HIV (Primary HIV Infection) is the STI Most Commonly Associated with Flu-Like Symptoms
Primary HIV infection causes acute retroviral syndrome with flu-like symptoms in 65-95% of cases, making it the sexually transmitted infection most characteristically associated with this presentation. 1
Clinical Presentation of Acute HIV Infection
The acute retroviral syndrome typically presents with:
- Fever, malaise, lymphadenopathy, and skin rash occurring in the first few weeks after HIV infection, before antibody test results become positive 2
- Non-specific flu-like symptoms that are often mistaken for common viral illnesses 1
- Symptoms appearing during the window period when standard antibody tests may still be negative, requiring nucleic acid testing for diagnosis 2
Why This Matters Clinically
Symptomatic primary HIV infection is associated with faster clinical and immunological progression of HIV disease, making early recognition critical 1. The CDC explicitly recommends that HIV testing should be routinely offered when patients present with:
- Mononucleosis-like syndrome 2
- Unexplained lymphadenopathy 2
- Pyrexia of unknown origin 2
- Aseptic meningitis/encephalitis 2
Diagnostic Approach
When acute retroviral syndrome is suspected:
- Perform nucleic acid testing (HIV RNA or DNA PCR) immediately rather than waiting for antibody seroconversion, as standard antibody tests will be negative during this acute phase 2
- Positive screening antibody tests must be confirmed with Western blot or immunofluorescence assay before being considered diagnostic 2
- At least 95% of patients will have detectable HIV antibody within 6 months of infection 2
Treatment Implications
Initiation of antiretroviral therapy during primary HIV infection can delay onset of HIV-related complications and may influence long-term prognosis 2. Current recommendations include:
- Starting combination antiretroviral therapy with tenofovir and emtricitabine plus either darunavir/ritonavir or dolutegravir 1
- Early ART prevents HIV transmission and decreases viral and immunological reservoir constitution 1
Other STIs That Can Present with Systemic Symptoms
While HIV is the classic answer, other STIs can occasionally present with flu-like features:
- Secondary syphilis can present as a febrile illness with rash and constitutional symptoms 2
- Gonorrhea rarely presents with systemic symptoms 2
- Lymphogranuloma venereum (LGV) can cause systemic symptoms in addition to proctitis 2, 3
Critical Pitfall to Avoid
Do not rely solely on antibody testing when acute HIV infection is suspected clinically. The window period between infection and antibody seroconversion means standard HIV tests will miss acute infections 2. Always order HIV RNA/DNA testing when the clinical presentation suggests acute retroviral syndrome, even if the patient reports recent negative HIV testing 2.