Researchers uncover new approach to suppress HIV production

A study by The Scripps Research Institute in Florida shows how a new compound can suppress production of HIV and prevent viral rebound.

The Scripps Research Institute scientists, from left, Susana Valente, Cari F. Kessing and Chuan Li, have come up with a new compound can suppress production of the HIV virus and prevent viral rebound. Photo courtesy The Scripps Research Institute
The Scripps Research Institute scientists, from left, Susana Valente, Cari F. Kessing and Chuan Li, have come up with a new compound can suppress production of the HIV virus and prevent viral rebound. Photo courtesy The Scripps Research Institute

The findings could completely change the approach researchers have used in the search for a cure for the human immunodeficiency virus.

“No other anti-retroviral used in the clinic today is able to completely suppress viral production in infected cells in vivo,” Susana Valente, TSRI associate professor, said in a press release. “When combining this drug with the standard cocktail of anti-retrovirals used to suppress infection in humanized mouse models of HIV-1 infection, our study found a drastic reduction in virus RNA present–it is really the proof-of-concept for a ‘functional cure.'”

The study, published today in Cell Reports, describes the Block-and-Lock approach, which blocks reactivation of HIV in cells. It locks HIV into a durable state of latency even during interruptions in treatment.

Researchers used a derivative of the compound didehydroCortistatin A, or dCA, to block replication in HIV-infected cells. dCA does this by inhibiting the viral transcriptional activator Tat, which halts viral production, reactivation and replenishment of the latent viral reservoir.

“Combining dCA with anti-retroviral therapy accelerates HIV-1 suppression and prevents viral rebound after treatment interruption, even during strong cellular activation,” Valente said. “It’s important to note that our study uses the maximum tolerable dose of the drug–with virtually no side effects.”

The team analyzed the combination therapy in a mouse model and found that once the treatment regimen was stopped, viral rebound was delayed up to 19 days compared to seven days with just anti-retroviral treatment.

“This demonstrates the potential of ‘block-and-lock’ strategies,” Cari F. Kessing, TSRI research associate, said. “This study shows that a ‘functional cure’ approach can succeed in reducing residual virus in the blood during anti-retroviral treatment and limiting viral rebound during treatment interruption.”

By Amy Wallace