Lenacapavir demonstrates efficacy in people with highly resistant HIV

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Lenacapavir, an experimental HIV capsid inhibitor, led to rapid viral load reduction in highly treatment-experienced people with multidrug-resistant virus, according to a study presented at the virtual Conference on Retroviruses and Opportunistic Infections (CROI 2021).

Aidsmap reports that what's more, lenacapavir's long half-life in the body suggests it has the potential to be a component of long-acting antiretroviral regimens taken every six months or to be used alone as long-acting PrEP (regular medication to prevent HIV infection).

Lenacapavir (formerly known as GS-6207), from Gilead Sciences, disrupts the HIV capsid, the cone-shaped shell that surrounds the viral genetic material and essential enzymes. Laboratory studies showed that it interferes with multiple stages of the HIV lifecycle. Because it works differently to existing drugs, it remains active against virus that has developed resistance to other antiretroviral classes. Prior research showed that a single dose led to sustained drug concentrations for several months.

Aidsmap reports that Professor Sorana Segal-Maurer of New York-Presbyterian Queens Hospital presented findings from the phase II/III CAPELLA trial, which enrolled 72 people with resistance to at least two drugs from three of the four major antiretroviral classes. About 75% were men and the median age was 52 years. They were currently on antiretroviral therapy but were unable to maintain viral suppression; the mean baseline viral load was over 4 log10. About two thirds had advanced immune suppression with a CD4 count below 200.

The report says in a related study, Dr Justin Lutz of Gilead and colleagues assessed drug-drug interactions between oral lenacapavir and other medications. The results showed that lenacapavir can be used with strong inhibitors of the CYP3A and P-glycoprotein drug metabolism pathways, but should not be used with potent CYP3A and P-glycoprotein inducers or UGT1A1 inhibitors. Overall, the researchers concluded, lenacapavir has "limited drug interaction potential."

Based on these findings, the researchers concluded that lenacapavir could become an important agent for heavily treatment-experienced people with multidrug-resistant HIV.

The results are "really encouraging," Segal-Maurer is quoted in Aidsmap as saying.

 

Full Aidsmap report (Open access)

 

CROI 2021 study

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