Gilead's Preclinical Combo Trial Might Eradicate HIV

To date, treatments for HIV/AIDS have done a remarkable job of controlling the disease, but nothing has been able to totally eradicate the presence of the AIDS virus in patients’ bodies. Gilead Sciences announced promising results from a preclinical trial conducted with Beth Israel Deaconess Medical Center as part of an HIV eradication strategy.

Gilead Sciences, Inc. and Beth Israel researchers studied the combination of an oral toll-like receptor 7 (TLR7) agonist, GS-9620, and a broadly neutralizing antibody (bNAb), PGT121, in simian-human immunodeficiency virus (SHIV)-infected rhesus monkeys on suppressive antiretroviral therapy (ART). The combination treatment showed a subset of animal subjects that maintained viral suppression after ART was halted.

"HIV has the ability to hide in certain immune cells, which is called the latent viral reservoir and which represents a key barrier to curing HIV," said Dan Barouch,professor of Medicine, Harvard Medical School, and director, Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, in a statement. "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. In this proof-of-concept preclinical study, 45 percent of the animals that received both GS-9620 and PGT121 did not demonstrate viral rebound after stopping ART, suggesting that this combination may be able to target the viral reservoir in virally suppressed monkeys."

PMLive notes, "To date, Timothy Brown remains the only case of what could be described as HIV eradication in a person with the virus. In 2008, he received a combination of chemotherapy to destroy his immune cells and two bone marrow transplants, which seemed to have removed all traces of HIV in his body although some analytical tests have suggested he still has very low levels present."

In the trial, 44 SHIV-infected rhesus monkeys began ART on the seventh day after infection. After 96 weeks of continuous ART, they were split into four equal groups. Groups received either five doses of PGT121, 10 doses of GS-9620, both PGT121 and GS-9620, or placebo. The monkeys received ART throughout this period and for another 16 weeks. ART was halted at week 130 and viral rebound was monitored.

Once ART was halted, 11 of 11 animals in the placebo group showed viral rebound with a median rebound time of 21 days. Of the animals that only received PGT121, nine of 11 monkeys showed viral rebound. In the group that only received GS-9620, 10 of 11 animals showed viral rebound. In the group that received the combination of both compounds, five of 11 animals showed no viral rebound for at least 168 days. The other six monkeys in the combo group showed viral rebound, but then started to re-suppress the virus without ART.

"We remain committed to researching and developing HIV eradication strategies, and we are encouraged by these data presented at CROI [Conference on Retroviruses and Opportunistic Infection] from a preclinical animal model of HIV infection showing that the combination of GS-9620 and PGT121 may potentially induce viral remission in the absence of ART," said Norbert Bishofberger, Gilead’s executive vice president, Research and Development and chief scientific officer, in a statement. "GS-9620 is currently in a Phase Ib dose-escalation study in ART-suppressed people living with HIV and we have advanced GS-9722, a derivative of PGT121, into Phase I testing."

The research has the support of the Bill & Melinda Gates Foundation and the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health.

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