Gold-based Drug May Pave the Way to a Cure for AIDS
A new breakthrough in AIDS research is reported by an International group in the journal AIDS, the leading scientific publication in the field.
Rome, April 20, 2011 - For Immediate Release-
Using a compound containing gold and approved for treatment of rheumatoid arthritis, researchers (from the Italian Institute of Health, “La Sapienza” University of Rome, the Vaccine and Gene Therapy Institute, Florida, and Bioqual, Maryland) have been able to hit the hidden stock of HIV which cannot be targeted by current antiretroviral therapies. Similarly to the dark matter in a galaxy, in this stock the virus is of course physically present but in a form that can hardly be measured precisely and cannot be targeted by drugs or the immune system. The larger this “dark stock”, the more difficult it is for the immune system to keep the infection under control. In the new study, conduced in monkeys infected with a virus very close to HIV, the so-far elusive hidden viral stock (which scientists refer to as the reservoir) has for the first time been struck by a drug-based attack in the chronic phase of the infection. HIV lies “stocked” in a dormant form in one particular type of immune cells, i.e. the central and transitional memory CD4+ T-cells. These cells are long-lived, and cannot be eliminated by the immune system because the virus is hidden. If antiretroviral therapies are suspended, sooner or later, the virus will wake up thus re-starting the progression of the disease. In order to rid HIV from the body, the cells harbouring the dormant virus must be eliminated. This goal has been the “Holy Grail” of AIDS research, at least in the last few years.
We serendipitously found that one drug that we were evaluating as a candidate for the shock and kill caused the death of the central memory T-cells, leaving their precursors (i.e. the naïve cells) partially intact
The majority of the scientists in the field are trying different types of strategies aimed at the same goal. These are the so-called shock-and-kill strategies, which attempt to “smoke out” the dormant virus and attack it thereafter. “We have also tried the shock-and-kill approach” said Dr. Andrea Savarino, lead author of the study, “but we serendipitously found that one drug that we were evaluating as a candidate for the shock and kill caused the death of the central memory T-cells, leaving their precursors (i.e. the naïve cells) partially intact”. “This happened”, he adds “without awakening the virus, which is a risky procedure. We knew that eliminating the central memory T-cells might also be risky, but it was an attractive new approach that was tempting to try because these cells can be replaced by the organism starting from a naïve source. Our monkeys showed, upon suspension of all therapies, an improved capacity to keep the infection under control; one of them maintained a low viral load and high CD4 counts [i.e. the cells that HIV depletes] for one year”. This type of phenomena can be defined as a sort of remission of the infection, though not yet a cure, because the viral nucleic acids are still detectable, although they are maintained at low levels.
“However, as the side effects of this approach in the presence of HIV are as yet largely unexplored”, Dr. Savarino concludes, “I strongly recommend that people living with HIV/AIDS do not buy the drug from uncontrolled sources such as the e-Bay and start self-treatment outside highly medicalized settings.”
The authors of the study have decided to wait a little before moving to clinical trials. “We prefer not to involve people in a trial of the drug immediately”, says Dr. Enrico Garaci, president of the Italian Institute of Health, and co-author of the study, “that’s because in this phase the trial could only be a proof-of-concept study, and we have already this proof in monkeys. We prefer to put all our effort in the intensification of the attack on the virus reservoir in monkeys by using a combined approach”. “This will also allow”, he adds, “a more thorough evaluation of the safety of the approach”. Now the big challenge will be to restrict the viral reservoir below a certain threshold and see whether this will allow the immune system to keep the infection under permanent control.
Animals were hosed at Bioqual, MD, USA, in accordance with strict ethical standards.
Lewis, M.G.; DaFonseca, S.; Chomont, N.; Palamara, A.T.; Tardugno, M.; Mai, A.; Collins, M.; Wagner, W.L.; Yalley-Ogunro, J.; Greenhouse, J.; Chirullo, B.; Norelli, S.; Garaci, E.; Savarino, A. Gold drug auranofin restricts the viral reservoir in the monkey AIDS model and induces containment of viral load following ART suspension. AIDS., POST ACCEPTANCE, 18 April 2011 doi: 10.1097/QAD.0b013e328347bd77
Andrea Savarino, M.D.
Dept. of Infectious, Parasitic and Immune-mediated Diseases
Istituto Superiore di Sanità
Viale Regina Elena, 299
00161 Rome, Italy.
Phone: +39 06 4990 2305
FAX: +39 06 4990 3561
Key words: HIV reservoirs, hiv cure