficult the scientific challenge may be. Maintaining every single HIV-positive person in the world on ARV therapy, he says, “is an untenable situation.” The remaining options, he explains further, are two potentially workable solutions: “either prevent all infections, or produce a functional cure so that you don’t necessarily have to keep people on therapy for the rest of their lives.”

“We need to pursue both of those tasks,” Fauci continues. “We need to really do a full court press on prevention, but we also can’t give up on the possibility that in some people, we may be able to actually discontinue therapy [and achieve a functional cure].”

Search: Fauci, cure, eradication, functional cure, antiretrovirals, Fauci, NIAID, ARVs, treatment, acute infection, early infection, long-term nonprogressors, elite controllers, LTNPs, integrase inhibitors, entry inhibitors

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Previous Comments:

Karl Lynch, Phoenix, 2009-04-19 16:48:31
My cd4 count is 720. I,too would like to donate the rest of my natural life to find a cure. Please contact me when you receive this.

Aaron, Houston, 2009-03-09 19:15:33
I just found out i have hiv my cd4 count is 390 and my vl 2000 Im not on any meds... I would like to donate the rest of my natural life so that you may find a cure..... please when you receive this thank you...

keith boyd, new haven, 2008-12-18 04:06:59
My good days out weigh the bad I except this disease and Im realizing Im not crippled unless I mentally give up but today I live a normal life I had hiv since 88 I had hap c treatment and just had cataract surgery THEY WERE SUCCESSFUL THANK GOD.We have to stay humble and work and eat healthy and rest

Eric Lockwood, Spartanburg, SC, 2008-11-30 16:50:54
I started on AZT monotherapy in 89. Then Videx and AZT dual therapy (ALL WRONG). In the backwards state of SC I had to run for my life to Houston where my phenosense GT showed I had the R15 mutation and the M150 mutation. I decided to get on Reyataz with 100mg of Norvir with Viread and AZT and my VL has been less than 50 since 2/4/05 and now my T4 cells are 847 and my % is a respectable 24.2. I was also on methadone and cut my AZT to only 300mg QD. I'm 54.

Mike Warner, Scottsdale, 2008-11-02 18:31:13
Deforming peoples bodies and effecting there quality of life with drugs is not a cure. Go look at the monsters the drugs deform the bodies into then tell us its any form of a cure.

Marcus, Ottawa, 2008-10-14 11:43:45
The phrase "functional cure" needs to be used carefully a number of legal and ethical questions exist. HIV exposure is being criminalized in many countires and musing about functional cures could be interpreted by a + person as no longer needing to disclose their status to a - partner. Criminalization is premised on the 'level of risk' to the non-infected person but as we all know, 'non-detectable' is NOT non-risk. If you have HIV, you risk exposing someone if you are not safe.

JIRAH, , 2008-09-19 15:34:35
My husband for 18yrs is HIV + his girlfriend died last year.I am negative and we are still intamite without any protection.I went for a test and I am still neagtive.My husband has no been to a doc since he found out.He is not taking any medication.PLEASE TELL ME HOW IS THIS POSSIBLE

Waiting Game, phoenix, 2008-09-17 19:48:12
a functional cure sound like i'm a good canidate,it will keep my hiv from multipling, i do deserve that. hiv -pos july 2008. VA is not doing that route. should i seek another care option? before i even start treatment at VA.it doesn't help sitting waiting for my labs to drop to CDC standard levels or until i hit rock bottom to start medications u would think? labs vrl-5500 cd4-555 23%

gil, el paso tx, 2008-09-17 10:03:39
"Functional Cure"!? How about a Functional Life? Even if there was a pill that would rid the body of the HIV virus tomarrow, A vast majority of us would still be considered fully disabled. Im talking about the "long term" side effects of these medications. Heart disease, kidney and liver damage,Bone death, to name a few. The powers that be need to rethink their over zealous defense of these toxic drugs and drug company profits.

Edward, Phoenix, AZ, 2008-09-15 23:19:58
What has happened to the resurgance of interest in UBIT (Ultraviolet Blood Irradiation Therapy) used prior to Polio Vaccine. Same things were stated about Polio prior to the development of the vaccine. Yet UBIT was repeatedly successful in eliminating the virus without damage to the RBC's. UBIT was pushed aside once the vaccine was successful. Seems we should be looking into our past to find answers for our futures.

Todd Phillips, , 2008-09-13 14:31:33
Sounds like more BS promises from the same people who have managed to do little more than kill people slightly less quickly after a quarter of a century and billions of dollars of funds. Have some skepticism, people, and demand the same standards be applied to the experimental HIV drugs as are other drugs. And please, Fauci is the very last person that's going to help a cure come into being.

Fred Schmidt, Bronx,New York, 2008-09-12 12:07:50
I applaud Dr.Fauci for the idea of a Functional Cure at least it's a start Hiv hits hard and to hit it hard at the start makes a lot of sense Kimotheraphy hits hard also but its Effective. mabey its time to start getting tougher with HIV/AIDS.

Mark, Aztec, 2008-09-12 10:08:33
It sounds like Faiuci is basically calling for a ramped up PEP. If that is the case, it must be administered no later than 72 hours after initial infection. That just isn't going to happen. Half of the people now infected don't know they are carrying the virus. Even if they did find out, many of the treatment naive are so paranoid of the HIV meds they would probably refuse any such treatment. Sounds like more smoke and mirrors.

Aurora, virginia, 2008-09-11 21:36:53
i think a major thing this article overlooks, is the fact that most newly diagnosed dont find out immediatly after they contract it. it sounds as if by what is said that you would have to start fast and hard within days or weeks of contracting the virus. now lets be serious, i know i had to have had it for at least a year before i found out. so it doesnt really sound like this plan would be that functional for any one.

joseph k, Palo Alto, CA, 2008-09-11 21:27:10
Tell all the men who won't date me due to my status that I am "functionally cured." Tell the guy I infected last year that I am "functionally cured." This man is in the pocket of insurance companies and he delivered them a windfall with this irresponsible, inaccurate statement. The insurance companies are toasting each other over this one. I cannot imagine a more damaging thing could happen to the rights of PWAs. All for publicity. Time to dig in and ACT UP!