Asymptomatic neurosyphilis may need early intervention in people living with HIV

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Asymptomatic neurosyphilis may need early intervention in people living with HIV

Syphilis and HIV are two sexually transmitted infections (STIs) that often share the same path—and for people living with HIV (PLWH), this overlap can hide a silent danger: asymptomatic neurosyphilis. Caused by the bacterium Treponema pallidum, syphilis has plagued humanity for centuries, but its interaction with HIV creates unique risks—including a form of neurosyphilis that shows no symptoms yet can damage the brain and nervous system over time. A 2020 viewpoint in the Chinese Medical Journal, written by Hong-Jie Chen, Tao Yu, and Jie Peng from the State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, and Department of Infectious Diseases at Nanfang Hospital, Southern Medical University in Guangzhou, China, argues that this “silent” infection needs earlier intervention to prevent devastating long-term consequences.

Syphilis, HIV, and the Hidden Threat of Asymptomatic Neurosyphilis

Syphilis and HIV spread through similar routes—unprotected sex, shared needles—so PLWH are far more likely to be coinfected. What’s less known is that HIV weakens the immune system, making PLWH more susceptible to neurosyphilis—the stage where T. pallidum invades the central nervous system (CNS). Most people associate neurosyphilis with obvious symptoms: meningitis (brain inflammation), strokes, vision loss, or confusion. But asymptomatic neurosyphilis? It leaves no trace—no headaches, no numbness, no memory lapses. The only way to diagnose it is through a lumbar puncture (LP), a procedure that draws cerebrospinal fluid (CSF) from the lower spine to check for three key signs: too many immune cells (mononuclear pleocytosis), high protein levels, or a positive venereal disease research laboratory (VDRL) test—a marker for syphilis in the CNS.

Why Asymptomatic Neurosyphilis Matters

Here’s the critical truth: asymptomatic doesn’t mean harmless. Over months or years, the hidden infection can progress to late-stage neurosyphilis, leading to irreversible damage. One study found that 42% of patients with late neurosyphilis had brain infarctions (small strokes), 47% had mild to severe brain atrophy (shrinkage), and 16% had white matter demyelination (loss of the brain’s “insulation”). Even with treatment, these changes can persist—robbing people of their independence and quality of life.

The High Risk for PLWH

For PLWH, the odds of silent neurosyphilis are startling. A 2009 study of 46 PLWH with early syphilis found that 22% had asymptomatic neurosyphilis—no symptoms, but clear CSF abnormalities. Another study of 117 PLWH with CSF signs of neurosyphilis found that 33% had no neurological issues at all. These numbers aren’t small—and they challenge the current standard of care.

Guidelines vs. Reality: Who Needs a Lumbar Puncture?

Right now, the U.S. Centers for Disease Control and Prevention (CDC) only recommends LP for PLWH with neurological symptoms. But for PLWH, that’s not enough. Researchers have identified two key risk factors for asymptomatic neurosyphilis:

  1. A CD4+ T cell count below 350 cells/mL (CD4 cells are the immune system’s “soldiers” against HIV).
  2. A VDRL titer of 1:32 or higher (a measure of how active the syphilis infection is).

The European guidelines go further: they recommend CSF testing for all PLWH with these two risk factors. Repeat syphilis infections—common in PLWH—are also more likely to be asymptomatic, so even if someone’s had syphilis before, an LP might be needed.

The Challenge of Treatment: Penicillin and Beyond

Benzathine penicillin G (BPG) has been the gold standard for syphilis treatment for decades—and no penicillin-resistant strains of T. pallidum have been found. But BPG has a big flaw: it doesn’t penetrate the CNS well. For PLWH at high risk of asymptomatic neurosyphilis, this is a problem.

Some experts recommend longer courses of penicillin or drugs that cross the blood-brain barrier better, like ceftriaxone. A UK study of 130 PLWH used a 17-day regimen of procaine penicillin (a longer-acting form) plus probenecid (a drug that boosts penicillin levels) and saw a 98% success rate—far higher than standard BPG. But not all research supports longer BPG courses: a 2017 randomized trial found no difference in outcomes between one dose of BPG and three doses in PLWH with early syphilis.

Follow-Up Is Non-Negotiable

No matter the treatment, PLWH need careful follow-up. Regular blood tests to track VDRL titers (a drop in titer means the treatment is working) are essential. They also need to watch for the Jarisch-Herxheimer reaction—a flu-like response to penicillin that’s more common in HIV patients. Symptoms include fever, chills, and muscle aches, and they usually hit within 24 hours of treatment. While not life-threatening, it’s a sign the body is fighting the infection—and doctors need to monitor it closely.

The Bottom Line

Asymptomatic neurosyphilis is a hidden threat for PLWH—and current guidelines might be missing too many cases. To protect people, we need to expand LP criteria: if a PLWH has a CD4 count below 350 or a high VDRL titer, an LP should be on the table. For those who can’t or won’t get an LP, doctors should consider treatments that reach the CNS—even if it means stepping outside the standard guidelines. Silent infections don’t stay silent forever—and early intervention could mean the difference between a healthy life and a disabled one.

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