Clinical and Serologic Baseline and Follow-Up Features of Syphilis According to HIV Status in the Post-HAART Era David Farhi, MD, Nadjet Benhaddou, MD, Philippe Grange, PhD, Nada Zizi, MD, Jean Deleuze, MD, Jean-Pierre Morini, MD, Philippe Gerhardt, MD, Anne Krivine, MD, Marie-Fran 0 oise Avril, MD, and Nicolas Dupin, MD, PhD Abstract: There is a lack of large studies appraising the effect of the human immunodeficiency virus (HIV) on the course of syphilis since the advent of highly active antiretroviral therapy (HAART). We aimed to appraise the effect of HIVon clinical and serologic features of syphilis at baseline and during follow-up in the post-HAART era. We designed a retrospective cohort study of consecutive syphilis cases, diagnosed between 2000 and 2007, in an academic venereal dis- ease center. Data were collected using standardized medical forms. Patients were treated according to the European guidelines. Serologic failure was defined as either a 4-fold rise in Venereal Disease Research Laboratory (VDRL) titers 30Y400 days posttreatment or a lack of 4-fold drop in VDRL titers at 270Y400 days posttreatment. Among 279 syphilis cases with informative baseline clinical and serologic data, HIV infection was significantly associated with men having sex with men, French origin, multiple partners, lesser usage of condom, history of sexually transmitted disease, early syphilis, anal primary chancre, and cutaneous eruption. Median baseline titer from the Treponema pallidum hemagglutination assay (TPHA) was higher in HIV-infected patients (p = 0.02). Among 144 informative syphilis cases, there was a nonsignificant trend for a lower rate of serologic response among HIV-positive patients (91.8% vs. 98.3%, p = 0.14). Serologic failure was significantly as- sociated with a history of previous syphilis (p G 0.05). The median delay to serologic response was similar in HIV-positive (117 d) and in HIV-negative (123 d) patients (p = 0.44). We conclude that for patients under HAART treatment, the effect of HIV on serologic response to syphilis treatment is likely minimal or absent. (Medicine 2009;88: 331Y340) Abbreviations: CSF = cerebrospinal fluid, FTA-abs = fluorescent treponemal antibody absorption test, HAART = highly active antiretroviral therapy, HIV = human immunodeficiency virus, HR = hazard ratio, MSM = men having sex with men, RPR = rapid plasma reagin, STD = sexually transmitted disease, TPHA = Treponema pallidum hemagglutination assay, VDRL = Venereal Disease Research Laboratory. INTRODUCTION A fter an all-time low during the 1990s, the incidence of syphilis is rising again in developed countries. 19,25 Since the early years of the human immunodeficiency virus (HIV) pan- demic, the multiple aspects of the association between syphilis and HIV have been the subject of a large number of publications. However, the extent to which HIV may modify the course of syphilis remains controversial. The rationale to expect an interaction between the 2 dis- eases is based on several epidemiologic and biological facts. First, syphilis and HIV infection are prone to occur concomi- tantly. HIV infection rates of up to 50% have been reported among patients diagnosed with syphilis in several regions, with higher HIV infection rates among men having sex with men (MSM). 5,17,38 HIV and syphilis share modes of acquisition and risk factors, including MSM, sexual workers, intravenous drug users, previous history of sexually transmitted diseases (STDs), and multiple partners. Proposed mechanisms for the increased HIV transmission associated with syphilis ulcers 10,34,37 include the tegument disruption; 4,6,11,29 as well as the high concentration of CD4 + cells 23 (which constitute target cells for HIV); and the effect of treponemal lipoproteins, including NTp47, that up- regulate HIV replication. 36 Second, experimental data support the importance of cell- mediated immune response in syphilis. 23 HIV infection impairs essentially cell-mediated immune response, and thus may pro- mote more severe forms of syphilis, as well as treatment failure. Moreover, HIValso impairs serologic response to several infec- tious agents. 1,24 Thus, HIV infection may alter the clinical pre- sentation, serologic response, and treatment outcome in patients with syphilis. During the pre-HIV era, reported rates of seroreversion were close to 100%. 8,9,28 However, treatment schedules in those studies were not always in agreement with current guidelines. Following the publication in the late 1980s of isolated cases of atypical clinical and laboratory features of syphilis in HIV- infected patients, 2,30 several researchers performed comparative studies of the clinical presentation, the serologic response, and the treatment outcome of syphilis according to HIV status, yielding conflicting results. 12,14,18,20Y22,26,27,31Y33,35,39 Whatever its true clinical importance, the interaction be- tween syphilis and HIV should always be considered as a dynamic concept, susceptible to change through succeeding therapeutic eras. Indeed, the emergence of highly active anti- retroviral therapy (HAART) in 1996 has deeply changed the clinical and biological impact of HIV infection. For instance, in a large observational clinical cohort of HIV-infected patients, Ghanem et al 13 recently demonstrated that the use of HAART may reduce syphilis failure rates among HIV-infected patients who have syphilis. Thus, in a historical perspective, studies appraising syphilis treatment outcome should be classified in 3 therapeutic eras: 1) the pre-HIV era, 2) the post-HIV Medicine & Volume 88, Number 6, November 2009 www.md-journal.com 331 From Department of Dermatology and Venereology (DF, NZ, JD, JPM, PG, MFA, ND), Ho ˆpital Cochin-Pavillon Tarnier, AP-HP, Universite ´ Paris 5-Rene ´ Descartes, Paris; Department of Bacteriology (NB), Ho ˆpital Cochin, AP-HP, Universite ´ Paris 5, Paris; Laboratoire de Recherche en Dermatologie et Centre National de Re ´fe ´rence de la Syphilis (PG, ND), UPRES EA 1833, Universite ´ Paris 5-Rene ´ Descartes, Paris; Department of Virology (AK), Ho ˆpital Saint-Vincent de Paul, AP-HP, Universite ´ Paris 5, Paris, France. Received July 11, 2009, and in revised form September 21, 2009. Accepted for publication September 23, 2009. Reprints: David Farhi, MD, Dermatology Clinic, 64 Avenue des Gobelins, 75013 Paris, France (e-mail: farhidavid)yahoo.fr). Copyright * 2009 by Lippincott Williams & Wilkins ISSN: 0025-7974 DOI: 10.1097/MD.0b013e3181c2af86 9 Copyright @ 200 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.