Signs and Symptoms of Initial HIV Infection
Acute HIV infection presents with an influenza-like or mononucleosis-like illness in 50-80% of cases, characterized by fever, malaise, lymphadenopathy, and rash, typically occurring within 2-4 weeks after exposure and before antibody seroconversion. 1
Cardinal Clinical Features
The most common presenting signs and symptoms include:
- Fever - Nearly universal in symptomatic acute HIV infection 1, 2, 3
- Lymphadenopathy - Swollen or enlarged lymph nodes, often cervical 1, 2, 3
- Pharyngitis/sore throat - Frequently with exudative tonsillopharyngitis 1, 2, 3
- Rash - Maculopapular rash affecting trunk and extremities, may include palpable purpura 1, 2, 3
- Myalgias and arthralgias - Muscle and joint pains 1, 4
- Fatigue and malaise - Profound tiredness and feeling generally unwell 1, 4, 3
- Headache - Common neurological symptom 1, 3
Additional Clinical Manifestations
Beyond the cardinal features, patients may present with:
- Night sweats 1
- Oral ulcerations 1, 2
- Conjunctivitis 2
- Gastrointestinal symptoms - Nausea, vomiting, diarrhea 2, 3
- Weight loss 5
- Cough and respiratory symptoms 2, 3
- Neurological complications - Aseptic meningitis, peripheral neuropathy 1, 5, 3
Laboratory Abnormalities
Common laboratory findings during acute HIV infection include:
- Lymphopenia - Decreased lymphocyte count 2
- Thrombocytopenia - Decreased platelet count 2
- Elevated transaminases - Liver enzyme elevation 4
Critical Diagnostic Considerations in Patients with Recurrent EBV
In a patient with recurrent EBV infection presenting with these symptoms, distinguishing acute HIV from EBV reactivation or chronic active EBV (CAEBV) is essential. 6, 7
Key Distinguishing Features:
- Acute HIV typically presents with a more acute onset (days to 2 weeks) after exposure, whereas CAEBV requires persistent symptoms for >3 months 1, 7
- Both conditions can present with fever, lymphadenopathy, pharyngitis, and fatigue, making clinical distinction challenging 1, 2
- EBV-associated illness more commonly presents with splenomegaly and atypical lymphocytosis, while acute HIV more frequently causes diffuse rash and oral ulcers 1, 2
Timing and Natural History
- Symptom onset occurs within 2-6 weeks after HIV exposure in most symptomatic cases 1
- Duration of acute retroviral syndrome typically lasts 1-2 weeks, with symptoms resolving spontaneously 2
- Prevalence of symptoms: approximately 50-80% of newly infected individuals experience symptomatic acute HIV infection 5, 8
- In community-based screening, 52% of patients with acute HIV reported ongoing symptoms at testing, with another 28% reporting symptoms within the preceding 14 days 8
Diagnostic Approach
HIV RNA viral load testing is essential for diagnosis during acute infection because antibody tests are typically negative or indeterminate during this window period. 1, 4
Testing Algorithm:
- Initial antibody testing will be negative or indeterminate during acute infection 1, 3
- HIV RNA PCR or p24 antigen testing is required for diagnosis when acute infection is suspected 1, 4, 3
- Repeat antibody testing at 4-6 weeks and 12 weeks post-exposure to document seroconversion 1
Clinical Pitfalls to Avoid
- Do not dismiss viral syndrome symptoms in patients with HIV risk factors, even if initial antibody testing is negative 1, 4
- Maintain high index of suspicion in patients presenting with mononucleosis-like illness who test negative for EBV, CMV, and other common causes 2, 3
- Consider acute HIV in any patient with unexplained fever, lymphadenopathy, or rash combined with recent high-risk exposure 3
- In patients with known recurrent EBV, persistent fever beyond 10 days warrants evaluation for both CAEBV/HLH and consideration of acute HIV if new exposure occurred 6
Importance of Early Recognition
Recognition of acute HIV infection is critical because it provides an opportunity for immediate antiretroviral therapy initiation, which may improve long-term prognosis and prevent transmission to others. 1, 4