Searching for HIV cure, Gilead’s new ‘shock and kill’ combo swats back lethal virus in monkeys

A prominent group of scientific investigators has taken another step toward a possible eventual cure for HIV — one of the longest and most difficult trails in drug R&D — using a combo drug from Gilead.

While combination therapies have long proven able to keep HIV locked into hidden cellular reservoirs, eliminating those viral pockets has proven to be devilishly difficult. In a new animal study involving rhesus monkeys, though, researchers at Harvard working at Beth Israel Deaconess Medical Center advanced a lengthy effort in pursuing a “shock and kill” strategy using a toll-like receptor combined with a killer antibody.

Gilead’s experimental TLR7 agonist GS-9620 did the shocking, and the antibody PGT121 did the killing. And while they weren’t able to eradicate the reservoirs, the researchers were able to do a good enough job to allow close to half the monkeys in the combo arm of the study to go without antiretroviral for a lengthy stretch, raising the promise that the same might be accomplished in a large subset of human patients.

Dan Barouch

To test this approach, investigators took 44 monkeys infected with a simian form of the virus and divided them into 4 groups. They left one group in the placebo arm, dividing the rest into two groups which were treated with one of the two treatments alone and one group taking a combination. Then they took them off therapy.

While the virus in most of the monkeys in the placebo or two monotherapy arms quickly rebounded, ready to kill as ever, 5 of the 11 primates in the combo arm were able to go at least 168 days without rebounding, with the other 6 rebounding but then able to suppress the virus without antiretroviral therapy (ART).

Gilead has now advanced the two treatments in Phase I studies as they start to test how humans will respond. Nonhuman primates have long been considered an ideal model for antiviral therapies.

Why is this important?

While patients respond to longterm cocktail therapies, they also experience greater vulnerability to a variety of maladies that can shorten their lives. The prospect of going off ART for lengthy periods would hold the promise of significantly reducing those risks.

“New HIV therapies that aim to wake up and target the viral reservoir have the potential to play an important role in long-term viral suppression without ART,” said Harvard professor Dan Barouch, the director at the Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center.

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