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To demonstrate the spontaneous clearance of HIV infection, two points must be established: a confirmed diagnosis of HIV infection early in life, and the absence of infection in the child at the present time. In the case reported by Bryson et al., the latter point seems more likely, given the five years of follow-up. However, the use of PCR to test for HIV-1 RNA in plasma may help detect low-level viremia produced by cells that are inaccessible by blood sampling.
The diagnosis of infection in this infant was based on two positive HIV cultures on days 19 and 51; a third culture, on day 33, was negative. In this very unusual clinical situation, direct PCR studies of uncultured peripheral-blood mononuclear cells could have confirmed the diagnosis and allowed further sequencing and accurate nucleic-acid comparisons,3 averting possible artifacts due to culture. Since cryopreserved peripheral-blood mononuclear cells were available for extensive genetic studies on day 19, they could be used to test for HIV-1 proviral DNA by PCR. A negative result would diminish the message of hope conveyed by this unique observation.
Anne Krivine, M.D.
Pierre Lebon, M.D.
Hôpital Saint Vincent de Paul
75674 Paris, France
References
It has been well documented that maternal-to-fetal engraftment of T cells occurs regularly in infants born with severe combined immunodeficiency.1 This phenomenon may be a factor in the transmission of HIV. That T cells transferred from mother to infant are viable is shown by their ability to produce graft-versus-host disease.1 Furthermore, in babies with severe combined immunodeficiency, maternal cells have been shown to be tolerated for up to 12 months after birth.1
It is therefore possible that the HIV detected on days 19 and 51 in the infant described by Bryson et al. was that found in maternal cells. Only small numbers of maternal cells may be transferred to the fetus, resulting in the negative results of early PCR testing. Subsequently, such cells would proliferate in response to the infant's lymphocytes, resulting in increased expression of HIV. In an immunocompetent host, the maternal cells would be cleared. The result would be the apparent clearance of HIV infection in the host. The presence of HIV in maternal cells could also explain why a detectable proliferative response to HIV-1 was not found.
Genetic studies were performed to ensure that no error was made in sample labeling. Were these tests sufficiently sensitive to exclude the possibility that a low level of maternal DNA was present? Since the child was male, determination of the karyotype of the HIV-expressing cells could provide the answer.
Mark Gompels, M.B., B.S.
Gavin Spickett, D.Phil.
Newcastle General Hospital
Newcastle-upon-Tyne NE4 6BE, United Kingdom
Anne Curtis, Ph.D.
Newcastle University
Newcastle-upon-Tyne NE2 4HH, United Kingdom
References
To the Editor: We based the diagnosis of HIV-1 infection in this infant on the presence of cultured virus in samples of peripheral blood obtained from the infant on two separate occasions — an approach that is consistent with the guidelines established by the National Institutes of Health AIDS Clinical Trials Working Group and the Centers for Disease Control and Prevention.1,2,3 DNA PCR assays with peripheral-blood mononuclear cells have entailed more problems with potential laboratory contamination in other studies, although we have found the assay to be sensitive and specific.4 The infant had a positive result on DNA PCR testing, with a very low number of copies (3 per microgram of DNA), on one occasion and positive cultures on two occasions; only 1 in 1 million cells was infected. This result indicates that the infant had a very low viral load, as compared with other infected infants we and other investigators have followed sequentially during the first few months of life.4,5 We would have liked to perform all possible tests on this child, particularly on the early occasions; we were limited, however, by the small specimens available for retrospective testing and the need to gain the maximal amount of information.
We agree with Dr. Gompels and his colleagues that it is possible that infected maternal cells persisted in the infant's circulation. If the maternal cells were proliferating in the infant for several months, as the authors suggest, it would still not explain why the infant's own cells were not infected. The mother's very low viral load as evidenced by our inability to culture virus from her blood for over a year, and the presence of cell-free virus in the plasma of the infant at the time of the second positive culture (suggesting replication) make this possibility less likely.
We would also like to correct a statement in our article. Although we state that "some of the maternal HIV-1 sequences were closely related to the principal sequence from the child's samples" (page 835, righthand column, lines 35 to 37), as we state elsewhere in the article, it is not possible at this time to establish a relation between the mother's virus and that of the infant. This fact has no bearing on the central conclusion of our report; the infant was infected, as evidenced by the isolation of identical virus on two different occasions, and then became free of virus. The possibility that the virus was maternally derived has not been formally confirmed and is currently being addressed.
Yvonne J. Bryson, M.D.
Irvin S.Y. Chen, Ph.D.
UCLA School of Medicine
Los Angeles, CA 90024-1752
References
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