I have positive HSV‑1 and HSV‑2 immunoglobulin G antibodies and a non‑reactive rapid plasma reagin test; what does this indicate and how should I manage it?

Interpretation of Your HSV Serology Results

Your results indicate established HSV-1 infection (index 3.05) but your HSV-2 result (index 2.12) has a high probability of being a false positive and should be confirmed with additional testing before accepting the diagnosis.

Understanding Your Specific Results

HSV-1 Result (Index 3.05)

• Your HSV-1 IgG index of 3.05 is well above the positive threshold and indicates true HSV-1 infection 1
• At index values ≥3.0, the test has 78.6% specificity, making this result reliable 1
• This represents past exposure to HSV-1, which could be oral or genital, and the antibodies persist indefinitely 2
• Approximately 70% of adults worldwide have HSV-1 antibodies, often acquired non-sexually in childhood 3

HSV-2 Result (Index 2.12) – Critical Concern

• Your HSV-2 index of 2.12 falls in the problematic range (1.1–2.9) where false-positive rates reach approximately 60%—meaning only 39.8% specificity 1, 3
• Individuals with HSV-1 infection (like you) are markedly more prone to false-positive HSV-2 results at low index values due to antibody cross-reactivity 1, 3
• Even at index values ≥3.0, specificity is only 78.6%, meaning more than 1 in 5 positive results may be false 1, 3

RPR (Non-Reactive)

• This rules out active syphilis infection, which is appropriate screening when evaluating sexually transmitted infections 1

Recommended Next Steps for HSV-2 Confirmation

Do not accept the HSV-2 diagnosis without confirmatory testing 1, 3

Immediate Actions:

1. Request confirmatory testing with a second assay using a different glycoprotein G antigen 1, 2

   • Using the Biokit HSV-2 rapid assay as confirmatory improves specificity from 93.2% to 98.7% 1, 3
   • This strategy increases positive predictive value from 80.5% to 95.6% 1

2. Consider Western blot/immunoblot testing (gold standard) if available 1

   • This is the most accurate serologic test but has limited availability 1, 2

3. Timing considerations for repeat testing 1, 3:

   • If possible exposure occurred within the past 12 weeks, wait until after the 12-week window to retest (antibodies may still be developing)
   • If exposure was more than 12 weeks ago, repeat testing in 4–6 weeks may help clarify the result

If Active Lesions Develop:

• PCR/NAAT testing of lesion swabs is the diagnostic gold standard with 96–98% sensitivity and 95–99% specificity 3, 4
• This would definitively establish whether you have HSV-2 genital infection 1
• Do not perform viral testing without active lesions—intermittent shedding makes swabs insensitive when lesions are absent 1, 4

Clinical Implications Based on Confirmed Results

If HSV-2 is Confirmed (After Additional Testing):

• HSV-2 is a chronic infection with higher rates of symptomatic recurrences and subclinical viral shedding compared to HSV-1 2
• Approximately 91% of HSV-2 seropositive persons remain unaware of their infection because symptoms are mild or unrecognized 4
• Most transmission occurs from persons who are asymptomatic or unaware of infection 4
• Treatment options include:
  • Episodic therapy for outbreaks
  • Suppressive therapy to reduce recurrences and transmission risk 2, 4

If HSV-2 is Not Confirmed:

• You have HSV-1 infection only, which is extremely common and often acquired non-sexually 3
• HSV-1 can cause genital herpes, though with less frequent recurrences than HSV-2 2

Critical Pitfalls to Avoid

• Do not diagnose HSV-2 infection based on this indeterminate serologic result alone—this can cause unnecessary psychological distress, relationship issues, and unwarranted treatment 3
• Do not rely on HSV-1 serology to determine genital vs. oral infection—HSV-1 antibodies cannot differentiate the site of infection 3
• Do not assume absence of symptoms means absence of infection—most HSV infections are asymptomatic or unrecognized 4
• Do not perform repeat serologic testing immediately after recent exposure—allow at least 12 weeks for adequate antibody development 1, 3