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Canakinumab, a monoclonal antibody to IL-1 beta, cuts arterial inflammation in HIV patients


A single subcutaneous injection of Canakinumab, a monoclonal antibody to the inflammation driver IL-1 beta, lowered inflammation in arteries of 10 people taking suppressive antiretroviral therapy ( ART ).
A placebo-controlled trial of Canakinumab in adults with HIV is recruiting participants.

Inflammation-driven atherosclerosis has emerged as a complication of well-controlled HIV infection.

University of California, San Francisco ( UCSF ) researchers who conducted the new study have noted that IL-1 lies at an early point on the pathway to inflammation. IL-1 beta stimulates atherogenesis.

Canakinumab ( Ilaris ) is a human monoclonal IL-1 beta antibody licensed for treatment of inflammatory disorders. By binding to IL-1 beta, the antibody rapidly inhibits inflammation with a minimal impact on lipids.

This open-label single-arm study recruited HIV-positive people at least 40 years old, taking suppressive ART, and having established cardiovascular disease or at least one cardiovascular risk factor.

All participants received a single 150-mg subcutaneous dose of Canakinumab.

The researchers measured inflammatory markers and immune activation before and 8 weeks after Canakinumab dosing.
They used fluorodeoxyglucose positron emission tomography ( FDG-PET ) before and 8 weeks after dosing to gauge atherosclerotic arterial inflammation.
The radiologist who read the FDG-PET scans did not know whether they were pre- or posttreatment scans.

Ten participants, 9 of them men, had a median age of 59 ( interquartile range [ IQR ] 55 to 65 ), a median CD4 count of 638 ( IQR 570 to 1142 ), and a median HIV duration of 24 years ( IQR 22 to 27 ).
All were on ART with an undetectable viral load.
Eight participants were taking a statin, 4 had a family history of cardiovascular disease, and 3 already had a myocardial infarction or stroke.

Absolute neutrophil count dropped by 28% at weeks 2 and 3 then rebounded at week 4. CD4 count and viral load did not change during the study. One case of shingles developed and resolved.

IL-6 and hsCRP, two inflammation markers, declined significantly ( by 30% 41% ) from baseline to week 8 ( P = 0.003 and 0.039 ).
sCD163, a marker of inflammation and cell activation, fell 9% from baseline to week 8 ( P = 0.015 ).

FDG-PET scans showed significantly reduced arterial ( aortic ) inflammation and bone marrow activity.
Arterial inflammation dropped 10% ( P = 0.046 ), while bone marrow metabolic activity fell by 11% ( P less than 0.001 ).

The placebo-controlled trial aims to recruit 100 people and randomize them 2-to-1 to two 150-mg doses of Canakinumab separated by 12 weeks or to placebo.
Participants must be 40 or older and must have a CD4 count of at least 400 and an undetectable viral load for 52 weeks. ( Xagena )

Source: Conference on Retroviruses and Opportunistic Infections ( CROI ), 2017

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