Syphilis among individuals receiving CAB-LA for HIV prevention in Zambia

Syphilis remains an important public health concern among populations at high risk of HIV infection. Although long-acting injectable cabotegravir (CAB-LA) is highly effective for HIV prevention, limited evidence exists on syphilis burden among CAB-LA users in Zambia. This study examined baseline syphilis prevalence, follow-up incidence, geographic distribution, and factors associated with incident syphilis among individuals receiving CAB-LA for HIV prevention in Zambia. A retrospective cohort study was conducted using routinely collected programmatic data from 3,755 individuals initiated on CAB-LA across multiple provinces in Zambia during the national introduction period (October 2023–September 2024). Baseline syphilis prevalence was calculated among participants with valid baseline syphilis results. Incident syphilis was assessed among baseline non-reactive participants with at least one repeat syphilis test during follow-up. Poisson regression with person-time offset was used to estimate crude and adjusted incidence rate ratios (IRRs). Among 2,755 participants with valid baseline syphilis results, 126 tested reactive, giving a baseline prevalence of 4.57% (95% CI: 3.85–5.42). Baseline prevalence was highest in Copperbelt Province (11.36%), Northwestern (8.57%), and Western Province (7.27%). Participants reporting intimate partner violence had higher prevalence (8.70%) than those without IPV (4.51%), while alcohol users had higher prevalence (7.76%) than non-users (4.31%). During follow-up, only 1,318 participants had at least one repeat syphilis test, while 2,437 (65%) had no documented repeat test. Among 1,117 at-risk participants, 31 incident infections occurred, yielding a cumulative incidence of 2.78% (95% CI: 1.96–3.91) and an incidence rate of 11.76 per 100 person-years (95% CI: 7.99–16.69). Southern Province recorded the highest number of incident infections (21 cases; incidence rate: 14.50 per 100 person-years). In adjusted Poisson regression, Western Province was associated with higher incident syphilis (adjusted IRR: 6.24; 95% CI: 1.02–38.31; p=0.048), while sex, age, depression, IPV, and alcohol use were not statistically significant. Syphilis burden among CAB-LA users in Zambia remains substantial, with infections concentrated in high-mobility areas. The major programmatic gap was poor follow-up syphilis testing during CAB-LA care. Routine syphilis screening and treatment should be integrated into every CAB-LA visit, supported by strengthened STI monitoring systems, reliable benzathine penicillin supply, and targeted interventions in high-risk geographic areas.