HIV/AIDS 2015: Changing treatment while pushing for a cure
January 1, 2015 | by Nicole White
HIV/AIDS researchers are determined not only to cure the disease, but to develop ever-more-effective treatments until that ultimate goal is reached. In 2015, they will gain ground in both endeavors.
In search of a cure: Stem cell and gene therapy
One of the most promising prospects for curing HIV is to recreate the success of the so-called Berlin patient, a patient with HIV who received a stem cell transplant to treat his acute myeloid leukemia. The transplant cured the man’s HIV because the donor had a previously unknown mutation that prevents the body from creating a key white blood cell receptor needed to establish an HIV infection.
The challenge for scientists has been to overcome the need to find a donor with the mutation who would also be a stem cell match for the patient with HIV/AIDS – a rare combination. Now City of Hope scientists have two promising approaches – both using stem cells. The approaches will be studied in City of Hope's new Alpha Clinic for Cell Therapy and Innovation, funded by an $8 million grant from the California Institute for Regenerative Medicine.
One approach is a combination of stem cell and gene therapy using small ribonucleic – or RNA – molecules that block the genes HIV needs to infect immune cells, specifically T cells. Developed by John Rossi, Ph.D., Lidow Family Research Chair and chair of the Department of Molecular and Cellular Biology, this approach aims to spur to spur the immune systems to produce T cells resistant to HIV by infusing the patient with these altered stem cells.
Another approach uses an enzyme called a zinc-finger nuclease, or ZFN, as a pair of molecular scissor that can edit the HIV patient’s stem cell genes so they no longer produce a key protein the virus requires to infect cells. This approach has been developed by a team of investigators at City of Hope working with Sangamo Biosciences and Keck School of Medicine at USC.
Such work won’t produce a cure overnight, but scientists are confident that their work will produce new breakthroughs in the year ahead.
Stem cell transplants for HIV-linked lymphomaThen there’s the matter of improving treatments in patients currently infected with HIV/AIDS. Traditionally, HIV has been considered a reason to exclude patients with lymphoma from transplantation, especially at centers that do not specialize in HIV.
Now, based on the results of a multicenter trial led by City of Hope, researchers say that patients with HIV-related lymphoma should be considered for autologous stem cell transplants.
The findings were shared at the annual meeting of the American Society of Hematology, and were called “practice-changing.” The trial, conducted in centers with and without HIV specialization, found the outcomes for these patients were comparable to non-infected lymphoma patients. In fact, outcomes for HIV-related lymphoma patients and lymphoma patients followed in a control group show no statistically different outcomes for rates of survival, disease progression, treatment failure and treatment-related mortality.
“Excluding patients from stem cell transplants simply on the basis of HIV infection alone is no longer justified,” said Joseph Alvarnas, M.D., lead study author and director of Medical Quality and Quality, Risk and Regulatory Management at City of Hope. “Patients with well-controlled HIV should be offered transplant as a standard of care.”
In 1985, the median survival for patients with HIV diagnosed with lymphoma was less than two months. Advances in combination anti-viral therapy have allowed for many advances in treating HIV, and now treatments for lymphoma should follow suit. This trial builds on work done at City of Hope in the early 1990s, when City of Hope scientists were among the first to show that stem cell transplants are safe and feasible for patients with HIV-related lymphoma.