Antiretroviral therapy is associated with reduced serologic failure rates for syphilis among HIV-infected patients

Abstract

Background: Syphilis and human immunodeficiency virus (HIV) frequently coexist in patients, but the effects of immunosuppression on the course of syphilis are unknown. Our goal was to determine whether the degree of HIV-mediated immunosuppression and the use of highly active antiretroviral therapy impact syphilis serologic responses.

Methods: We assessed all cases of syphilis with positive serologic test results from 1990 through 2006 in a prospective, observational clinical cohort of HIV-infected patients. We defined seroreversion as the loss of reactivity in a patient who previously had a serologic test result positive for syphilis. We defined serologic failure as the lack of a 4-fold decrease in rapid plasma reagin titers 270-365 days after therapy or a 4-fold increase in titers > or =30 days after therapy. We used Cox proportional hazards models with statistical adjustments for multiple failure instances.

Results: One hundred eighty subjects experienced 231 cases of syphilis. The median follow-up time was 5.3 years. A total of 71 episodes of serologic failure were documented. A CD4 cell count of <200 cells/mL at the time of syphilis diagnosis was associated with an increased risk of serologic failure (adjusted hazard ratio, 2.48; 95% confidence interval, 1.26-4.88). The receipt of highly active antiretroviral therapy was associated with a 60% reduction in the rate of serologic failure (adjusted hazard ratio, 0.40; 95% confidence interval, 0.21-0.75), independent of concomitant CD4 cell response. Rapid plasma reagin seroreversion was infrequent (16.1%) and inconsistent, and it was more likely to occur among patients who received macrolides.

Conclusion: The use of highly active antiretroviral therapy to reverse immunosuppression and the routine use of macrolides for the prevention of opportunistic infections may reduce syphilis serologic failure rates among HIV-infected patients who have syphilis.

Figure 1

Probability of first rapid plasma reagin (RPR) seroreversion, by syphilis stage, among 180 patients. Follow-up time begins on the date of syphilis therapy and ends at the first documented time of RPR reversion; lines representing 95% CIs are provided.

Figure 2

Example of a patient who experienced posttreatment rapid plasma reagin (RPR) seroreversion with evidence of fluctuating titers; therapy was given at the time of diagnosis. Twenty-three (88.5%) of 26 patients who had evidence of RPR seroreversion exhibited a similar course.