Eric S. Daar, MD

In This Article


The natural history of HIV infection usually begins within weeks of a sexual or percutaneous exposure to the genital secretions or blood of an infected individual. The diagnosis of primary or acute HIV infection allows for counseling to prevent subsequent transmission to others and enrollment into immunopathogenesis studies. In addition, recent investigation suggests that the initiation of antiretroviral therapy during this stage of disease may have a profound influence on long-term virologic control.

Primary HIV infection has been characterized as an acute "mononucleosis- or influenza-like" illness that manifests in up to 70% of newly infected individuals, usually occurring within 2-6 weeks of infection.[1,2] The syndrome varies from mild fever and myalgia to a severe illness such as meningitis and encephalitis.[2,3,4,5] In addition, laboratory abnormalities can include leukopenia, thrombocytopenia, and transaminase elevation.[5,6] Recent studies suggest that no single symptom or constellation of symptoms has sufficient sensitivity or specificity to allow for targeted screening for this clinical entity.[7,8,9] Consequently, any sexually active or needle-sharing individual with an acute illness suggestive of acute HIV should be offered screening for primary HIV infection. Since these persons may be in the seronegative window of infection, testing should include a virologic test in addition to assays for HIV antibodies. The optimal virologic test for diagnosing primary infection has not been defined. Testing for p24 antigen has shown > 99% specificity with a sensitivity of 75% to 90% in antibody-negative subjects, while quantitative assays for plasma HIV RNA are likely to have > 99% sensitivity, but occasionally result in false-positives. Of note, false-positive tests usually report HIV-1 RNA levels of < 10,000 copies/mL, in contrast to the > 100,000 copies/mL typically seen in those with primary HIV infection.[7,8,9]

Although the focus of this review is on the role of treatment during primary infection, the most compelling reason to make the diagnosis of primary infection is to provide counseling and early entry into care for newly infected individuals. The importance of risk-reduction counseling of newly diagnosed persons is emphasized by epidemiologic studies suggesting that a substantial amount of HIV transmission occurs from those with early infection.[10,11,12]


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