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One Penicillin Dose as Good as Three for Early Syphilis in Men With HIV
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51st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), September 17-20, 2011, Chicago
Mark Mascolini
One dose of benzathine penicillin worked as well as three for early syphilis in a nonrandomized comparison of 330 HIV-positive men in Taiwan [1]. Men with a CD4 count above 350 and secondary syphilis had higher penicillin response rates.
US opportunistic infection guidelines for people with HIV call for a single intramuscular 2.4-million-unit dose of benzathine penicillin G for early (primary, secondary, or early-latent) syphilis [2]. "Although most HIV-infected persons with early syphilis respond appropriately to standard benzathine penicillin," these guidelines note, "some specialists recommend two additional weekly benzathine penicillin injections. The benefit of this treatment approach remains unproven."
To assess the relative effectiveness of one versus three penicillin doses for early syphilis, researchers in Taiwan planned this prospective observational comparison of HIV-positive men with early syphilis recruited at seven hospitals. All men had rapid plasma reagin (RPR) titers at or above 4. The study excluded men treated for syphilis in the past 12 months.
The investigators tracked response to penicillin by monitoring RPR titers every 3 months after treatment began. They defined treatment failure as (1) failure to achieve a 4-fold or greater drop in RPR titer after 12 months of follow-up or (2) a 4-fold or greater RPR increase after achieving a 4-fold decline. The analysis included patients who completed at least 6 months of follow-up. To compare results with one versus three doses, the investigators used a last-observation-carried-forward analysis.
The study involved 330 HIV-positive men with an average age of 33.1 years who enrolled between January 2007 and March 2011, including 35 (10.6%) with primary syphilis, 228 (69.1%) with secondary syphilis, and 67 (20.3%) with early-latent syphilis. There were 105 men (31.8%) with a history of syphilis, and 185 (56.1%) were taking combination antiretroviral therapy.
Of the 330 study participants, 150 (45.5%) got one penicillin shot and 180 (54.5%) got three. Clinical characteristics of the two groups did not differ substantially. CD4 counts averaged 466 in the one-dose group and 441 in the three-dose group. Respective viral loads averaged 3.20 and 3.24 log10 copies/mL (about 2000 copies). Despite these similarities, the nonrandomized nature of the study leaves open the possibility that undetermined factors influenced response.
After 6 months of follow-up, response rates were 74.0% in the single-dose group and 65.6% in the three-dose group. Twelve-month response rates were 79.7% with one dose and 74.5% with three.
Three factors affected chances of serologic response: primary syphilis (7.7% of responders versus 17.7% of nonresponders, P = 0.051), secondary syphilis (75.2% of responders versus 61.3% of nonresponders, P = 0.037), and a CD4 count at or below 350 (34.0% of responders versus 53.2% of nonresponders, P = 0.011).
References
1. Chen T, Wu H, Lee N, et al. Comparison of effectiveness of 1 dose versus 3 doses of benzathine penicillin in treatment of early syphilis in HIV-infected patients: multicenter, prospective observational study. 51st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). September 17-20, 2011. Chicago. Abstract L2-892.
2. CDC, National Institutes of Health, HIV Medicine Association of the Infectious Diseases Society of America. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents. Morbidity and Mortality Weekly Report. April 10, 2009. Vol. 58, No. RR-4. http://www.cdc.gov/mmwr/pdf/rr/rr5804.pdf.
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