Correspondence

Transient HIV Infection in Infants

N Engl J Med 1996; 334:801-802March 21, 1996

Article

To the Editor:

Descriptions of infants with reported clearance of human immunodeficiency virus (HIV) infection are both provocative and of some concern.1-3 They raise a number of scientific questions that are difficult to answer on the basis of our current understanding of HIV transmission. Because these reported cases are critically important to understanding HIV transmission and clearance and have implications for the therapeutic control of HIV infection, it is essential that each reported case be fully documented according to criteria acceptable to the entire scientific community.

On October 5, 1995, an international workshop sponsored by the Pediatric AIDS Foundation was held in Oxford, England, to develop uniform criteria for use in reports of infants who have initial diagnoses of HIV infection but do not subsequently demonstrate any evidence of either such infection or an antibody response to HIV. Because other groups have defined infected and uninfected infants, this workshop focused on developing criteria to be used in defining transient HIV infection in infants.

Transient HIV infection in an infant should be defined as any combination of a positive polymerase-chain-reaction (PCR) assay or viral cultures of blood samples obtained on two separate occasions (with at least one positive culture), excluding tests of cord blood, but with no HIV infection evident subsequently on either culture or PCR and no antibody to HIV on tests of two blood samples. In addition, the genetic relatedness of the viruses in the mother and the infant must be established by either heteroduplex analysis or a comparison of viral sequences using previously defined criteria.4,5 The documentation should include studies of at least two HIV-positive samples obtained from the infant at different times and at least one HIV-positive sample from the mother.

Infants who do not meet these criteria because the genetic relatedness of the viruses from the mother and the infant cannot be determined should be considered as having presumptive, but not transient, infection. Infants who test positive for HIV by PCR or culture in only a single sample and who have two negative antibody tests to HIV at an age greater than 18 months should simply be classified as having ambiguous test results and should not be considered for further evaluation.

These suggested criteria are not meant to prevent HIV-exposed infants from being evaluated in greater detail, but are intended to provide a more meaningful basis for determining whether infants who are considered to be HIV-infected can have clearance of their infections with no evidence of an immune response.

Andrew McMichael, M.D.
John Radcliffe Hospital, Headington, Oxford OX3 9DU, United Kingdom

Richard Koup, M.D.
Aaron Diamond AIDS Research Center, New York, NY 10016

Arthur J. Ammann, M.D.
Pediatric AIDS Foundation, Novato, CA 94949

5 References

1
Bryson YJ, Pang S, Wei LS, Dickover R, Diagne A, Chen ISY. Clearance of HIV infection in a perinatally infected infant. N Engl J Med 1995;332:833-838
Full Text | Web of Science | Medline

2
Bakshi SS, Tetali S, Abrams EJ, Paul MO, Pahwa SG. Repeatedly positive human immunodeficiency virus type 1 DNA polymerase chain reaction in human immunodeficiency virus-exposed seroreverting infants. Pediatr Infect Dis J 1995;14:658-662
CrossRef | Web of Science | Medline

3
Roques PA, Gras G, Parnet-Mathieu F, et al. Clearance of HIV infection in 12 perinatally infected children: clinical, virological and immunological data. AIDS 1995;9:F19-F26
CrossRef | Web of Science | Medline

4
Korber BT, Learn G, Mullins JI, Hahn BH, Wolinsky S. Protecting HIV databases. Nature 1995;378:242-244
CrossRef | Web of Science | Medline

5
Delwart EL, Shpaer EG, Louwagie J, et al. Genetic relationships determined by a DNA heteroduplex mobility assay: analysis of HIV-1 env genes. Science 1993;262:1257-1261
CrossRef | Web of Science | Medline

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