AIDSWEEKLY Plus; Monday, June 1, 1998
Daniel J. DeNoon, Senior Editor
There have been several reports of infants apparently infected with HIV who were later found to be uninfected. Because these studies used highly accurate tests for the virus - viral isolation or polymerase chain reaction (PCR) analysis - they had been given accepted as evidence that some people are able to fight off HIV infection. The data often is cited as evidence that an AIDS vaccine is possible.
In hopes that further studies of such children would shed light on the immune correlates of protection against HIV - the Holy Grail of AIDS vaccine research - Lisa Frenkel of the University of Washington and colleagues performed careful studies of 42 infants and one mother whose immune systems appeared to have eliminated the virus.
"Our negative studies of 43 cases of suspected transient infection indicate that the phenomenon of transient HIV-1 infection remains to be proven and that most cases suggestive of transient HIV-1 infection are cases of mislabeling of specimens or their contamination in the laboratory," Frenkel and colleagues wrote in the journal Science ("Genetic Evaluation of Suspected Cases of Transient HIV-1 Infection of Infants," Science, 1998;280:1073-7).
The children in the study had been identified in prior studies of mother-to-infant HIV transmission. Cases were reported by the University of Washington, the North Shore Hospital (2), the Pediatric AIDS Clinical Trial Group 076 study (6), the U.S. Centers for Disease Control and Prevention (CDC) New York Perinatal HIV-1 Transmission Study (7), and the Ariel Project (8).
"In these five studies of mother-to-infant HIV-1 transmission, infants had been tested a median of three times by culture or PCR for diagnosis of HIV-1 infection," Frenkel reported.
But instead of clues to the workings of the human immune system, the researchers found only signs of human error.
In 20 cases there appeared to be false-positive PCR tests. In six cases somatic markers showed that the positive and negative samples came from different children - clear evidence of mislabeling. And in the 17 remaining cases there was evidence of specimen mislabeling or laboratory contamination.
"Thus, each case of suspected viremia we investigated appeared to be due to sample mislabeling or laboratory contamination," Frenkel et al. reported.
In the strangest case, PCR tests in different laboratories twice found a mother positive and three times found her child positive. "Although it is improbable, these five virus isolates appeared to have arisen from five separate incidents of specimen contamination or mislabeling," Frenkel et al. wrote. "This case remains enigmatic, however, in that both the mother and infant had strong CD8(+) cytotoxic T-lymphocyte (CTL) responses and lymphocyte proliferation to multiple HIV-1 antigens."
The researchers noted, however, that such immune responses have been detected in other people apparently unexposed to HIV-1. Frenkel et al. recommended that future researchers perform rigorous studies before suggesting that transient HIV infection has occurred. Such studies should include:
* Demonstration, by phylogenetic DNA analysis, of genetically linked viral strains in the donor and in the recipient.
* Use of previously unmanipulated specimen aliquots.
* Confirmation of specimen identification by somatic markers particular to an individual.
* Evaluation of donor and recipient specimens in different laboratories to prevent contamination.
* Confirmation that HIV donor/recipient viruses are linked by PCR analysis of more than one region of the viral genome.
"No case thus far reported has satisfied the viral and host genetic characterization criteria described here for the verification of transient HIV-1 infection," Frenkel et al. observed.
This work was supported by grants from the Pediatric AIDS Foundation, the U.S. Public Health Service, and the Foster Foundation.
The corresponding author for this study is Lisa M. Frenkel, Department of Pediatrics, Division of Infectious Diseases, University of Washington, 4800 Sand Point Way N.E., Box 329500, Seattle, Washington 98105. Email: <lfrenkel@u.washington.edu>.
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