Treatment News : Animal Studies Suggest Anti-Reservoir Drugs May Help 'Functionally Cure' HIV

Drugs targeting HIV reservoirs in the body may result in spontaneous control of viral replication, in the absence of antiretroviral (ARV) therapy, according to a new study involving 18 monkeys conducted by Andrea Savarino, MD, PhD, of the Istituto Superiore di Sanità in Rome and his colleagues. The new findings, among the most noteworthy at an HIV eradication conference recently held in St. Maarten, in the Caribbean, could prove highly useful as researchers continue exploring ways to functionally cure HIV infection.

Though much attention is being paid to efforts to achieve sterilizing HIV cures—those akin to what was achieved in Timothy Brown, the “Berlin Patient,” who underwent high-dose chemotherapy and two stem cell transplants to render his immune system impervious to HIV and essentially snuff the virus out completely—there are also proposed strategies to achieve functional HIV cures. With a functional cure, HIV remains detectable in the human body, but no viral replication is found in the absence of ARV therapy.

Typically, discontinuing ARV therapy leads to a rapid rebound in viral load, likely because HIV persists in a large number of long-lived cellular reservoirs in the body that are not affected by standard medications. Some researchers believe that the immune system does have the ability to keep viral replication in check, but that the high volume of HIV that returns following ARV treatment discontinuation quickly overwhelms the immune system. In turn, some scientific teams have been interested in pairing drugs that attack cellular reservoirs of HIV with standard ARV therapy, to see if they can blunt the proliferation of virus following treatment discontinuation and therefore provide the immune system with an opportunity to maintain control of the virus on its own.

Researchers such as David Margolis, MD, at the University of North Carolina in Chapel Hill are studying HIV reservoir-targeting therapies in human subjects. Meanwhile, there is much to be gained from exploring similar approaches in animal models, notably macaques infected with SIV, HIV’s simian counterpart.

The experiments conducted by Savarino and his colleagues involved 18 SIV-infected macaques receiving ARV therapy and, in some cases, drugs targeting long-lived SIV reservoirs. Five macaques in particular received ARV therapy in combination with auranofin—an approved medication, sold under the brand name Ridaura, used to treat rheumatoid arthritis and previously shown to be capable of killing memory CD4 cells (a major long-lived HIV reservoir)—and the glutathione synthesis inhibitor buthionine sulfoximine (BSO), which has been shown to help eliminate HIV-infected cells.

After a series of treatment cycles combining ARV therapy first with auranofin and then with BSO, extremely low viral “set points”—viral loads below 200 copies in the absence of treatment—were maintained for more than 100 days in three of the macaques.

“The change in viral load set point was positively correlated with the number of drugs potentially acting against the viral reservoir that the monkeys had received,” Savarino and his colleagues wrote in the study abstract, “thus suggesting that drugs acting against viral targets alone”—such as antiretrovirals—“are insufficient to induce viral load containment in the absence of therapy.

“The results of the present study,” the authors conclude, “show that anti-reservoir strategies may indeed result in spontaneous control of viral load in the chronic phase of the infection and pave the way to a functional cure for AIDS.”

Ian, Jakarta, 2012-04-04 02:04:39
keep the hope fellas, i know it's still a long journey for us to find the cure.. but I'm sure we'll see it soon.. functional cure is better than no cure at all right? i believe when there's functional cure for this disease, the stigma wont be like today..

Arthur Gittleman, Bella Vista AR, 2012-02-15 07:42:46
Considering that the current HIV drug treatment is not all that good as the life of the patient is cut short and would not get too hopefully for fast solution to a cure. This is just a start to finding a cure. And please stop with the toxic drugs as the cure maybe worse than the disease.

Shortstack, Pittsburgh, 2012-01-09 01:00:40
What happens when they find a functional cure? Will we all just have to live with this virus, and the stigma that goes with it? Because it's not a complete cure, we could still pass it on to our partners, and possibly an unborn child.

babyspirit, atlantic city, 2011-12-26 21:41:59
this is great news. i have been poz since '96, and i always have hope. a functional cure is a step in the right direction, and i'd be willing to try it. i am thankful to all those involved in the scientific research.

Julio, Guatemala, 2011-12-21 12:42:01
It would be great to find a cure. Nevertheless, we have to keep on fighting till the end with an optimistic thinking way. My life's been more fruitful than ever since I'm HIV positive. Do not get desperate, live fully and joyfully. Sorry, my English is not good.

Jose, Miami, 2011-12-18 19:33:10
Atleast these drugs are already approved by the FDA. I would think this would be much faster than traditional drug development.

alberto, manchester, 2011-12-17 01:27:27
The drug to watch is bit225 by biotron in australia. Its a vpu inhibitor which has been shown to be the protein which keeps virus dormant in the reservoirs. With vpu inhibited the reservoirs will awake and can be destroyed by antivirals. Bit225 is in phase 2 trials for hiv which will be complete by spring 2012, it also treats hepatitis c and looks very promising. The cocktail i think we are looking at is bit225,zolinza,prostratin,raltegravir,truvada for 12 weeks equals cure. Its going to happen

Steve, Las Vegas, 2011-12-16 09:53:24
What makes me more sick than HIV, is the idea of anyone or any group or organization centered on HIV that does not seek, embrace, demand, and help bring about a cure. The fact that on the contrary, many poz people here are literally throwing stones at the tireless research of scientists dedicating their lives to cure this virus and save millions - is more sickening to me than any affliction HIV has caused. There are times when a slap in the face is in order - the HIV community deserves a big one

Steve, Las Vegas, 2011-12-16 09:42:57
1st of all, thank you for posting this article Poz.com.

This is huge news, yet as the comments here show, the biggest hurdle the cure has is literally the lack of enthusiasm or attention those who'd benefit most from it. Take the other comments on this article as an example. One person listed 6 'promising leads' that he claimed were "never heard of again". Wrong. Sangamo has had nothing but news and good news at that in the last few months about their gene therapy cure. Do your research.

Phyllis Dorman, West Springfield, 2011-12-15 18:14:11
i just wish for the reasearchers tp look for a cure asap so i can liove little bit longer it s been years and years ands no cure s there!! im so frustrated!!!!

kolo, Warsaw, 2011-12-15 10:23:29
how long does it takes? 5?,10?,20 years?, no one know

Ranjan, , 2011-12-15 05:20:14
In the last 3 years we have heard of atleast 6 promising leads only to be never heard of again. 1. Israeli scientists with some peptide which was patented 2. Sarawak scientists common study with american scientists in advanced stage of Bintagor plant source 3. Wonder pill to cure all viruses 4. Sangamo, Gilead and some viral action delay and many more. ts about time announcements be made only when breakthrough is achieved instead of raising false hopes. Any idea how the affected feel

WC, , 2011-12-14 11:50:18
While this is great news, if the virus is not killed or eradicated entirely it's not a cure. Seems this would simply be a better and advanced treatment option, but in no means a cure; maybe a step closer to a cure, but again, not a cure...