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Monoclonal Antibody to IL-1beta Cuts Arterial Inflammation in 10 HIV Patients
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Conference on Retroviruses and Opportunistic Infections (CROI), February 13-16, 2017, Seattle
Mark Mascolini
A single subcutaneous injection of canakinumab, a monoclonal antibody to the inflammation driver IL-1beta, lowered inflammation in arteries of 10 people taking suppressive antiretroviral therapy (ART) [1]. A placebo-controlled trial of canakinumab in adults with HIV is recruiting participants [2].
Inflammation-driven atherosclerosis has emerged as a complication of well-controlled HIV infection. University of California, San Francisco investigators who conducted the new study note that IL-1 lies at an early point on the pathway to inflammation. By binding to the IL-1 receptor, IL-1beta stimulates atherogenesis. Canakinumab is a human monoclonal IL-1beta antibody licensed for treatment of inflammatory disorders. By binding to IL-1beta, 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 < 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 [2]. Participants must be 40 or older and must have a CD4 count of at least 400 and an undetectable viral load for 52 weeks.
References
1. Hsue P, Deeks SG, Isha AE, et al. IL-1beta inhibition significantly reduces atherosclerotic inflammation in treated HIV. Conference on Retroviruses and Opportunistic Infections (CROI), February 13-16, 2017, Seattle. Abstract 126. http://www.croiconference.org/sessions/il-1%CE%B2-inhibition-significantly-reduces-atherosclerotic-inflammation-treated-hiv
2. ClinicalTrials.gov. Effect of IL-1beta inhibition on inflammation and cardiovascular risk. ClinicalTrials.gov identifier NCT02272946. https://clinicaltrials.gov/ct2/show/NCT02272946
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