HIV infection doesn't generally affect the response to syphilis treatment

Well-controlled HIV infection does not have a significant impact on the serological response to treatment for syphilis, Swiss investigators report in the online edition of Clinical Infectious Diseases. However, they found that syphilis stage was a significant factor in the response to treatment.

“HIV coinfection did not influence the overall time to serological response to treatment,” write the authors. “The clinical stage of syphilis had a significant impact on the serological response; compared with the primary stage, latent syphilis showed a slower treatment response.”

The sexually transmitted infection syphilis is a global health problem. There are an estimated 12 million new cases each year, 90% of which are in developing countries. New diagnoses of syphilis are also increasing in industrialised countries, and a large number of infections involve people with HIV.

Syphilis can be treated with antibiotics. Serological monitoring is used to monitor the response to such treatment. 

Studies conducted in the early years of the HIV epidemic suggested that infection with HIV led to a poorer response to syphilis treatment. However, in the era of modern antiretroviral therapy, it is uncertain if this is still the case. It is also unclear if the syphilis stage has an impact on individual responses to therapy.

Given these uncertainties, investigators in Switzerland designed a retrospective study involving 264 people. Their aims were to compare serological response to treatment between different stages of syphilis and to examine the influence of HIV infection.

The people included in the study received care between 1999 and 2008 and received treatment within two weeks of their syphilis diagnosis. For most of them, therapy consisted of one or three doses of Benzathine penicillin G. Serological follow-up was performed 20 to 375 days after therapy.

Three different methods were used to monitor serological response:

• The Veneral Disease Research Laboratory (VDRL) test.
• An IgM capture ELISA.
• The Treponemal Pallidum Particle Agglutination (TPPA) test.

Most of the people in the study (92%) were men and 42% were known to be living with HIV. The majority of people with HIV received aggressive treatment and received three doses of penicillin G.

In all, 90 people presented with primary syphilis, 133 with secondary syphilis, 33 with latent infection and eight with tertiary syphilis.

Initial VDRL and TPPA syphilis titres were significantly lower (p < 0.001) and more likely to be negative (p < 0.001) for people with primary syphilis compared to other stages of the disease.

However, 7% of people with primary syphilis with negative VDRL and TPPA tests had positive serology using the ImG test.

“We therefore suggest,” write the authors, “that in cases of suspected early infection specific IgM ELISA should be used in addition to other screening tests. It is important that clinicians communicate suspicion of an early infection to the laboratory.”

The serological response to therapy was then monitored.

VDRL analysis showed that a response (fourfold drop in titre or reversion to non-reactive) was achieved within a median of 37 days for people with primary infection, 49 days for those with secondary syphilis and 68 days for people with latent syphilis.

Three months after treatment 85 to 100% of those with primary syphilis had achieved a treatment response, as had 76 to 89% of people with secondary syphilis and between 44 and 79% of people with latent infection.

VDRL serological response was affected by syphilis stage. Compared to primary syphilis, latent infection was associated with a significantly slower treatment response (HR = 0.34; 95% CI, 0.2-0.57) and there was a trend towards a slower response for people with secondary syphilis (HR = 0.74; 95% CI, 0.53-1.05).

Infection with HIV did not have a major impact on the response to treatment. However, people living with HIV who had primary syphilis and a CD4 cell count below 500 cells/mm³ had a slower response compared to HIV-negative people who also had primary syphilis (HR = 0.37; 95% CI, 0.17-0.81; p = 0.012).

“As most of our HIV infected patients probably had a restored immune system, we would not expect to find a significant difference in regard to serological response rate,” comment the investigators.

A total of 190 people were followed for a year or until their VDRL test ceased to be reactive. Some 81% had a non-reactive test within twelve months. People who continued to have a reactive test after this point were more likely to have latent or tertiary syphilis 52 vs 9% of reactors (p < 0.001). Almost all these patients had baseline high titres. For one person, it took 4.2 years for tests to cease to be reactive.

Using the ImG test, the median time to a treatment response was 130 days for people with primary syphilis, 245 days for those with secondary infection and 202 days for people with latent syphilis. Treatment response was not influenced by HIV infection, regardless of CD4 cell count. However, both secondary and latent syphilis were associated with a slower treatment response than primary syphilis.

“Our study provides evidence that a combination of the TPPA test and an IgM ELISA is superior to the VDRL for diagnosing of syphilis,” comment the authors. “The syphilis disease stage significantly influences treatment response, whereas HIV coinfection has an impact on the response only in primary syphilis.”

Knaute DF et al. Serological response to treatment of syphilis according to disease stage and HIV status. Clin Infect Dis: online edition, 2012.