Tests Find ‘Silent’ AIDS Infections

New research suggests that the standard blood tests for AIDS fail to detect the deadly human immunodeficiency virus in nearly one of every four “high-risk” gay men who practice unsafe sex.

In the startling finding, UCLA researchers isolated the virus which causes AIDS in 23% of a group of Los Angeles-area gay men who repeatedly tested negative for the virus by standard tests.

Before the study, such “silent” HIV infections had been known to occur, but were considered rare.

“The results are very shocking,” said David T. Imagawa, a professor of pediatrics and microbiology-immunology at Harbor-UCLA Medical Center in Torrance and the principal author of the study in today’s New England Journal of Medicine. “We expected, if anything, to find very few (antibody-negative infected) individuals.”

Imagawa said the results re-emphasize the need for gay men, intravenous drug users and others in AIDS risk groups to refrain from donating blood and to practice safe sex--even if they have tested negative for AIDS antibodies. Regardless of antibody test results, blood banks currently try to screen out and eliminate donations from those at risk of being infected.

The team of researchers from UCLA, Northwestern University Medical School in Chicago and Cetus Corp. in Emeryville said they isolated the AIDS virus in 31 of a group of 133 gay men who had tested antibody-negative.

Dangerous Sexual Practices

The researchers sought gay men who they thought were likely to be infected, despite negative antibody tests. Such men continued to engage in anal intercourse with multiple partners and other dangerous sexual practices.

For this reason, the scientists cautioned that their findings could not be generalized to others who have tested negative for AIDS antibodies, many of whom are at lower risk of infection and may never have been exposed to the virus in the first place.

“This is a select group,” Imagawa said. “We cannot provide an estimate of the proportion of (all) HIV infections that do not stimulate measurable antibodies.”

Antibody molecules are proteins produced by the body’s immune system to fight foreign germs, such as the AIDS virus. AIDS antibodies are measured by standard tests called the enzyme-linked immunosorbent assay or “Western blot.”

Antibodies are commonly detected in the blood within several months of HIV infection. But previously a small number of infections had been recognized where the delay was one to three years or more.

In a New England Journal of Medicine editorial also published today, William A. Haseltine of the Dana-Farber Cancer Institute in Boston said the new data may have “encouraging” as well as “disquieting” implications.

The “good news” is that the evidence that some infected men have not developed antibodies may suggest they are somehow warding off the disease. The replication of the AIDS virus “may be spontaneously suppressed by a combination of cellular, viral and immune mechanisms in far more people than has been supposed,” Haseltine wrote. He suggested that physicians could learn how to use medications to similarly “induce prolonged remissions” in individuals who have already tested antibody-positive.

But Haseltine acknowledged that the study raised the “sobering” possibilities that many of the antibody-negative sexual partners of antibody-positive individuals “may actually harbor silent infection” and that the AIDS virus “may be transmitted by blood and organ donors who are silently infected.”

The U.S. Centers for Disease Control estimates that HIV may be transmitted by blood that has tested negative for AIDS antibodies at a rate of up to 1 donation per 40,000. The CDC also estimates that between 1 million and 1.5 million Americans are infected with the AIDS virus.

Another leading AIDS researcher expressed skepticism about the new data, which has not been independently confirmed. The researcher, who requested anonymity, said that related research to be presented next week at the international AIDS meeting in Montreal appears to contradict the UCLA finding of a substantial number of silent HIV infections in high-risk gay men.

“It is such an unexpected result,” the researcher said of the UCLA finding. “If it is true, it is very disturbing. “I would like to see it confirmed by another laboratory.”

The new report is part of the Multicenter AIDS Cohort Study, an ongoing federally funded evaluation of nearly 5,000 gay men from the Los Angeles, Chicago, Pittsburgh and Baltimore-Washington areas. Since 1984 or early 1985, the volunteers have received semiannual exams and blood tests.

Initially, about 50% of the 1,637 gay men from the Los Angeles area tested positive for AIDS antibodies and the rest tested negative, according to the report. Subsequently, the UCLA researchers participating in the project began an intensive effort to isolate HIV from the 133 antibody-negative men who continued to have high-risk sex.

The researchers attributed their ability to find HIV in the blood of 31 of these men to the use of a variation on a standard laboratory culturing method for HIV isolation. These labor-intensive tests to grow the virus in the test tube cost hundreds of dollars each and are usually performed only in research laboratories.

When the standard culture procedure--commonly employed to isolate the virus from antibody-positive individuals--was used, no virus was isolated from antibody-negative gay men. But when the variation on this method was used, the virus was isolated in the 31 men.

According to the report, four of the 31 gay men became antibody-positive 11 to 17 months after HIV was first isolated.

The other 27 men have remained antibody-negative for up to 36 months after the virus was first isolated.

Many of the implications of the new data are not clear. For example, the researchers said they do not know if antibody-negative infected individuals are as infectious as those with positive antibody tests. Individuals with positive AIDS antibody tests presumably have larger amounts of HIV in their bodies than individuals who are infected with the virus but have never tested positive.

“The unfortunate truth is that we are much better at proving who is infected, as opposed to proving that somebody is not infected,” said Dr. Neil Schram, an AIDS specialist at the Kaiser Foundation Hospital in Harbor City and a member of the Los Angeles County Medical Assn. AIDS committee.

Schram said that on the basis of the new data antibody-negative individuals who have engaged in high-risk sexual or intravenous drug use would need ongoing HIV testing. He also said that individuals who have, for example, resumed high-risk sex in a monogamous relationship after repeatedly testing antibody-negative could still be putting their partners at risk for infection.

Dr. Steven M. Wolinsky of Northwestern University Medical School, a co-author of the study, said that he will continue to advise patients that they are “unlikely to be infected” if they have remained antibody-negative for “a prolonged period of time” and have “eliminated activities that would put them at risk for acquiring the virus.”

Wolinsky’s laboratory is in the process of performing another test that can diagnose silent HIV infection, called the polymerase chain reaction, on nearly 3,000 antibody-negative gay men who are part of the national AIDS cohort study. This study, which Wolinsky said should be completed within a year, should provide a more accurate estimate of the frequency of silent HIV infections.