An inhibitor of HIV infection that provides rhesus macaques with long-term protection from infection with simian HIV (SHIV) after one dose is described in Nature this week. This class of antiviral agents may have the potential to improve prophylactic approaches to reducing HIV transmission, although clinical trials will be needed to assess the effectiveness of these inhibitors in humans.
Pre-exposure prophylaxis (known as PrEP) with antiretroviral agents is an important strategy for HIV prevention, but this approach requires frequent administration of drugs, which can limit adherence and effectiveness. Long-acting antiretroviral agents could address the challenges of daily drug dosing. Dan Barouch and colleagues investigate the long-term prophylactic efficiency of GS-CA1, an agent that has demonstrated antiviral activity in mice. GS-CA1 is a small molecule that can inhibit the HIV capsid, an attractive target for antiviral agents as it has an essential role in virus replication.
A single dose of GS-CA1 protected macaques from repeated challenges with SHIV, the authors report. A total of 24 animals were divided into three groups; two that received one dose of GS-CA1 (either 150 or 300 mg per kg body weight) and a third, control group. The animals received weekly SHIV challenges for 15 weeks. All macaques in the highest dose of GS-CA1 group had no detectable virus in the plasma by week 17, 5 of which remained free of detectable virus by the end of the study period (24 weeks). The 300 mg per kg dose of GS-CA1 reduced the risk of infection by 97% per exposure.
GS-CA1 has a similar structure to another HIV capsid inhibitor called lenacapavir, which has shown promising antiviral activity in clinical trials. The results of GS-CA1 treatment in nonhuman primates may help to guide further clinical trials of these HIV capsid inhibitors to determine for how long a single dose might offer protection, the authors note.
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