How should I order HIV fourth‑generation testing, VDRL (syphilis) screening, and tuberculosis work‑up (sputum smear/GeneXpert, chest X‑ray, and IGRA/TST) for a high‑risk patient?

Ordering HIV, VDRL, and TB Testing for High-Risk Patients

Order all three tests simultaneously at the initial visit: fourth-generation HIV antigen/antibody combination assay, syphilis screening (RPR or treponemal-specific antibody), and tuberculosis screening with IGRA (preferred) or TST, followed by chest X-ray if TB screening is positive. 1

HIV Testing Protocol

Initial Test Selection

• Order a fourth-generation HIV antigen/antibody combination assay as the screening test, which detects both HIV antibodies and p24 antigen, allowing detection of recent infection 2
• This is superior to older antibody-only tests because it identifies acute HIV infection when patients are most infectious but antibody tests may still be negative 1
• Use opt-out screening approach: inform the patient that HIV testing will be performed as routine care unless they decline, rather than asking permission 3

Confirmatory Testing Algorithm

• All reactive screening tests must be confirmed before diagnosis using HIV-1/HIV-2 antibody differentiation immunoassay 2
• If the differentiation assay is negative or indeterminate, order HIV RNA testing to detect acute infection 2
• Never diagnose HIV based on screening test alone 2

If HIV-Positive: Immediate Follow-Up Tests

• CD4 cell count and percentage to assess immune function and urgency of treatment 1
• Quantitative HIV RNA (viral load) to establish baseline 1
• HIV genotype resistance testing before starting therapy 1
• HLA-B*5701 testing if abacavir is being considered 1

Syphilis (VDRL) Testing Protocol

Initial Screening

• Order syphilis screening using your local protocol—either RPR (rapid plasma reagin) or treponemal-specific antibody tests 1
• Both approaches are acceptable; choice depends on your laboratory's standard protocol 1
• All patients should be screened for syphilis at initiation of care and periodically thereafter depending on risk 1

Critical Co-Infection Consideration

• HIV and syphilis co-infection is common and each infection may enhance transmission of the other through increased genital ulcers 4
• All HIV-positive patients should be regularly screened for syphilis 4
• Syphilis may present atypically in HIV-positive patients with higher rates of asymptomatic primary disease and more aggressive secondary disease 4

Dual Rapid Testing Option

• Dual HIV/syphilis rapid tests are available and show high performance (HIV sensitivity 99-100%, syphilis sensitivity 73-89%) 5, 6
• These can be particularly useful in high-risk settings to increase screening uptake 6

Tuberculosis Testing Protocol

Initial Screening Test

• Order IGRA (interferon-γ release assay) as the preferred test, especially if the patient has a history of BCG vaccination 1
• TST (tuberculin skin test) is an acceptable alternative if IGRA is not available 1
• All HIV-infected patients without prior tuberculosis history or positive screening should be tested at initiation of care 1

If TB Screening is Positive

• Order chest X-ray to rule out active tuberculosis before treating latent infection 1
• This is mandatory—never treat for latent TB without excluding active disease 1
• If active TB is excluded, treat for latent M. tuberculosis infection 1

Special Consideration for Advanced HIV

• Repeat TB testing in patients with advanced HIV disease (low CD4 counts) who initially had negative results but subsequently experience CD4 count increases 1
• Initial false-negative results can occur with severe immunosuppression 1

Timing and Frequency

Initial Visit

• Order all three tests simultaneously—there is no need to stagger them 1
• Results can be obtained within days for HIV and syphilis, and 24-72 hours for IGRA 1

Follow-Up Screening Intervals

• HIV: Annually for high-risk patients; every 3 months for very high-risk individuals (MSM, injection drug users, recent STI diagnosis) 2, 7
• Syphilis: Periodically based on ongoing risk; more frequently for high-risk patients 1
• TB: Repeat only if new exposure or if initial test was negative in setting of severe immunosuppression that later improves 1

Common Pitfalls to Avoid

• Never rely on risk-based screening alone—10-25% of HIV-positive individuals report no high-risk behaviors 2
• Never diagnose HIV without confirmatory testing—false positives occur and have devastating consequences 2
• Never treat latent TB without chest X-ray first—missing active TB leads to inadequate treatment and continued transmission 1
• Never assume negative syphilis serology rules out infection in HIV-positive patients—false-negative serology can occur in both primary and secondary syphilis 4
• Never use antibody-only HIV tests in high-risk patients with acute symptoms—fourth-generation tests are essential to detect acute infection 1, 2