Previous syphilis not linked to brain injury in Ontario HIV study

Before effective HIV treatment (ART) was available, people with HIV had weakened immune systems. As a result, they could develop injury to the brain or surrounding tissue and serious infections caused by several microbes. HIV itself could affect the brain and cause problems with memory and thinking clearly. In extreme cases, HIV-related brain-injury could lead to changes in personality.

Another issue that could result in brain injury was neurosyphilis. This occurs when the germs that cause syphilis (treponemes) spread to the brain.

Effective HIV treatment first became available in 1996. When taken as directed, ART helps to suppress levels of HIV in the blood and continued treatment keeps it suppressed. This suppression of HIV allows the immune system to begin to repair itself. The power of ART is so profound that researchers expect that many ART users will have near-normal life expectancy.

Syphilis and the brain

A team of researchers in Ontario wanted to investigate the impact of previous syphilis on assessments of memory, speed of thinking, learning, information processing and other higher cognitive functions in people with HIV in the current era. Tests that explore these cognitive functions are called neuropsychological testing.

The researchers analyzed data collected from 1,288 people with HIV who underwent neuropsychological assessments. The researchers also analyzed information in participants’ medical records, paying particular attention to data from 271 people who had diagnoses of syphilis.

The researchers found no relationship between a diagnosis of syphilis and any impact on neuropsychological testing. Note that past episodes of syphilis in participants were treated.

Although not the focus of the study, researchers found that nearly 40% of participants had depression. This condition can affect memory and clear thinking, so researchers took this into account when analyzing their results. Their finding of such a large proportion of people with depression also points to the importance of screening people with HIV for mental health issues and offering treatment when necessary.

The present study underscores the importance of initiating and taking ART, as well as the screening and treatment of syphilis.

About syphilis

Syphilis is a disease caused by the germ Treponema pallidum. Syphilis can be spread via sex and sharing equipment used for injecting drugs. Initial infection with T. pallidum can cause a painless sore or lesion in or on the genitals, anus, mouth or throat. This sore or lesion may be unnoticed particularly if it is inside the body. Shortly after infection, the germs that cause syphilis spread and can infect the eyes, brain, bones, heart and blood vessels, liver, kidneys and other vital organs. Syphilis can also affect the fetus during pregnancy. Syphilis can cause a wide array of symptoms that may initially be mild or mimic other conditions. The good news is that syphilis can be uncovered with a simple blood test and most people can be cured with a course of treatment. However, people can become reinfected with syphilis in the future (through the routes previously mentioned), so regular syphilis testing is important.

Study details

A brief average profile of the 1,288 participants when they entered the study is as follows:

  • age – 44 years
  • major ethno-racial groups: White – 54%; Black – 26%
  • depression diagnosed – 37%
  • taking ART – 81%
  • drug use – 18%; researchers defined drug use as taking any of the following in the past six months – methamphetamine, cocaine/crack, opioids, tranquilizers and “club drugs”
  • lowest-ever CD4+ count – 190 cells/mm3
  • current CD4+ count – 450 cells/mm3
  • time since first syphilis diagnosis – 3.4 years
  • number of episodes of syphilis: none – 83%; one – 14%; two or more – 3%

Data were collected between January 2008 and December 2017. Researchers focused their analysis on 271 people who were diagnosed with syphilis.

On average, participants were in the study for two years.


During the study there were 366 episodes of syphilis among 271 people.

Researchers found no impact of a history of syphilis on neuropsychological assessments.

Focus on neurosyphilis

During the study, 23 people were diagnosed with neurosyphilis.

Researchers noted that people who were diagnosed with neurosyphilis were more likely to have the following factors than people without neurosyphilis:

  • used drugs in the past six months – 60% vs. 27% (the researchers did not publish information about how drugs were administered)
  • a detectable viral load (more than 50 copies/mL) – 60% vs. 31%
  • a longer duration of HIV infection – 12 years vs. 5 years

Despite these differences, researchers did not find any impact of a history of neurosyphilis on neuropsychological testing.

Bear in mind

Historically, neurosyphilis appeared to be more common among some people with HIV in the time before ART was available. What’s more, neurosyphilis was associated with a range of brain complications among people with HIV in the pre-ART era. However, the present study did not find that syphilis had a significant impact on the functioning of the brain. The researchers advanced several possible reasons for this, as follows:

  • Depression had a greater impact on cognitive function than syphilis, and depression was common among study participants.
  • It is possible that people with problems with memory and thinking clearly caused by syphilis did not participate in the study.
  • Neuropsychological assessments for this study took about 30 minutes to complete. More extensive assessments lasting two hours could have been done. Such assessments could have found subtle changes caused by syphilis (or other factors). However, it may be difficult to recruit and retain people for a study if more time consuming and complex assessments were used.
  • During the study period more effective HIV treatments (a group of drugs called integrase inhibitors) were introduced and regimens were simplified. Such changes may have led to better control of HIV (via easier adherence) and a stronger immune system.
  • More people could have initiated ART earlier in the course of HIV infection, and this could have preserved their neurocognitive functions. The researchers stated that people in the study “had generally good neurocognitive functioning overall (though less than population norms).”
  • The researchers stated that any impact of syphilis on brain health “may be dwarfed by the benefit of modern ART.”
  • People in the study were relatively young; results may be different in older people.
  • Due to frequent screening, syphilis in the study population may have been quickly uncovered by doctors and nurses and promptly treated. These factors may have minimized any neurological injury caused by syphilis.

Depression and sexually transmitted infections (STIs)

As mentioned earlier, a large proportion of people in the study had depression. The researchers noted that previous research has found a link between depression and newly diagnosed STIs. They stated that their finding (about high rates of depression) underscores the importance of screening study participants for mental health conditions when conducting studies of neurocognitive function in the future.

—Sean R. Hosein


Christensen BL, Tavangar F, Kroch AE, et al. Previous syphilis not associated with neurocognitive outcomes in people living with human immunodeficiency virus in Ontario, Canada. Sexually Transmitted Diseases. 2023 Jan 1;50(1):34-41.