What laboratory test should be ordered for a male patient with high-risk sexual behavior, including multiple male partners, and no symptoms of herpes simplex virus (HSV) infection?

HSV-2 Serologic Screening for Asymptomatic MSM with High-Risk Sexual Behavior

For an asymptomatic male patient with multiple male partners and high-risk sexual behavior, order type-specific HSV-2 serology (glycoprotein G-based assay) as part of comprehensive STI screening, recognizing this represents a selective screening approach rather than universal screening. 1

Rationale for Selective HSV-2 Screening in This Population

The 2014 International Antiviral Society-USA guidelines explicitly recommend considering routine screening for HSV-2 infection in high-risk populations, including men who have sex with men (MSM) with multiple partners. 1 This recommendation acknowledges that:

• Multiple sexual partners represent a well-established risk factor for HSV-2 acquisition, with seroepidemiologic studies consistently demonstrating higher HSV-2 prevalence among individuals with increased partner numbers. 2, 3

• MSM attending STD clinics have substantially higher rates of HSV-2 infection compared to general populations, making targeted screening more cost-effective in this demographic. 2

• Approximately 20% of HSV-2 seropositive persons remain asymptomatic, meaning they are unaware of their infection status and cannot take measures to prevent transmission. 1

Specific Test to Order

Order: Type-specific HSV-2 antibody test (glycoprotein G-based serology) 1, 4

The test must be:

• Glycoprotein G-based (gG-2 specific), as conventional serologic techniques cannot discriminate between HSV-1 and HSV-2 antibodies. 2, 5
• Type-specific for HSV-2, since HSV-1 antibodies are highly prevalent in the general population and do not indicate genital herpes risk. 4, 6

Important Caveats About HSV-2 Serologic Testing

Test Performance Limitations

Be aware that commercially available HSV-2 serologic assays have significant false-positive rates, particularly in low-prevalence populations. 1 The 2021 CDC guidelines note:

• Index values ≥3.0 may be sufficient for diagnosis without confirmatory testing, though false positives have been documented even at index values >3.5. 1
• Consider confirmatory testing with Biokit HSV-2 Rapid Test or Western blot if the initial result is positive with an index value <3.0, though access to these tests may be limited. 1

Contrast with USPSTF Recommendations

The U.S. Preventive Services Task Force (USPSTF) recommends AGAINST screening for HSV-2 in asymptomatic adolescents and adults (Grade D recommendation). 1, 7 However, this recommendation applies to the general population with low pretest probability of infection. 1

The key distinction is that your patient has high pretest probability based on:

• Multiple sexual partners 1
• MSM status in the context of high-risk sexual behavior 1
• Potential exposure to partners with unknown HSV-2 status 1

Clinical Management Based on Results

If HSV-2 Serology is Positive

Offer suppressive antiviral therapy (valacyclovir, acyclovir, or famciclovir) to:

• Reduce asymptomatic viral shedding and transmission risk to partners 1
• Prevent future symptomatic outbreaks 1

Counsel the patient that:

• Suppressive therapy reduces but does not eliminate transmission risk 8
• Condom use should be encouraged during all sexual exposures 7
• Partners should be informed of HSV-2 status 8
• Type-specific serologic testing of partners can determine their infection status 8

If HSV-2 Serology is Negative

Provide risk-reduction counseling including:

• Condom use to reduce HSV-2 acquisition risk 1
• Recognition of genital symptoms that warrant immediate evaluation 1
• Consider repeat screening at 3-6 month intervals given ongoing high-risk behavior 1

Comprehensive STI Screening Panel for This Patient

Do not screen for HSV-2 in isolation. The 2014 IAS-USA guidelines recommend routine periodic screening for common STIs in MSM at 3-6 month intervals based on risk factors. 1 Your complete screening panel should include:

• Syphilis: RPR or VDRL plus treponemal-specific test (EIA or CIA) 1
• HIV: Fourth-generation antigen/antibody test 1
• Gonorrhea and Chlamydia NAAT from:
  • Urine 1
  • Rectal swab (if receptive anal sex) 1
  • Pharyngeal swab (if receptive oral sex) 1
• Hepatitis B and C screening (if not previously vaccinated/infected) 1
• HSV-2 type-specific serology 1

Common Pitfalls to Avoid

• Do not order HSV-1 serology or non-type-specific HSV antibody tests, as these do not provide clinically useful information for genital herpes risk assessment. 4, 6

• Do not use HSV PCR or viral culture in the absence of active lesions, as these tests require active mucocutaneous lesions for diagnosis. 9, 7

• Do not order IgM antibody testing, as IgM responses occur in approximately one-third of recurrent HSV-2 cases and cannot distinguish acute from recurrent infection. 9

• Do not assume a negative HSV-2 serology definitively excludes recent infection, as seroconversion typically takes 2-12 weeks after exposure. 3