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  • People who take HIV PrEP usually have appointments at their health clinic every three months
  • At the clinic, lab tests, including ones for sexually transmitted infections, are typically done
  • A recent study suggests some PrEP users may need more frequent syphilis screening

When used as directed, HIV pre-exposure prophylaxis (PrEP) is very effective at reducing the risk of HIV infection. As part of the routine care of PrEP patients, visits to the clinic every three months are usually required. At these visits, assessments are done, including blood, urine and swabs for sexually transmitted infections (STIs). As well, prescriptions are renewed and discussions with a nurse or physician take place.


Over the past two decades, rates of one STI in particular—syphilis—have been increasing in Canada and other high-income countries. Syphilis is a multistage condition (with primary, secondary and tertiary stages) that can damage nerves, which results in loss of hearing and vision, as well as major organs such as the brain, heart, liver and kidneys. Syphilis can injure the fetus during pregnancy and cause complications in infants born to infected mothers. This STI can be detected with regular screening and can be treated with antibiotics.

Syphilis in PrEP users

Researchers in Melbourne, Australia, reviewed the medical records of men who have sex with men (MSM) who attended a local sexual health centre for PrEP. The centre had a PrEP clinic where patients were seen by appointment only. The centre also had an STI clinic where no appointment was necessary. Over a period of three years, the researchers compared syphilis diagnoses made among men who visited the PrEP clinic every three months for their scheduled appointments and men who were taking PrEP who visited the STI clinic in between their scheduled PrEP clinic appointments.

According to the researchers, “a substantial portion of primary (58%) and secondary (44%) syphilis diagnoses were made at interim STI clinic attendances, between PrEP appointments.” They added that “syphilis screening at routine three-monthly PrEP visits alone fails to detect a portion of primary and secondary syphilis infections and may be insufficient in preventing onward transmission.”

Study details

The Melbourne Sexual Health Centre has an appointment-only PrEP clinic and a separate walk-in clinic for STI assessment and treatment. Researchers retrieved medical information collected at the Sexual Health Centre between February 2016 and March 2019.

As previously mentioned, PrEP users made appointments for their three-monthly visits to the PrEP clinic. At those appointments they consulted a doctor and underwent routine STI screening. People with no symptoms of STIs did not undergo routine physical examination and generally self-collected specimens for STI screening.

The researchers noted that “PrEP users who developed STI symptoms could also attend the walk-in STI clinic outside their booked PrEP visits for additional STI testing and treatment.”


During the study period, 572 MSM attended the PrEP clinic. The rate of syphilis screening among men attending the PrEP clinic was high—96%. It was even higher among men who attended the STI clinic between scheduled PrEP appointments—99%.

During the study, there were 69 cases of syphilis in 61 men—eight of the men developed syphilis a second time.

The stages of syphilis diagnosed were as follows:

  • primary syphilis – 24 men
  • secondary syphilis – 16 men
  • early latent syphilis – 29 men

Primary syphilis

According to the researchers, among the 24 men diagnosed with primary syphilis, nearly 60% of cases “were diagnosed in the walk-in STI clinic rather than at a booked PrEP clinic visit.” All cases of primary syphilis diagnosed at the walk-in STI clinic were associated with symptoms.

The remaining cases of primary syphilis cases were diagnosed at the PrEP clinic during the routine three-monthly appointments. A majority of these men (60%) had symptoms.

Regardless of the clinic where syphilis was diagnosed (the PrEP clinic or walk-in STI clinic), the part of the body most commonly affected by primary syphilis was the penis (80%) and the remainder of the lesions affected the anus.

Secondary syphilis

There was a total of 16 men with secondary syphilis—44% were diagnosed at the walk-in STI clinic and 56% were diagnosed at the PrEP clinic. All the men who were diagnosed at the STI clinic had symptoms of secondary syphilis. Usually the symptoms involved rash and/or genital or oral lesions. In contrast, only one of the men whose case of secondary syphilis was diagnosed at the PrEP clinic disclosed symptoms at his clinic visit.

Early latent syphilis

There were 29 men diagnosed with early latent syphilis. A majority (76%) of these cases were diagnosed at the PrEP clinic through routine lab tests. The remaining cases were diagnosed through lab tests at the walk-in STI clinic. According to the researchers, visits to the STI clinic were likely driven by “possibly symptoms or screening for other STIs”.

Bear in mind

The present study had at least the following limitations:

  • It was relatively small.
  • Participants were attending one sexual health centre.
  • It is possible that some men could have been diagnosed with syphilis at other clinics in the city; this would have resulted in under-estimating the total number of syphilis cases.
  • The symptoms of primary and secondary syphilis could be different in other populations in other parts of the world.

Despite these limitations, the study underscores the importance of syphilis screening among PrEP users. Indeed, the researchers stated that their findings suggest that “three-monthly syphilis screening at routine PrEP visits alone is not adequate to detect significant numbers of primary and secondary syphilis cases among MSM taking PrEP before they are potentially infectious and transmissible.”

The researchers made several other important points:

To remedy the situation that they have uncovered, they recommended that “access to syphilis screening and testing between PrEP clinic appointments should be available so treatment of [newly diagnosed infections] can be administered without delay.”

“MSM who are commencing HIV PrEP should receive education and health promotion regarding the risk for syphilis and recognition of primary and secondary lesions; and the importance of disclosing potential symptoms at PrEP appointments to expedite treatment.”

MSM “should be advised of the need for regular syphilis testing, including at least three-monthly screening for [symptom-free] infection, and in addition, testing for any lesions or symptoms that develop between PrEP clinic appointments.”

—Sean R. Hosein


Infectious syphilis in Canada – Public Health Agency of Canada

Syphilis in Canada: Technical report on epidemiological trends, determinants and interventions – Public Health Agency of Canada

Canadian guidelines on sexually transmitted infections: Summary of recommendations for chlamydia trachomatis (CT), neisseria gonorrhoeae (NG) and syphilis – Public Health Agency of Canada

Syphilis – CATIE factsheet

High interest in syphilis pre- and post-exposure prophylaxis (PrEP and PEP) among men who have sex with men – CATIE News

Montreal doctors report on cases of syphilis affecting the eyes – CATIE News

British Columbia — increasing cases of syphilis affecting the eye  – CATIE News

Syphilis cases on the rise among HIV-positive people in Calgary – CATIE News


  1. Peel J, Chow EPF, Denham I, et al. Clinical presentation of incident syphilis among men who have sex with men taking HIV Pre-Exposure Prophylaxis in Melbourne, Australia. Clinical Infectious Diseases. 2021; in press.
  2. Leber A, MacPherson P, Lee BC. Epidemiology of infectious syphilis in Ottawa. Recurring themes revisited. Canadian Journal of Public Health. 2008 Sep-Oct;99(5):401-5
  3. O'Byrne P, MacPherson P. Syphilis. BMJ. 2019 Jun 28;365:l4159.