Elsevier

Clinics in Dermatology

Volume 28, Issue 5, September–October 2010, Pages 539-545
Clinics in Dermatology

Management of syphilis in the HIV-infected patient: Facts and controversies

https://doi.org/10.1016/j.clindermatol.2010.03.012Get rights and content

Abstract

After reaching an all time low at the turn of the millennium in several industrialized countries, the syphilis incidence is rising again, perhaps as a consequence of unsafe sexual behavior in response to improved antiretroviral therapeutic options for HIV. Since the beginning of the HIV pandemic, numerous reports on the various aspects of the interaction between syphilis and HIV have been published. Controversies persist on many issues of the management of coinfected patients. This contribution presents a critical appraisal of the available literature. Few large-scale, properly designed, controlled studies have compared syphilis baseline presentation and treatment response according to HIV status. Among the weakness are (1) high rates of patients lost to follow-up, (2) lack of long-term follow-up, (3) lack of gold standard criteria for treatment response, (4) small sample size, and (5) lack of stratification according to syphilis stage, ongoing antiretroviral treatment, CD4 cell count and HIV viral load. From the available data, and given the ever-possible publication bias, we conclude that if HIV has an effect on the course of syphilis, it is small and clinically manageable in most cases. The controversial issues discussed should furnish the rational for clinical research during the forthcoming decade.

Introduction

During the 1980s, changes in behavior in response to the HIV epidemic contributed to dramatic reductions in the syphilis incidence.1 After reaching an all time low at the turn of the millennium in several industrialized countries, the syphilis incidence is rising again,1, 2, 3, 4, 5, 6 perhaps as a consequence of unsafe sexual behavior in response to improved antiretroviral therapeutic options for HIV.7, 8

Numerous reports on the various aspects of the interaction between syphilis and HIV have been published since the beginning of the HIV pandemic. Controversies persist on many issues of the management of coinfected patients. We present a critical appraisal of the available literature. Syphilis and HIV have two levels of interactions: behavioral and biologic9; hence, this review is segmented into sections. First, we present the common epidemiologic features of syphilis and HIV, which will help clarify why these infectious diseases are likely to interact. Second, we review the available data on the potential biologic effects of syphilis on HIV. Third, the data on the biologic effects of HIV on syphilis are reviewed. Finally, we delineate potential areas of research.

Section snippets

Common epidemiologic features of syphilis and HIV

Syphilis and HIV have the same mode of acquisition and the same risk factors. Sexual workers, intravenous drug users, men having sex with men, patients with previous history of sexually transmitted disease (STD), and patients with multiple partners are at higher risk of acquisition of HIV, syphilis, and other STDs.

Since 2000, the incidence of syphilis is increasing among HIV-infected men having sex with men. Rates of HIV infection of up to 50% have been reported among patients diagnosed with

Increased risk of HIV

Syphilis infection increases the risk of transmission and acquisition of HIV infection.5, 9,8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 Chancres are risk factors for HIV acquisition,18, 21, 22 and HIV has been identified in primary syphilitic ulcers.23 This is not only related to the integument discontinuity represented by the chancre but also to biologic interactions.

Syphilis ulcerations are rich in CD4

Syphilis lesions are rich in macrophages and CD4+ T lymphocytes, which represent target-cells for the virus.24

Treponemal lipoproteins facilitate the bidirectional transmission of HIV

The

Effects of HIV on syphilis

Since the early years of HIV, many researchers studied the effect of HIV on the course of syphilis. Isolated case reports are subject to publication bias, however, and available epidemiologic studies should also be interpreted with caution given the frequent finding of one or more of the following weakness: (1) high rates of patients lost to follow-up, (2) lack of long-term follow-up, (3) lack of a gold standard criteria for treatment response, (4) small sample size, and (5) lack of

Does HIV modify the clinical presentation of syphilis?

The clinical and laboratory presentations of syphilis are similar in most patients with and without HIV infection.31 Since 1987, concern has been raised in several isolated case reports and small series,32, 33 and then in larger epidemiologic studies,34, 35, 36, 37 that syphilis in HIV-infected patients might be associated with a modified clinical presentation.

A retrospective study compared the clinical features of neurosyphilis according to HIV status. Neurosyphilis in 24 HIV-infected patients

Are HIV patients at higher risk of neurosyphilis?

During the late 1980s, several anecdotal cases of neurosyphilis after adequate treatment of early syphilis with a single dose of benzathine penicillin pointed out that HIV might be a risk factor for syphilis treatment failure and higher rates of neurosyphilis,32, 33 the conjunction of which has been termed “neurorecurrence.”29

Treponema pallidum (TP) invades the central nervous system in about 25% of patients,38 and abnormal CSF has been retrieved in up to 70% of patients with early syphilis.39

When to perform a lumbar puncture in HIV-infected patients with asymptomatic syphilis?

All major guidelines recommend a lumbar puncture in patients with syphilis who present with neurologic or ophthalmic signs or symptoms.11, 48, 49⁎49

As discussed earlier, whether HIV infected patients are at higher risk of asymptomatic neurosyphilis is unclear;

How to interpret CSF biologic variables in HIV-positive patients?

HIV infection may result in CSF pleocytosis and raised protein concentration.29, 44, 51 Therefore, the interpretation of mild modification of CSF cells count and protein concentration is difficult in patients coinfected with syphilis and HIV.29 Some authors have suggested that a CSF pleocytosis exceeding 20 cells/mm3 is more likely attributable to neurosyphilis than to the HIV infection.52

The diagnosis of neurosyphilis should chiefly rely on clinical signs and symptoms and CSF syphilis

Does HIV modify the serology titers at presentation of syphilis?

The polyclonal B-cell activation that occurs early in HIV infection may theoretically lead to false-positive tests.

In a 1993 study, the baseline RPR titers were higher among 31 HIV-infected patients (median, 128) than among 19 HIV-negative patients (median, 32), although the difference was significant only in the subgroup of those with first-episode syphilis (P = .05).35 In another study among HIV-infected patients, the RPR/VDRL titers tended to be lower in primary and higher in secondary

Does HIV infection modify syphilis treatment response?

The United Kingdom 2008 and the European 2001 guidelines recommend treating syphilis as appropriate for the stage of infection, regardless of the patient's HIV status.48, 49 The USA 2006 guidelines recommend treating syphilis in HIV-infected patients as in HIV-negative patients, although mentioning “some specialists recommend additional treatment” for primary and secondary syphilis—namely three intramuscular (IM) injections of benzathine penicillin G (2.4 million U) instead of one injection.11

Does the CD4 cell count modify syphilis treatment response in HIV-infected patients?

Several studies suggest that CD4 count does not correlate with serologic failure.28, 38 A retrospective study evaluated the syphilis serologic response to treatment among 56 HIV-infected patients.66 During a mean follow-up of 2 years, a relapse occurred in 10 patients (17.9%) and was associated with positive baseline CSF-VDRL in 4 of 7 (57%) and rash during secondary syphilis in 4 of 14 (29%), although the relapse rate was not associated with the CD4 cell count.66

Conversely, syphilis serologic

Conclusions

Few large-scale properly designed controlled studies have compared the syphilis baseline presentation and treatment response according to HIV status. There are significant discrepancies among experts. Some experts recommend more conservative management in HIV-infected patients, for instance, treating more heavily the syphilis infection and performing more widely a lumbar puncture; and some consider that in most patients syphilis should be managed similarly regardless of the patient's HIV status.

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