Test your medicine knowledge with the MKSAP challenge, in partnership with the American College of Physicians.

A 25-year-old man is evaluated in follow-up after HIV testing. He states he has sex with other men and usually uses condoms. He had a negative HIV test result 1 year ago. He feels well today but reports having a flulike illness last week with mild fever, headache, myalgias, and fatigue; these symptoms have resolved. Medical history is unremarkable for sexually transmitted or other infections. Other than taking over-the-counter ibuprofen last week, he takes no medications.

On physical examination, he is afebrile and has small palpable anterior and posterior cervical, axillary, and inguinal lymph nodes. The remainder of the examination is normal.

HIV-1/2 antigen/antibody combination immunoassay is reactive. Result of an HIV-1/HIV-2 antibody differentiation immunoassay is negative for HIV-1 and HIV-2. Result of an HIV-1 nucleic acid amplification testing is positive, with 51,455 copies/mL.

Which of the following is the most appropriate next step in management?

A. Repeat HIV-1/HIV-2 antibody differentiation immunoassay in 6 weeks
B. Saliva rapid HIV testing
C. T-cell subset testing
D. Western blot HIV-1 antibody testing

MKSAP Answer and Critique

The correct answer is C. T-cell subset testing.

This patient should be informed that he has acute HIV-1 infection, and further baseline evaluation of new HIV infection with T-cell subset testing and other appropriate laboratory studies should be pursued. The antigen/antibody combination immunoassay is reactive, indicating the presence of HIV-1 or HIV-2 antibody or HIV p24 antigen. The result on a differentiation immunoassay for HIV-1 and HIV-2 antibodies is negative, suggesting that the initial immunoassay was detecting the presence of viral p24 protein. This is confirmed by the nucleic acid amplification test, which had strongly positive results for HIV RNA, indicating the presence of virus even though the patient did not yet have detectable antibodies. These results are most consistent with acute HIV infection presenting in the “window period” before development of a serologic response. His nonspecific febrile illness the previous week may have represented symptoms of acute HIV infection.

The rapid tests for HIV infection, such as a saliva assay, are convenient for patients but are based on detecting HIV antibodies. They would therefore be expected to yield negative or indeterminate results in this patient because he is presenting in the “window period” of acute infection before antibody development.

The Western blot test is no longer recommended for confirmatory HIV testing. Because this patient has early HIV infection, results of Western blot testing for HIV antibody would likely be negative or indeterminate anyway.

Repeating the HIV 1/HIV-2 antibody differentiation immunoassay at a later time is not necessary because acute HIV infection has been diagnosed on the basis of the high level of viral RNA. Antibody testing results will become positive within a few weeks to a few months, but it would not be appropriate to delay further management for HIV until that time.

Key Point

• Positive antigen/antibody immunoassay, negative antibody differentiation assay, and positive nucleic acid amplification test results are consistent results for patients presenting in the “window period” of acute HIV infection before development of a serologic response.

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