For patients with treated HIV who have or who are at an increased risk for atherosclerotic cardiovascular disease (ASCVD), low-dose methotrexate (LDMTX) does not significantly affect endothelial function or inflammatory biomarkers, according to results published in Clinical Infectious Diseases.
LDMTX was, however, associated with a significant reduction in CD8+ T cells.
The study included participants with treated HIV who were ≥40 years old with CD4+ T cells ≥400 cells/mm3 and with/at increased risk for ASCVD (n=176). Participants were randomly assigned to LDMTX (5 to 15 mg/week) or placebo (folic acid) for 24 weeks and were followed for an additional 12 weeks. The primary end points were safety and brachial artery flow-mediated dilation.
Of 176 participants, 86 were randomly assigned to LDMTX, and 90 were randomly assigned to placebo.
The researchers found that LDMTX was associated with reductions in CD4+ T cells at week 24 compared with placebo (P =.016). LDMTX was also associated with reductions in CD8+ T cells at weeks 8, 12, and 24 compared with placebo (P =.001).
In the LDMTX group, the change in flow-mediated dilation at week 24 was 0.47% compared with 0.09% for placebo (P =.55). The LDMTX group did not have any changes in inflammatory markers compared with those receiving placebo.
In the LDMTX group, 12.8% (n=11) of participants reported adverse events compared with 5.6% (n=5) in the placebo group. The most commonly reported events were infections, including 7 cases of pneumonia (4 in the LDMTX and 3 in the placebo group), 3 confirmed CD4+ T-cell declines of ≥50% (all in the LDMTX group), 2 Centers for Disease Control and Prevention category C events (both recurrent pneumonia, 1 in each group), 2 treatment-limiting toxicities (1 in each group), and 2 pulmonary toxicities (severe cough, both in the LDMTX group).
“The balance of risks and potential benefits of LDMTX on ASCVD risk in the setting of treated and suppressed HIV infection remains unclear and will require additional investigation,” the researchers wrote.
Disclosures: Multiple study authors report relationships with the pharmaceutical industry. Please refer to original text for full list of authors’ disclosures.
Hsue PY, Ribaudo HJ, Deeks SG, et al. Safety and impact of low-dose methotrexate on endothelial function and inflammation in individuals with treated human immunodeficiency virus: AIDS Clinical Trials Group Study A5314 [published online September 14, 2018]. Clin Infect Dis. doi:10.1093/cid/ciy781