Newer, more sensitive HIV antibody tests producing false-positive results in uninfected infants

Uninfected infants of HIV-positive mothers may have ‘false-positive’ HIV antibody test results up to 18 months after birth if newer, more sensitive fourth-generation antibody testing assays are used, according to paediatricians from the United Kingdom writing in the May 31^st edition of AIDS. They suggest that these assays are still detecting maternal antibodies and that their use is leading to “anxiety and confusion.” Rather than using fourth-generation antibody tests, the investigators recommend that paediatricians should use older, less sensitive assays.

It is currently recommended that infants have three tests to look for HIV’s genetic material in the first six months of life to determine if they have been infected with the virus, and the investigators suggest that guidelines should be revised and that a fourth test to look for HIV’s genetic material should be undertaken after six months “to optimize diagnostic evaluation.”

There is a significant risk of mother-to-child transmission of HIV. But the use of antiretroviral therapy during pregnancy, appropriate interventions during labour, and, in countries like the UK where safe alternatives are available, not breastfeeding, can reduce this risk to less than 2%.

Current British HIV pregnancy guidelines recommend that a series of diagnostic tests should be undertaken to determine the HIV infection status of the infants of HIV-positive women. These should include three HIV proviral DNA PCR conducted at birth, and again when the child is six and twelve weeks old. Infants are also recommended to have an HIV antibody test when they are 18 months old. Antibody testing is delayed to this time point as infants can retain maternal antibodies to HIV for a prolonged period after birth.

Newer, fourth-generation HIV antibody tests with enhanced sensitivity and specificity, have shown value in the earlier detection of HIV in adults. One such assay, the Greenspan Plus HIV Antigen – Antibody, reduces the window period between infection with HIV and the appearance of antibodies by four or five days compared to third-generation tests, and in the first six months of its use at St Mary’s Hospital in London, three adults who tested negative using the older assay were, in fact, found to be HIV-positive.

But the use of fourth-generation assays is more problematic in infants. The authors report that they used the test on 18 children after three consecutive HIV PCR test results. Eight of the infants were antibody negative using the most recent assay, but ten tested positive. These infants were tested again using the fourth-generation assay a few months later, and nine were found to be HIV-negative. The remaining child was not available for repeat testing, but does not show any clinical signs of HIV infection.

“Our experience suggests that using newer assays with enhanced sensitivity can be problematic in testing infants of HIV-infected mothers because they predictably appear to detect maternal antibody in the child for significantly longer than previous assays,” write the investigators. They add that it is important for doctors and parents to be aware of this issue “to avoid anxiety and confusion.”

They suggest that guidelines should be revised regarding the testing of HIV-exposed infants. A fourth HIV PCR test should be considered after six months, and if an HIV antibody test at 18 months is used, it should “be undertaken with a standard assay rather than an assay of enhanced sensitivity for antibody detection.”