Predictors of Serological Failure After Treatment in HIV-infected Persons with Early Syphilis

Background: In the emerging era of universal antiretroviral therapy (ART) use in HIV-infected patients, it is useful to know the predictive factors of serologic response after early syphilis treatment.

Methods: We performed a retrospective chart review of all cases of early syphilis with positive serologic test results in HIV-infected patients from May 2006 to May 2011 in 2 large, urban HIV clinics. Serologic failure was defined as a lack of 4-fold decrease in rapid plasma reagent (RPR) titers 9 to 12 months after syphilis treatment. Baseline characteristics including age, race, gender, syphilis stage (primary, secondary, early latent), baseline RPR titer, CD4 T-cell count, plasma HIV viral load, ART use, syphilis history, current amphetamine use, syphilis treatment type, and history of other sexually transmitted diseases were selected on a priori knowledge and tested independently and dependently as predictive factors of serologic failure using a univariate and multivariate logistic regression model, respectively.

Results: Of 560 patients with confirmed cases of syphilis, 486 (87%) were on ART.  A total of 51 patients (9.0%) experienced serologic failure.  Multivariate logistic regression modeling demonstrated that the predictive factors associated with serologic failure after early syphilis treatment were a CD4 T-cell count below 350 cells/ml (OR 2.41 [95%CI, 1.27- 4.56]), a previous history of syphilis (OR 3.12  [95%CI, 1.55- 6.26]), and baseline RPR titer ≤ 1:16 (OR 3.91[95%CI, 2.04- 7.47]), independent of other  characteristics.  Of note, type of syphilis treatment (1 dose versus 3 doses of benzathine penicillin) did not affect the proportion of serologic failure (2 % versus 10%, P = 0.25).

Conclusion: HIV-infected patients with a CD4 T-cell count <350 cells/ml, syphilis history, and/or baseline RPR titer ≤1:16 should be closely monitored for serologic failure after early syphilis treatment.  Treatment with > 1 dose of benzathine penicillin was not associated with decreased frequency of serologic failure, supporting the current recommendation that one dose of benzathine penicillin is adequate treatment for early syphilis in HIV-infected patients.