Should syphilis be treated differently in HIV-positive and HIV-negative individuals? Treatment outcomes at a university hospital,Brighton,UK

INTRODUCTION

There has been much debate regarding optimum treatment for syphilis in HIV-positive patients and whether this should be different from HIV-negative individuals. The Centers for Disease Control and Prevention guidelines currently recommend a single dose of intramuscular benzathine penicillin G (BP) for early syphilis regardless of HIV status. ¹ The British Association of Sexual Health and HIV, HIV Specialist Interest Group previously recommended treating early syphilis in HIV-positive individuals with a neurosyphilis regimen ² (i.e. intramuscular procaine penicillin for 17 days with oral probenecid 500 mg qds) because of the significant treatment failure and neurological relapse rate using BP. ^3–6 BP in immunocompetent patients, with an intact host immune response, is an adequate treatment despite its failure to reach treponemocidal concentrations in the cerebrospinal fluid. ⁷

Recently, there has been a shift in expert opinion in the UK and it has been suggested that ‘2 doses of Benzathine penicillin G one week apart is adequate treatment in HIV-positive people who are not profoundly immunosuppressed’, provided follow-up can be guaranteed. ⁸ In practice, as described by Ghanem et al. ⁹ in 2006, adequate follow-up of patients with syphilis can be challenging. Of their HIV-positive cohort, 64% had no documented syphilis serology following treatment. There is little data informing clinicians on how to predict which patients have asymptomatic neurosyphilis and require a neurosyphilis treatment regimen. ¹⁰

Furthermore, in this patient group it may be particularly difficult to differentiate future neurological abnormalities related to HIV from manifestations of neurosyphilis. In this treatment centre (where there has been a syphilis outbreak since 1999), ¹¹ HIV-positive patients or those of unknown HIV status were recommended treatment with intramuscular procaine penicillin and oral probenecid (PP) for 17 days, whereas those known to be HIV negative were treated with two doses of BP.

METHODS

Data on patients diagnosed with early syphilis (using EIA/TPHA and VDRL) between July 1999 and July 2006 were collected prospectively, including demographics, date of syphilis diagnosis, stage of syphilis, HIV status, syphilis treatment given and completion, and serological follow-up. Completion of the initial or second treatment regimen (in the case of treatment switch) was recorded. As in other studies, ¹² treatment success was defined as a two dilution (four-fold) or greater decrease in the Venereal Disease Research Laboratory (VDRL) or achievement of a negative VDRL within six months of treatment. CSF examination was not carried out routinely. Chi-square without Yates correction was used for statistical analyses.

RESULTS

A total of 350 cases of early syphilis were diagnosed during the study period; 92% were in homosexual men. In all, 37% were HIV positive, 57% were HIV negative and 6% declined testing. Those with HIV were less likely to have symptomatic syphilis (62% versus.73%, P = 0.03) (Table 1). Eleven percent of patients were prescribed doxycycline because of penicillin allergy (after declining penicillin desensitization or before penicillin desensitization became part of clinical guidelines) or patient choice (refusal of injections). Of those completing the treatment, over 98% of HIV-positive patients were followed up to at least six months and met the criteria for treatment success. One treatment failure occurred in a patient treated with PP and one treated with BP. In each case, it was not possible to exclude re-infection. Three HIV-negative patients and one with unknown HIV status failed to have a successful serological response.

In all other patients followed up to 12 months, there were no serological or clinical relapses.

DISCUSSION

The syphilis outbreak in Brighton is similar to those reported elsewhere, ¹³ i.e. predominantly among men who have sex with men, of whom a significant proportion are HIV positive. Asymptomatic disease is seen more commonly in HIV-positive individuals presumably secondary to regular syphilis screening as part of routine care. ¹⁴

While some practitioners and patients consider a 17-day regimen of PP to be ‘excessive’, ⁸ we consider that it is currently unclear how to define patients who require an extended course of treatment. ^10,15 With an explanation of the rationale for enhanced treatment in HIV, we have demonstrated that patients adhere well to this regimen.

Follow-up of HIV-positive patients completing syphilis treatment in our centre, where both HIV and STIs are managed together, is good and better than that of HIV-negative individuals. Once HIV-negative patients had a treatment response consistent with treatment success, many did not return for further follow-up serology despite recall. HIV-positive patients had repeat syphilis serology as part of their routine HIV care, resulting in high long-term follow-up rates.

Most importantly, we have shown rates of treatment success in HIV-positive individuals comparable (or indeed superior) to those without HIV in numbers greater than those reported in the published literature. ^3,9

Although these data are observational and uncontrolled, we believe that our results suggest that there is sufficient equipoise to challenge current guidelines ⁸ and that a further prospective randomized trial of routine (i.e. benzathine) therapy versus enhanced (e.g. procaine) treatment is needed in HIV-positive individuals with early syphilis.