HIV-infected individuals on antiretroviral therapy (ART) are at increased risk for
cardiovascular disease (CVD), likely due to chronically increased inflammation. Low-dose
methotrexate (LDMTX) may reduce CVD risk in people with rheumatoid arthritis, who like those
with HIV, have increased levels of inflammation. The NHLBI is funding a clinical trial
targeting the excess inflammation in HIV. That "Parent Study" is a randomized, double-blind,
placebo-controlled trial (NCT01949116) that will assess whether 24-week treatment with LDMTX:
i) is safe, ii) reduces circulating inflammatory biomarkers and levels of immune cell
activation and iii) improves brachial artery reactivity. However, neither the biomarkers nor
endothelial function tests measured as part of the parent study will report on
atherosclerotic inflammation, (the desired pathobiological target of LDMTX therapy in HIV).
As such, the direct evaluation of arterial inflammation would substantially enhance the
scientific value of the trial. In this imaging sub-study, the overall goal is to determine if
treating virologically suppressed, HIV-infected individuals with LDMTX will reduce
inflammation within the arterial wall.
This fully integrated ancillary study would, in a subset of patients enrolled in the parent
trial: (i) assess the impact of LDMTX on arterial inflammation, (ii) evaluate mechanisms
responsible for arterial inflammation in HIV and iii) explore mechanisms responsible for
actions of LDMTX on the artery wall. Accordingly, the proposed study would provide unique and
highly complementary information that would greatly increase the knowledge and mechanistic
insights gained from Parent Study. The ancillary study has two specific aims1) To determine
the impact of anti-inflammatory treatment with LDMTX on arterial inflammation, as assessed by
FDG-PET/CT imaging, in virally suppressed HIV-infected individuals., and 2) To evaluate the
cellular and biochemical basis of the effect of LDMTX therapy on arterial inflammation in
HIV.
Details
Lead Sponsor:
Massachusetts General Hospital
Collaborators:
Brigham and Women's Hospital Harvard School of Public Health Harvard School of Public Health (HSPH) University of California, San Francisco