Research Press Release

Drug discovery: A new candidate for HIV treatment

Nature

July 2, 2020

A new, long-acting antiretroviral agent that shows potential for the treatment of HIV infection is described in Nature this week. Preliminary clinical studies demonstrate a reduction in the viral load in patients with HIV after a single dose of the agent, which can remain active in the body for more than six months after administration.

Daily oral doses of antiretroviral drugs are used to manage HIV infection, but some individuals experience drug resistance that reduces the treatment effectiveness. New longer-acting drugs could increase options for those with resistant strains of HIV, as well as improve adherence to treatment regimens.

Stephen Yant and colleagues describe the development of a small molecule called GS-6207 that disrupts the HIV capsid, the protein shell that encloses the viral genome. Building on previous work, the authors designed GS-6207 to bind tightly to capsid proteins, interfering with multiple interactions essential for viral replication. GS-6207 is shown to be active against multiple strains of HIV in laboratory experiments and acts synergistically with approved antiretroviral drugs, making it an ideal addition to combination treatments. A clinical study in 40 healthy individuals indicates that GS-6207, which is delivered via injection, is generally safe and well-tolerated and can remain active in the body for more than six months after administration. A subsequent phase-1 trial in 32 patients with untreated HIV-1 infection resulted in reduction (but not total clearance) of the viral load 9 days after treatment.

Most small-molecule antiretroviral drugs for HIV treatment work by interfering with viral enzymes, but the latest findings support targeting the capsid protein as a promising way to treat HIV infection. The authors also suggest that the infrequent dosing requirements of this small molecule may also make it a candidate for preventing HIV infection in at-risk populations, although this was not tested in the present study.

doi:10.1038/s41586-020-2443-1

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