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3. Diagnosis
Early diagnosis of vertically acquired HIV infection has important implications for decisions concerning initiation of prophylactic and therapeutic medications, medical follow up, and management of intercurrent illnesses. Unfortunately standard HIV serological tests, including enzyme linked immunosorbent assay (ELISA) and Western blot immunoassay, are not useful in the diagnosis of HIV infection during infancy because of the confounding presence in infants' blood of transplacentally derived maternal antibody. Detectable anti-HIV antibody may persist for 18 months or longer in some cases.
Diagnosis of HIV infection during infancy by physical examination alone is difficult. Generalized lymphadenopathy and hepatosplenomegaly occur commonly among HIV-infected infants, but these findings are neither sensitive (particularly during the first three months of life) nor specific for the diagnosis.
Hyperimmunoglobulinemia is a sensitive but non-specific indicator of HIV infection during the first six months of life. Some HIV-infected infants, especially those who develop symptomatic disease at an early age, have hyperimmunoglobulinemia from the time of birth; more commonly, it develops over the first few months of life. Because of transplacental passage of maternal IgG, hyperimmunoglobulinemia G alone is a finding of doubtful significance in the HIV exposed infant.
In the U.S., the HIV DNA polymerase chain reaction (PCR) assay is used most widely for diagnosis of HIV infection during infancy. Testing generally should be performed in the immediate newborn period, at one to two months of age, and at age three to six months. Just as is the case with HIV culture, false-negative test results sometimes are observed in the newborn period, but the sensitivity of HIV DNA PCR at or after one month of age is excellent. Because PCR is used to amplify minute amounts of specific DNA by many orders of magnitude, and even the slightest contamination can produce false-positive tests results, a single positive HIV DNA PCR test result should be interpreted with caution. Any infant with a positive test result should be re-tested immediately.
For purposes of clinical decision-making, an infant less than 18 months of age is considered HIV-infected if he/she is known to be HIV-seropositive, or was born to an HIV-infected mother, and has positive results on two separate direct tests for HIV (i.e., HIV culture, PCR, or p24 antigen detection) performed on separate blood specimens. Cord blood should not be used. An infant also is considered HIV-infected if he/she meets the CDC surveillance case definition for AIDS. Infection can be reasonably excluded by the presence of at least two negative HIV PCR tests, both of which are performed at or after one month of age, and one of which is performed at or after four months of age. Infection is excluded definitively in such an infant by the disappearance of anti-HIV antibody (i.e., seroreversion) by 18 months of age in the absence of hypogammaglobulinemia.
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