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We have been in the era of the human immunodeficiency virus (HIV) for more than 40 years now. While antiviral treatments for the disease have been developed and are improving, there is still neither a cure nor a vaccine to prevent its transmission. And despite improvements in treatment, HIV is still killing people, an estimated 630,000 people worldwide. Fifteen years ago Leor Weinberger, a biophysicist at the University of California at San Francisco, thought of a different strategy to treat HIV and reduce infection rates: Engineer an HIV-like virus that is harmless, and infects HIV patients with it. The idea is that the harmless HIV could crowd out the harmful one by reproducing more quickly. Weinberger calls these fake HIVs “therapeutic interfering particles” or TIPs.
Weinberger became intrigued by the novel antiviral strategy in graduate school when he learned that cultured influenza virus would sometimes produce defective variants that blocked the “wild type” virus. He began doing experiments with defective HIVs in 2007, but it took until 2018 to develop one with the properties he wanted.
He stripped or crippled HIV’s genes to create the TIP’s RNA genome but left sequences that help it replicate. To do so, this neutered HIV genome “parasitizes” the molecules made by the HIV already infecting the cell, including its capsid proteins, which form a shell around the TIP’s RNA. Because the TIP’s genome is simpler than HIV’s, the variant can copy itself more rapidly. “Most of the interference occurs because the TIP genomic RNAs are grabbing capsid better because there’s more of them,” Weinberger says.
Now, for the first time, there is a result providing proof of concept for TIPs. Monkeys infected with the simian version of HIV, when treated with TIPs, showed a 10,000-fold reduction in the viral loads of the simian virus for “prolonged periods.”
While this strategy shows promise, there are also potential dangers that require careful study. While the TIPs might prevent reproduction and spread of HIV, they might cause other problems such as inflammation. Also, HIV patients might endanger themselves if, after Tip treatment, they opt to end ongoing antiviral treatment.
Others have pointed out that patients treated with TIPs might transmit the TIPs to sexual partners, which raises ethical questions. While some see such transmission as a positive, by spreading this potential HIV blocker to others, possible lack of disclosure among those involved is troubling.
