Impact of HIV on disability progression in multiple sclerosis: An observational retrospective matched cohort study.

BACKGROUND: The coexistence of HIV infection and multiple sclerosis (MS) is uncommon, and poorly characterized. Whether HIV-related immune modulation influences MS, progression remains uncertain. Despite theoretical immunological interactions, real-world data are scarce. OBJECTIVES: To compare long-term disability outcomes in persons living with HIV (PLWHIVs) with MS (MS-PLWHIVs) versus matched HIV-negative MS controls (MS-controls). METHODS: This observational retrospective matched cohort study used databases from two French tertiary MS centers (1991-2021). Each MS-PLWHIV was matched with up to five MS-controls for MS subtype (relapsing-remitting or primary-progressive), sex, age at first MS attack (±5 years), and first-to-second attack interval (±5 years). The primary outcome was time to reach sustained EDSS-6 (cane use for≥12 months). Time-to-event analyses used Kaplan-Meier estimates and Cox regression adjusted for matching variables. RESULTS: We identified 16 MS-PLWHIVs and 75 matched MS-controls, with comparable baseline MS characteristics and a median follow-up>20 years. MS-PLWHIVs received significantly fewer MS disease-modifying therapies (MS-DMTs) (median: 0 [0-1] vs. 2 [1-3.5], P<0.001), and only 19% were still treated at study end versus 75% of controls. Notwithstanding this treatment gap, MS-PLWHIVs reached EDSS-6 a median of 8 years later than controls (22.8 vs. 14.5 years, P=0.05). However, the risk of reaching EDSS-6 did not differ significantly (adjusted HR: 1.60 [95% CI: 0.6-4.2], P=0.6). One-third of patients in each group converted to secondary progressive MS. CONCLUSION: Despite fewer MS-DMTs, MS-PLWHIVs did not show worse disability progression and even appeared to progress more slowly. While HIV-related immune modulation could contribute, this remains speculative. These findings, though limited by small sample size and retrospective design, provide rare long-term data on this understudied comorbidity.