The more sophisticated testing, now used by the nation's blood banks, would be a distinct improvement over routine antibody tests, which cannot detect the virus for up to two months post-infection, researchers say.
Nucleic acid screening of pooled blood can boost the total number of people diagnosed by about 10 percent, said the University of North Carolina at Chapel Hill physician who led the study. Increased costs would be minimal -- about $2 per test, or $4,109 for each new case diagnosed, figures that pale by comparison with the financial and human burden of missing a case or missing the opportunity to prevent further HIV transmission.
"The acute stage of the infection is almost never diagnosed in clinical practice and is always missed by routine antibody tests," said Dr. Christopher D. Pilcher, assistant professor of medicine at the UNC School of Medicine. "So without this type of testing, we miss the time when we know that people have by far the most virus in their blood and are at their most infectious. If we can catch infected people during the first weeks when routine antibody tests are still negative, we can help them avoid spreading HIV to their husbands, wives, unborn children or other intimate partners."
Findings from the study are being presented at the World AIDS Conference in Barcelona, Spain, beginning July 6 and also will appear in the July 10 issue of the Journal of the American Medical Association.
Besides Pilcher, UNC authors are Drs. Peter A. Leone and Joseph J. Eron of medicine, Marlene Smurzynski of epidemiology and Drs. Amy L. Peace-Brewer and Susan Fiscus of microbiology and immunology. Other authors are J. Todd McPherson and Juanita Harris of the N.C. State Laboratory of Public Health's Serology/Virology Laboratory, Leone and Judy Owen-O'Dowd of the N.C. Department of Health and Human Services' HIV/STD Prevention and Care Branch and Dr. Charles B. Hicks of Duke University's Department of Medicine.
In a study published in the Journal of the American Medical Association last October, Pilcher and colleagues showed that people who contracted the AIDS virus could pass it on to others after a single sexual contact, within a week or two of picking it up themselves. In some cases, viral transmission to a sex partner occurred before the source developed any of the temporary flu-like symptoms characteristic of the first weeks of HIV infection.
In their new work, researchers focused on 8,505 people who visited 110 publicly funded testing sites in North Carolina for routine HIV testing and counseling in August and December of 2001. Of the 8,194 subjects who had not previously tested positive for HIV and also had enough serum for additional evaluation, investigators found 39 with long-term HIV infection. Then, using specimen pooling and nucleic acid testing, the team found four additional people -- all women -- with acute HIV infection among the 8,155 people whose antibody tests were negative.
Laboratory workers draw off portions of serum from 10 antibody-negative specimens, combing these into a single pool representing the 10 specimens, Pilcher explained. Then, portions of each of the pools of 10 are drawn and combined to make pools of 90.
By testing the largest pools and then, if necessary, the smaller ones, laboratory staff can see which pools are negative for HIV and thereby eliminate all individual testing of specimens from groups showing no virus, the physician said. If a smaller pool is found to contain the virus, then each specimen gets tested individually through what's called a polymerase chain reaction (PCR).
"One important thing we proved with this new work was that a significant number of very contagious infections are being missed by routine antibody testing," he said. "The nucleic acid testing, or PCR, detects patients who may represent a public health threat and who would ordinarily get a falsely reassuring 'negative' test result. We hope that this type of testing can help us cut the risk for the unsuspecting partners of acutely infected patients.
"In addition, these people can potentially benefit themselves if we know to start them quickly and aggressively on anti-retroviral treatment," Pilcher said. "Several very exciting but preliminary studies have shown recently that early treatment in this way may improve their long-term prognosis."
Numerous medical scientists had thought the pooling technique could uncover individual new acute HIV cases among large groups of at-risk people, but the UNC group and their colleagues are the first prove it in practice.
"The reason this wasn't done before was that there are extraordinary difficulties in doing this kind of collaborative research effort in clinical public health settings," the physician said. "That we were able to do it is a credit not only to the UNC faculty and staff involved, but also to the people at the state's department of health and laboratory of public health who have shown an ability to think outside the box with regard to HIV."
Note: Pilcher can be reached at (919) 966-2536 or (919) 216-3692 (pager) until July 5. During the conference, from July 6-12, he will stay at the Hotel Royal in Barcelona. Leone, who will not attend, can be reached at 1-888-581-6257.
By DAVID WILLIAMSON
UNC News Services
Journal
JAMA