Higher Serologic Responses of Early Syphilis to Single-dose Benzathine Penicillin G Plus Doxycycline Versus Single-dose Benzathine Penicillin G Alone Among People With HIV.

Background: Single-dose benzathine penicillin G (BPG) is the preferred therapy for early syphilis, but poorer serologic responses have been observed among people with human immunodeficiency virus (PWH). No enhanced regimen has previously been shown to improve serologic outcomes of early syphilis.

Methods: We conducted a retrospective study to compare the treatment responses to single-dose BPG combined with 7-day doxycycline versus BPG alone in PWH who presented with early syphilis. Rapid plasma reagin (RPR) titers were determined every 3-6 months for all included PWH. Serologic response was defined as at least a 4-fold decline in RPR titers at month 12.

Results: During January 2018 to March 2022, 223 PWH with 307 episodes of early syphilis received single-dose BPG plus doxycycline and 347 PWH with 391 episodes received BPG alone. The median age was 36 years and baseline CD4 count was 600 cells/mm3. In the intention-to-treat with last-observation-carried-forward analysis, PWH receiving BPG plus doxycycline had a significantly higher serologic response rate at 12 months of treatment than those receiving BPG alone (79.5% vs 70.3%, respectively; P = .006). The factors associated with 12-month serologic response were RPR titer (per 1-log2 increase, adjusted odds ratio [AOR], 1.25; 95% confidence interval [CI], 1.15-1.35) and receipt of BPG plus doxycycline (AOR, 1.71; 95% CI, 1.20-2.46). In the subgroup analyses, BPG plus doxycycline was consistently associated with a better serologic response than BPG alone at month 12.

Conclusions: Among PWH with early syphilis, single-dose BPG plus doxycycline achieved higher serologic responses than BPG alone during a 12-month follow-up period.