What is the rationale for testing asymptomatic men who have sex with men (MSM) for Immunoglobulin G (IgG) serum antibodies against Herpes Simplex Virus (HSV)?

HSV-2 IgG Serologic Testing in Asymptomatic MSM

Type-specific HSV-2 serologic testing using glycoprotein G-based assays should be offered to asymptomatic men who have sex with men (MSM) because they represent a high-risk population where identifying undiagnosed infection can enable counseling about transmission prevention, suppressive therapy options, and partner notification. 1

Rationale for Testing MSM as a High-Risk Population

MSM are explicitly identified as a target population for HSV-2 serologic screening by multiple guideline organizations, distinguishing them from the general population where routine screening is not recommended. 1 This recommendation is based on:

• Epidemiologic risk factors: MSM have higher rates of HSV-2 infection compared to the general population, similar to their elevated risk for other sexually transmitted infections. 2
• High-risk sexual behaviors: The focus should be on identifying high-risk sexual behavior patterns rather than sexual orientation alone when determining screening appropriateness. 2
• Potential for transmission reduction: Identifying asymptomatic HSV-2 infection allows for counseling about asymptomatic viral shedding and offers the option of suppressive antiviral therapy to reduce transmission risk to partners. 2

Contrast with General Population Recommendations

The approach to MSM differs fundamentally from general population screening:

• The USPSTF explicitly recommends against routine serologic screening for HSV-2 in asymptomatic adolescents and adults in the general population (Grade D recommendation), concluding that harms outweigh benefits. 2, 3
• However, this recommendation does not apply to high-risk groups including MSM, where targeted screening is considered appropriate. 1
• The rationale for not screening the general population is that most infections are asymptomatic, treatment of asymptomatic infection doesn't improve long-term health outcomes in low-risk individuals, and false-positive results can cause psychological harm. 2

Testing Methodology and Interpretation

When screening asymptomatic MSM:

• Use type-specific serologic testing with glycoprotein G-based assays, which have approximately 97% sensitivity and 98% specificity for HSV-2 antibodies. 1
• Collect venous blood samples for serologic testing; nucleic acid amplification tests (NAATs) are inappropriate for screening asymptomatic individuals without lesions. 1
• For low positive results (index value <3.0), confirmation with a second test using a different glycoprotein G antigen is recommended, as false positives are more common in individuals with HSV-1 infection. 1
• A negative result within 12 weeks of potential exposure may represent the "window period" and should be repeated after 12 weeks if recent acquisition is suspected. 1

Clinical Management Following Positive Results

When HSV-2 serology is positive in an asymptomatic MSM patient:

• Counsel about the natural history of HSV-2 infection, including potential for recurrent episodes, asymptomatic viral shedding (which occurs in approximately 80-90% of cases), and sexual transmission risk. 1, 4
• Offer suppressive antiviral therapy as an option to reduce both recurrences and transmission risk to sexual partners, even though the patient is currently asymptomatic. 2
• Suppressive therapy can be considered for transmission prevention in MSM based on the mechanism of suppressing viral shedding, despite studies being conducted primarily in heterosexual couples. 2
• Approximately 20% of HSV-2 seropositive persons do not recognize genital symptoms consistent with genital herpes, making identification through screening particularly valuable. 2

Important Caveats and Pitfalls

• Do not perform HSV molecular assays (PCR/NAAT) in the absence of genital ulcers, as HSV shedding is intermittent and swabs obtained without lesions are insensitive and unreliable. 1, 4
• Avoid IgM testing for screening, as approximately one-third of patients with recurrent HSV-2 infection have IgM responses, making it unreliable for distinguishing acute from chronic infection. 1
• False-negative serologic results can occur in 12-30% of patients with established HSV infection, so clinical suspicion should guide repeat testing if indicated. 5
• Index values between 1.1-2.9 have only 39.8% specificity (60% false positive rate), while values ≥3.0 have 78.6% specificity (21% false positive rate), necessitating confirmatory testing for low positive results. 1