Low-dose methotrexate (LDMTX) does not improve arterial function in people living with HIV (PLWH) who are at risk for artherosclerotic cardiovascular disease (ASCVD), a phase II trial published in Clinical Infectious Diseases found.
The trial randomized 176 PLWH age 40 or older who had ASCVD or were at risk for it to the study drug or a placebo. All participants were on antiretroviral treatment, with a baseline CD4 cell count of at least 400 cells/mm3 (median CD4 count was 726 cells/mm3). Participants were mostly male (90%), but the cohort was racially diverse: 42% were white, 42% black, and 15% Latinx.
The drug or placebo were administered for 24 weeks and follow-up continued for 12 weeks thereafter. Rates of brachial artery flow-mediated dilation and hyperemic flow velocity -- measures of arterial function -- were unchanged in both groups. Safety events (particularly a large CD4 count drop) were more likely to occur among participants receiving LDMTX, but such events were uncommon overall, and the difference fell within the study's non-inferiority margin.
Standard anti-inflammatory treatments, such as statins, pentoxifylline, aspirin and hydroxychloroquine, have previously been shown to have little effect in PLWH, study authors noted. They hypothesized that T-cell abnormalities related to HIV itself may be stronger than methotrexate, thus mitigating the effect of the medication. Further study is warranted, they concluded.