Penicillin or Ceftriaxone for Neurosyphilis in People With HIV: A Retrospective, Propensity Score-Matched Multicenter...

Neurosyphilis, ocular syphilis, and otosyphilis occur more frequently among people with HIV-1 and are associated with higher morbidity and treatment failure. Intravenous penicillin G remains the standard therapy but requires hospitalization or prolonged intravenous access, creating barriers that are amplified in resource-limited settings facing recurrent penicillin shortages. Ceftriaxone is a potential alternative; however, comparative data in people with HIV are limited.

We conducted a multicenter retrospective cohort study of adults with HIV at 5 public hospitals and 2 outpatient HIV clinics in Mexico (2015-2024). Participants had confirmed neurosyphilis, ocular syphilis, or otosyphilis. Participants received intravenous penicillin G (18-24 million IU/day) or ceftriaxone (1-2 g/day) for 10-14 days. The primary outcome was early serological response (ESR), defined as a ≥4-fold nontreponemal titer decline or seroreversion at 6 months. We performed 1:1 propensity score matching (39 pairs, n = 78), followed by logistic regression in the matched cohort.

Of 143 participants, 104 (73%) received intravenous penicillin G and 39 (27%) ceftriaxone. In the matched cohort, ESR occurred in 74.4% of penicillin-treated participants and 71.8% of ceftriaxone-treated participants (odds ratio 0.88, 95% confidence interval .32-2.40; P = .80). The results were consistent across all prespecified sensitivity analyses.

In this multicenter cohort of people with HIV diagnosed with neurosyphilis, ocular syphilis, or otosyphilis, ceftriaxone showed comparable ESR to intravenous penicillin G. These findings support ceftriaxone as a reasonable alternative when standard therapy is limited by penicillin shortages, limited inpatient capacity, or financial constraints.