Blood Tests for STI Screening (Excluding HSV 1 and 2)
For comprehensive STI screening excluding herpes, you should order: HIV antibody testing, syphilis serology (RPR or VDRL with confirmatory treponemal test if positive), and hepatitis B surface antigen (HBsAg). These are the primary blood-based tests that screen for the most clinically significant sexually transmitted infections with serious morbidity and mortality implications 1, 2.
Core Blood Tests
HIV Testing
- Screen all patients aged 15-65 years regardless of risk factors 2
- For patients outside this age range, screen if increased risk factors present
- This is a Grade A recommendation with the strongest evidence base
Syphilis Serology
- Use nontreponemal tests (RPR or VDRL) as initial screening 3
- If positive, confirm with treponemal-specific tests (FTA-ABS, TPPA, or EIA/CIA)
- Screen all sexually active individuals at increased risk 1, 2
- Note: Some laboratories now use "reverse algorithm" starting with treponemal EIA/CIA, then confirming with RPR 4
Hepatitis B Surface Antigen (HBsAg)
- Screen persons at increased risk including those with multiple sexual partners, history of other STIs, or injection drug use 3, 2
- Particularly important for pregnant women (universal screening recommended) 3
Risk-Stratified Approach
High-risk sexual behaviors warranting all three blood tests include:
- Multiple current or recent sexual partners
- New sexual partner
- Inconsistent condom use
- Sex while under influence of alcohol/drugs
- Sex work involvement
- History of prior STIs 1
Important Caveats
What Blood Tests DON'T Screen For
Blood tests alone miss several important STIs that require swab-based testing:
- Chlamydia and gonorrhea require nucleic acid amplification tests (NAAT) from urine, vaginal, cervical, rectal, or pharyngeal specimens 4, 5
- These are the most common bacterial STIs and cannot be detected by blood work 1, 2
Timing Considerations
- Syphilis and HIV antibodies require time to develop after exposure
- For post-exposure screening, repeat testing at 12 weeks after potential exposure to allow for seroconversion 6
- Initial negative results don't exclude recent infection during the "window period"
Hepatitis C
While not traditionally classified as primarily sexually transmitted, hepatitis C antibody testing should be considered for:
- Men who have sex with men with high-risk practices
- Persons with HIV infection
- Those with injection drug use history 7
Screening Intervals
For ongoing risk: Annual screening is reasonable, though optimal intervals aren't firmly established 2. Rescreen when sexual history reveals new or persistent risk factors rather than adhering to rigid time intervals.
Common Pitfalls to Avoid
- Don't rely solely on blood work - You'll miss chlamydia and gonorrhea, which are far more prevalent than syphilis in most populations
- Don't order HSV serology for screening - The USPSTF recommends against screening asymptomatic individuals for herpes 2, and you've specifically excluded this
- Don't forget hepatitis B vaccination status - If not immune, vaccinate rather than just screen
- Don't use outdated syphilis tests - Ensure your laboratory uses current methodology; some still use older complement fixation tests with poor sensitivity 4
The evidence strongly supports this focused blood-based approach for the infections with the most serious consequences (HIV, syphilis, hepatitis B), while recognizing that comprehensive STI screening requires additional specimen collection methods 1, 2.