Primary infection with human immunodeficiency virus (HIV) can occur with diverse clinical symptoms. Recognition of this syndrome in at-risk persons should prompt antibody testing and virologic assay, since patients with primary infection are just developing HIV antibodies. Diagnosing primary infection may decrease HIV transmission and enable consideration of early treatment. The optimal method for early diagnosis has not yet been determined. Daar and colleagues reviewed the sensitivity and specificity of virologic tests and presenting clinical symptoms in diagnosing primary HIV infection.

Three cohorts involving 436 patients potentially exposed to HIV infection and with compatible symptoms of primary infection were tested using slightly differing strategies. Primary infection was defined as a confirmed positive virologic test result with an HIV RNA level greater than 10,000 copies per mL with either a negative HIV antibody assay result or an indeterminate Western blot test result.

Combining fever, myalgia and rash increased the predictive value of symptoms, but no combination of symptoms identified more than 75 percent of patients with primary infection. HIV RNA assays were highly sensitive but associated with lower specificity and therefore yielded more false-positive results. The p24 antigen assay had a sensitivity of 88.7 percent for primary HIV infection compared with a sensitivity of 100 percent for the HIV RNA assay. The overall specificity of tests for HIV RNA and p24 antigen was 97.4 percent and 100 percent, respectively.

The authors conclude that the best screening diagnostic test to evaluate patients with suspected primary HIV infection is HIV RNA testing if resources are unlimited, even though the cost of evaluating and providing post-test counseling to false-positive patients is high. An alternative strategy would be to use only assays for p24 antigen, which identify more than 90 percent of infected patients with negative results on HIV antibody tests or indeterminate Western blot.

editor's note: The period of primary HIV infection is directly following HIV transmission. The most common presentation, when symptoms are present, is a mononucleosis-like syndrome with fever, chest pain, lymphadenopathy and skin rash. Less common symptoms include other flu-like manifestations, lymphocytic meningitis and facial paralysis. When this nonspecific picture is present, family physicians must consider the possibility of primary HIV infection. A history of potential exposure should be solicited, and HIV testing should be performed. The presence of HIV antibody during this time may signify a chronic infection. Testing should include an antibody test as well as either p24 antigen or HIV RNA (viral load) testing. Patients are highly infectious during this period of rapid viral replication and high blood virus counts, and appropriate preventive measures should be taken.—r.s.