Comparison of Serological Response to Doxycycline versus Benzathine Penicillin G in the Treatment of Early Syphilis in HIV-Infected Patients: A Multi-Center Observational Study Jen-Chih Tsai 1,2 , Yu-Huei Lin 3 , Po-Liang Lu 4 , Ni-Jiin Shen 1,5 , Chia-Jui Yang 6 , Nan-Yao Lee 7 , Hung- Jen Tang 8 , Yuag-Meng Liu 9 , Wen-Chi Huang 10 , Chen-Hsiang Lee 10 , Wen-Chien Ko 7 , Yen-Hsu Chen 4 , Hsi- Hsun Lin 11 , Tun-Chieh Chen 4,12 *, Chien-Ching Hung 1,13,14 * 1 Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan, 2 Department of Internal Medicine, Tzu-Chi Hospital and Tzu-Chi University College of Medicine, Hua-Lien, Taiwan, 3 Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan, 4 Department of Internal Medicine, Kaohsiung Medical University Hospital and College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, 5 Department of Internal Medicine, National Taiwan University Hospital Yun-Lin Branch, Yun-Lin, Taiwan, 6 Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan, 7 Department of Internal Medicine, National Cheng Kung University College of Medicine and Hospital, Tainan, Taiwan, 8 Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan, 9 Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan, 10 Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan, 11 Department of Internal Medicine, E-Da Hospital/ I-Shou University, Kaohsiung, Taiwan, 12 Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, 13 Department of Medical Research, China Medical University Hospital, Taichung, Taiwan, 14 China Medical University, Taichung, Taiwan Abstract Background: While doxycycline is recommended as an alternative treatment of syphilis in patients with penicillin allergy or intolerance, clinical studies to compare serological response to doxycycline versus benzathine penicillin in treatment of early syphilis among HIV-infected patients remain sparse. Methods: We retrospectively reviewed the medical records of HIV-infected patients with early syphilis who received doxycycline 100 mg twice daily for 14 days (doxycycline group) and those who received 1 dose of benzathine penicillin (2.4 million units) (penicillin group) between 2007 and 2013. Serological responses defined as a decline of rapid plasma reagin titer by 4-fold or greater at 6 and 12 months of treatment were compared between the two groups. Results: During the study period, 123 and 271 patients in the doxycycline and penicillin group, respectively, completed 6 months or longer follow-up. Ninety-one and 271 patients in the doxycycline and penicillin group, respectively, completed 12 months or longer follow-up. Clinical characteristics were similar between the two groups, except that, compared with penicillin group, doxycycline group had a lower proportion of patients with secondary syphilis (65.4% versus 41.5%, P, 0.0001) and a higher proportion of patients with early latent syphilis (25.3% versus 49.6%, P,0.0001). No statistically significant differences were found in the serological response rates to doxycycline versus benzathine penicillin at 6 months (63.4% versus 72.3%, P = 0.075) and 12 months of treatment (65.9% versus 68.3%, P = 0.681). In multivariate analysis, secondary syphilis, but not treatment regimen, was consistently associated with serological response at 6 and 12 months of follow-up. Conclusions: The serological response rates to a 14-day course of doxycycline and a single dose of benzathine penicillin were similar in HIV-infected patients with early syphilis at 6 and 12 months of follow-up. Patients with secondary syphilis were more likely to achieve serological response than those with other stages. Citation: Tsai J-C, Lin Y-H, Lu P-L, Shen N-J, Yang C-J, et al. (2014) Comparison of Serological Response to Doxycycline versus Benzathine Penicillin G in the Treatment of Early Syphilis in HIV-Infected Patients: A Multi-Center Observational Study. PLoS ONE 9(10): e109813. doi:10.1371/journal.pone.0109813 Editor: Roberto F. Speck, University Hospital Zurich, Switzerland Received April 9, 2014; Accepted September 1, 2014; Published October 13, 2014 Copyright: ß 2014 Tsai et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability: The authors confirm that, for approved reasons, some access restrictions apply to the data underlying the findings. The relevant data will be made fully available without restriction after decoding and approval by the respective Research Ethics Committee of each participating hospital. Requests for data may be sent to the corresponding author. Funding: This study was supported by a grant from the Centers for Disease Control, Taiwan (grant number DOH102-DC-1401 to C.-C. H.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * Email: dalechen.chen@gmail.com (T-CC); hcc0401@ntu.edu.tw (C-CH) PLOS ONE | www.plosone.org 1 October 2014 | Volume 9 | Issue 10 | e109813