A new therapy for HIV that does not require a lifelong regimen of daily drug cocktails may be on the horizon if early indications from studies on mice prove effective in people, scientists at the Scripps Research Institute in Florida announced Tuesday in the journal, Cell Reports.
Combining a new drug compound with existing antiretroviral medicines in HIV-infected mice, Scripps scientists reported that they had reduced the virus to undetectable levels and stopped it from rebounding for at least seven days after all treatment had stopped — raising the possibility of what the study’s authors called “a functional cure”.
Susana Valente, a Scripps Florida researcher and co-author of the study, said existing antiretroviral drug combinations dramatically reduce replication of the virus in people living with HIV, the virus that causes AIDS. But even with those potent drugs, she said, the virus still produces “a trickle” of particles that can add to the reservoir of HIV in the body and undermine the immune system over time, leading to chronic disease.
The drug compound tested by Scripps researchers, called didehydro-Cortistatin A, or dCA, completely suppressed the virus in mice when combined with existing antiretroviral therapies, according to the article.
Valente said dCA blocked reactivation of HIV in all cells — including those found in the brain, lymph nodes and liver — and then locked the virus into a “deep latency.”
“This shuts the virus down very, very strongly,” she said, “even stronger than what is happening during antiretroviral therapy.”
Dr. Paula Sparti, a retired family physician in Miami who has treated HIV and AIDS patients since the 1980s, said the research showed a lot of promise for future treatment.
“This has been what everybody has wanted to do forever,” Sparti said, “find something, a drug, that gets in and stops replication of the virus and does not allow healthy ... cells to get infected.”
Valente said she is encouraged by the findings, but acknowledged that much remains unknown.
“We still need to know over time what is the impact of really shutting down the virus,” she said. “What is the long term effect? Would we be able to reduce small events of viral production that might occur? Could we recover a lot of immune competence? And how long can we maintain people on this therapy? Could we replace the cocktail of drugs?”
The next steps for Scripps scientists in Palm Beach County, who conducted the study in collaboration with the University of North Carolina and the Walter Reed Army Institute of Research, will be to test the safety of the drug compound in monkeys and then in people before advancing to clinical trials.
Valente said she was encouraged by the early findings for dCA, particularly when the drug compound is used soon after HIV infection.
“The quicker you shut down the virus,” she said, “the smaller the reservoir.”
And if clinical trials find that dCA is effective on its own for treating HIV — or just reduces the frequency and number of drugs patients have to take — then the compound could also stem the side effects of long-term antiretroviral therapy, which are starting to become apparent as people live longer with the virus, Sparti said.
“I spoke with someone last week who had terrible lipodystrophy,” she said, referring to a disorder in the way the body uses and stores fat, which can change a person’s appearance. Sparti said there’s also growing evidence that long-term use of antiretroviral therapy can raise patients’ risk for cardiovascular diseases and lymphoma.
Valente cautioned it’s too early to know how dCA will work in people living with HIV. She called the study’s findings “a proof of concept of a different way to tackle” HIV, which has spiked in South Florida in recent years, according to the Centers for Disease Control and Prevention.
“It’s not saving the world,” she said. “The idea here is if we understand this very carefully, we might be able to move to a single drug or a drug that doesn’t have to be taken that often.”