Investigating latent syphilis in HIV treatment-experienced Ethiopians and response to therapy

PLoS One. 2022 Jul 12;17(7):e0270878. doi: 10.1371/journal.pone.0270878. eCollection 2022.


Objectives: We investigated people with HIV (PWH) receiving combination antiretroviral therapy (cART) for latent syphilis infection prevalence, risk factors, treatment response, and neurosyphilis.

Methods: A prospective follow-up study was conducted on PWH and latent syphilis. The cases were randomly assigned to receive either benzathine penicillin G (BPG) or doxycycline (DOXY), and the posttreatment response was evaluated after 12 and 24 months. The traditional algorithm was used for serodiagnosis, and a semi-quantitative rapid plasma reagin (RPR) test monitored disease activity and treatment effectiveness.

Results: Of the 823 participants, 64.8% were women, and the mean age was 41.7±10 years. Thirty-one (3.8%) of the participants (22 males and nine females) had latent syphilis. The risk factors were male sex (aOR = 3.14), increasing age (aOR = 1.04 per year), and cART duration (aOR = 1.01 per month). Baseline RPR titers were: ≤1:4 in 19 (61.3%), between 1:8 and 1:32 in 10 (32.2%), and >1:32 in 2 (6.4%). None of the seven cerebrospinal fluid analyses supported a neurosyphilis diagnosis. In the 12th month of treatment, 27 (87.1%) had adequate serological responses, three (9.7%) had serological nonresponse, and one (3.2%) had treatment failure. Syphilis treatment was repeated in the last four cases with the alternative drug. In terms of adequate serologic response, both therapies were comparable at the 12th month, p = 0.37. All cases responded to treatment in the 24th month.

Conclusion: In PWH receiving cART, latent syphilis occurred more in men than women, suggesting an investigation of sexual practices and the impact of antenatal syphilis screening. Syphilis disease activity reduces in the latent stage. Therefore, the routine cerebrospinal fluid analysis contributes little to the diagnosis of asymptomatic neurosyphilis and the treatment success of latent syphilis. DOXY is an alternative to BPG, and cART improves serologic response to latent syphilis treatment.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Doxycycline / therapeutic use
  • Ethiopia
  • Female
  • Follow-Up Studies
  • HIV Infections* / complications
  • HIV Infections* / drug therapy
  • HIV Infections* / epidemiology
  • Humans
  • Male
  • Middle Aged
  • Neurosyphilis* / diagnosis
  • Neurosyphilis* / drug therapy
  • Neurosyphilis* / epidemiology
  • Penicillin G Benzathine / therapeutic use
  • Pregnancy
  • Prospective Studies
  • Syphilis* / diagnosis
  • Syphilis* / drug therapy
  • Syphilis* / epidemiology


  • Doxycycline
  • Penicillin G Benzathine