The Search for the Cure Heats Up! Part Three
Cure Strategies; Cure Realities
By Bob Frascino, M.D.
March 1, 2011
We've identified two main problems with this approach. First, the treatment "alarm clocks" designed to wake up the sleeping virus in CD4 cells would need to activate every single infected dormant CD4 cell in the entire body. If you missed any and then stopped ART, HIV could come roaring back once again. Second, the treatments tried so far act exclusively on the resting CD4 cell population. Unfortunately we are now realizing that these dormant long-lived cells are not the only reservoir for latent HIV.
A growing number of experts believe that a "functional cure," whereby HIV is disabled and/or the immune system is strengthened sufficiently to hold off disease progression when ART is discontinued, is an achievable goal in the very foreseeable future. This ART-free remission ("functional cure") may be a more realistic goal than the complete eradication of HIV. One mechanism for strengthening the immune system is therapeutic vaccination. Such a vaccine would not eradicate HIV, but might stimulate immune defenses to be more effective against HIV. This type of therapy would have the potential to transform HIVers into "long-term nonprogressors." There are a number of promising therapeutic vaccine candidates, but vaccine research is both time and labor intensive, and this experimental approach probably won't be ready for prime time any time soon.
There are other very novel strategies also being cautiously evaluated. One research company has developed a technology, which is now in very early clinical trials, that to some extent mimics what happened in the now famous "Berlin Patient". This strategy utilizes zinc fingers, which are in essence tiny molecular scissors that are designed to snip the CCR5 gene (not the receptor itself, but the gene that codes for the receptor) off the DNA within CD4 cells that have been removed from the HIVer's body and expanded (artificially multiplied). These genetically altered CD4 cells, which are now resistant to CCR5 HIV viruses, are then infused back into the patient. Whether the manipulated cells will survive and function normally is not yet known.
Just prior to the International AIDS Conference in Vienna in July 2010, the International AIDS Society (IAS) held a workshop titled "Towards a Cure: HIV Reservoirs and Strategies to Control Them." During the workshop information was presented about drugs called HDAC inhibitors, which have been shown to activate latent HIV in the test tube. Representatives from Merck discussed a trial of an HDAC inhibitor and another drug called a protein kinase C activator in monkeys. The approach was successful in decreasing viral load, but did not prevent viral rebound when ART was interrupted.
HIV expert Brigitte Autran presented the design of two promising clinical trials (Eramune 01 and 02) that will evaluate the effect of adding certain immune-based therapies to ongoing ART. Eramune 01 involves intensifying ART and stimulating the immune system with interleukin-7 (IL-7), a bioactive agent that may be able to deplete latent HIV from memory CD4 T-cells. Eramune 02 will test a therapeutic vaccine plus intensified ART. The goal is to strengthen the immune response to specifically recognize and destroy HIV-infected cells. Details of both clinical trials are available in the clinical trials database section at www.clinicaltrials.gov.
Other indications that the search for a cure has been elevated to a top-of-the-agenda item include:
- The National Institutes of Health has announced an eight-million-dollar grant program called the "Martin Delaney Collaboratory: Toward an HIV Cure." This program offers grants to research institutions that partner with industry to solve the key problems standing in the way of a cure for HIV.
- The non-profit organization amfAR has instituted a targeted program also supporting collaborative cure-related research called the amfAR Research Consortium for HIV Eradication (ARCHE).
- TAG (Treatment Action Group) is planning a workshop with amfAR focusing on clinical and regulatory issues related to HIV-cure strategies and clinical trials in an effort to accelerate and streamline the cure-research effort.
There is no doubt that in the search for a cure we often take two steps forward and then one step back. However, we are now certain that we are stepping on the correct path and the pace of our steps is dramatically quickening. The take-home message: A CURE IS NOT ONLY POSSIBLE; IT'S FINALLY IN SIGHT AND HOPEFULLY SOON WITHIN REACH!
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