What should be done for a patient presenting with symptoms of acute HIV infection, such as fever, rash, sore throat, or muscle aches, following a potential exposure?

Management of Acute HIV Infection

For patients presenting with symptoms suggestive of acute HIV infection following potential exposure, immediately perform HIV RNA testing alongside antibody/antigen testing, and refer urgently to an HIV specialist for same-day initiation of antiretroviral therapy if RNA is positive. 1

Diagnostic Approach

Maintain High Clinical Suspicion

• Clinicians must maintain a high level of suspicion for acute HIV infection in any patient with compatible symptoms (fever, rash, sore throat, muscle aches resembling influenza or mononucleosis) who reports recent high-risk behavior. 1
• An estimated 40-90% of persons acquiring HIV will experience these acute symptoms, making clinical recognition essential. 1

Immediate Testing Strategy

• Use dual testing immediately: Perform both a fourth-generation HIV antibody/p24 antigen immunoassay AND HIV RNA testing (PCR or bDNA) when acute infection is suspected. 1
• The fourth-generation combination test has sensitivity and specificity greater than 99.5% and can detect infection earlier than antibody-only tests. 2, 3
• HIV RNA testing is critical because antibody tests may still be negative or indeterminate during acute infection when viremia is present but seroconversion is incomplete. 4, 1
• Fourth-generation testing identifies approximately 23% of new HIV diagnoses as acute infections that would be missed by older technology. 2

Interpretation of Results

• Laboratory evidence of acute HIV infection includes detectable HIV RNA in plasma together with a negative or indeterminate HIV antibody test. 4, 1
• An indeterminate antibody test indicates the person is in the process of seroconversion. 4, 1
• Do not rely on p24 antigen testing alone, as a negative result does not rule out acute infection. 4

Immediate Management

Urgent Referral and Treatment Initiation

• If HIV RNA testing is positive, refer the patient immediately to an HIV specialist for consideration of antiretroviral therapy on the same day. 1
• Many experts recommend antiretroviral therapy for all patients who demonstrate laboratory evidence of acute HIV infection. 4, 1
• If clinical suspicion is high, withhold PrEP pending test results and consider administration of a fully suppressive ART regimen (early treatment). 1

Rationale for Immediate Treatment

Early antiretroviral intervention during acute infection serves four critical purposes: 4

• Suppresses the initial burst of viral replication and decreases virus dissemination throughout the body
• Decreases the severity of acute disease symptoms
• Potentially alters the initial viral "set-point," which may affect the rate of disease progression
• Reduces the rate of viral mutation by suppressing viral replication

Treatment Window Considerations

• Treatment is most beneficial when initiated during documented acute infection (positive RNA with negative/indeterminate antibody). 4
• Experts also consider therapy for patients in whom seroconversion has been documented within the previous 6 months, as virus replication in lymphoid tissue may not be maximally contained during this period. 4

Post-Exposure Prophylaxis Considerations

If Exposure Was Recent (Within 72 Hours)

• Consider and initiate post-exposure prophylaxis (PEP) as soon as possible if the exposure occurred within 72 hours. 5
• PEP is a 28-day course of antiretroviral medications. 5
• Perform rapid HIV testing or laboratory-based antigen/antibody combination test as soon as possible after potential exposure. 5

Follow-Up Testing Schedule

• Baseline testing at time of exposure 5
• Interim testing at 4-6 weeks using both HIV antigen/antibody test and HIV nucleic acid test (NAT) 5
• Final testing at 12 weeks after exposure using laboratory-based HIV antigen/antibody combination immunoassay and diagnostic HIV nucleic acid test 5
• The 4-6 week testing may be deferred for individuals who started PEP within 24 hours and did not miss any doses. 5

Additional Testing and Screening

Comprehensive Baseline Assessment

• Test for other sexually transmitted infections, hepatitis B and C, and pregnancy (if applicable) at the time of HIV testing. 5
• For patients with fatty liver disease or elevated liver enzymes, baseline and ongoing liver function monitoring is required. 6
• Quarterly monitoring of renal function is standard for all patients being considered for PrEP. 6

High-Risk Population Screening

• Screen every 3 months for men who have sex with men, transgender persons, people who inject drugs, and those newly diagnosed with other STIs, as long as risk continues. 1
• At minimum, provide annual screening for persons at very high risk. 1

Critical Pitfalls to Avoid

• Never rely on antibody testing alone when acute HIV infection is suspected—the window period can miss highly infectious patients. 1, 2
• Do not delay treatment while waiting for confirmatory testing if clinical suspicion is high and RNA is positive—transmission risk is greatest during acute infection when viral loads are extremely high. 1
• Do not dismiss symptoms that resemble common viral illnesses in patients with recent high-risk behavior—acute HIV mimics influenza and mononucleosis. 1
• Never initiate PrEP without first ruling out acute HIV infection, as incomplete suppression could lead to resistance. 1