Clinical outcomes of syphilis in HIV-negative and HIV-positive MSM: occurrence of repeat syphilis episodes and non-treponemal serology responses

Sex Transm Infect. 2022 Mar;98(2):95-100. doi: 10.1136/sextrans-2020-054887. Epub 2021 Feb 19.


Objectives: HIV-positive men who have sex with men (MSM) may be at a higher risk of repeat syphilis, have different clinical manifestations and have a different serological response to treatment compared with HIV-negative MSM. The objective of this study was to assess whether HIV-negative and HIV-positive MSM with infectious syphilis (primary, secondary or early latent) differed in history of previous syphilis episodes, disease stage and non-treponemal titre of initial and repeat episodes, and the titre response 6 and 12 months after treatment. Furthermore, determinants associated with an inadequate titre response after treatment were explored.

Methods: This retrospective analysis used data of five longitudinal studies (four cohorts; one randomised controlled trial) conducted at the STI clinic in Amsterdam, the Netherlands. Participants were tested for syphilis and completed questionnaires on sexual risk behaviour every 3-6 months. We included data of participants with ≥1 syphilis diagnosis in 2014-2019. Pearson's χ² test was used to compare HIV-negative and HIV-positive MSM in occurrence of previous syphilis episodes, disease stage of initial and repeat syphilis episode and non-treponemal titre treatment responses.

Results: We included 355 participants with total 459 syphilis episodes. HIV-positive MSM were more likely to have a history of previous syphilis episodes compared with HIV-negative MSM (68/90 (75.6%) vs 96/265 (36.2%); p<0.001). Moreover, HIV-positive MSM with repeat syphilis were less often diagnosed with primary syphilis (7/73 (9.6%) vs 36/126 (28.6%)) and more often diagnosed with secondary syphilis (16/73 (21.9%) vs 17/126 (13.5%)) and early latent syphilis (50/73 (68.5%) vs 73/126 (57.9%)) (p=0.005). While not significantly different at 12 months, HIV-negative MSM were more likely to have an adequate titre response after 6 months compared with HIV-positive MSM (138/143 (96.5%) vs 66/74 (89.2%); p=0.032).

Conclusions: In repeat syphilis, HIV infection is associated with advanced syphilis stages and with higher non-treponemal titres. HIV infection affects the serological outcome after treatment, as an adequate titre response was observed earlier in HIV-negative MSM.

Keywords: HIV; serology; syphilis.

MeSH terms

  • Adult
  • Antibodies, Bacterial / blood
  • Antibodies, Bacterial / immunology
  • Data Analysis
  • HIV Infections / complications
  • HIV Infections / epidemiology*
  • Homosexuality, Male / statistics & numerical data*
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Retrospective Studies
  • Risk-Taking
  • Serologic Tests / statistics & numerical data
  • Sexual Behavior
  • Syphilis / epidemiology*
  • Syphilis / immunology*
  • Treponema / immunology*


  • Antibodies, Bacterial

Supplementary concepts

  • Syphilis, secondary