Safety and Effectiveness of Low-Dose Methotrexate for Reducing Inflammation in HIV-Infected Adults on ARV Medications

HIV-infected people taking ART have a higher than expected risk of premature CVD. Many factors likely contribute to this risk, including chronic inflammation. Strategies to reduce inflammation in HIV-infected people may be beneficial in reducing CVD risk, as well as other conditions, including kidney disease, bone disease, and neurologic complications. MTX is an anti-inflammatory medication used to treat people with rheumatoid arthritis. This study evaluated the safety and effectiveness of LDMTX at treating inflammation and on endothelial function in virologically suppressed HIV-infected adults who had CVD or were at increased risk of CVD. The total study duration was 36 weeks. Prior to enrolling in the study, participants had a chest X-ray. Participants were randomly assigned to receive LDMTX or placebo for 24 weeks. Participants continued taking their antiretroviral (ARV) medications as usual; ARVs were not provided by the study. At study entry, participants underwent a medical and medication history, physical examination, blood collection, and adherence assessments. From study entry through Week 1, participants received either 5 mg of LDMTX or placebo once a week. For participants who were clinically stable at the Week 1 study visit, the dose of LDMTX or placebo was increased to 10 mg once a week through Week 12. For participants who were clinically stable at the Week 12 study visit, the dose of LDMTX or placebo was increased to 15 mg once a week through Week 24. Participants who did not meet the criteria for dose escalation were re-evaluated at the following study visit. In addition to LDMTX or placebo, all participants also received 1 mg of folic acid once a day from study entry throughout Week 24. After taking the final dose of LDMTX or placebo, all participants continued taking folic acid for an additional 4 weeks. Post-entry visits occurred at Weeks 1, 2, 4, 8, 12, 18, 24, and 36. These included a physical examination, blood collection, and adherence assessments; an arm ultrasound test was performed at Weeks 12 and 24. At Week 2, some participants took part in a pharmacokinetic (PK) assessment, which involved undergoing a blood collection several times over a 6-hour period.