Researchers have devised a strategy for determining how long a person has been infected with HIV. And the finding, said one of the investigators, could revolutionize the approach to understanding early HIV infection, developing appropriate early treatments and estimating the incidence of HIV infection on a national scale.
The multi-institutional finding was reported in the July 1 special issue of JAMA. The general diagnostic approach will also be discussed in a number of sessions at the 12th World AIDS Conference in Geneva next week. The study was conducted by researchers at eight public and private institutions. The new tactic addresses what has been a major obstacle in the study and treatment of patients with HIV infection: the inability to determine how long a person has been infected with the virus, particularly in the early stages of infection.
Diagnosis is made when blood tests indicate that a person either carries the HIV virus or has antibodies to the virus. But these tests do not distinguish infection that occurred 10 days previously from infection that occurred 10 months before. As a result, scientists have not been able to study and tailor treatment to people with the earliest stages of the disease.
The researchers set out to overcome this roadblock. They modified the existing HIV test, called an enzyme immunoassay, to make it less sensitive than the original version. They then administered both tests to 579 people with HIV or AIDS. The result was that some people reacted only to the more sensitive form of the test. And these people, the researchers determined through subsequent study, had a more recent infection.
"This is the first test we've had that sensitively distinguishes patients with the very early stages of HIV from those with more advanced disease," said Margaret Chesney, PhD, a UCSF professor of medicine and co-director of the Center for AIDS Prevention Studies, part of the UCSF AIDS Research Institute (ARI) and a co-author of the study. "Previously, we've relied on declining CD4 T-cell counts to indicate duration of infection, and that approach is very imprecise."
"The new strategy empowers us to identify the people who are candidates for early, aggressive therapy," she said. "It is a remarkable development by Drs. Janssen and Busch [the lead and senior authors of the paper]. It should be heralded as a major breakthrough in HIV care."
"We anticipate that coming out of the 12th World AIDS conference there will continue to be a very strong recommendation for early comprehensive treatment for people who have recently been infected," she said. "The missing link was being able to determine if a person was in the early stage of infection."
"Some of our most important breakthroughs are elegant in their simplicity," Chesney reflected.
The modified form of the enzyme immunoassay test, currently available only in certain locations, will be used routinely by the San Francisco Department of Public Health STD Clinic. Patients identified as having early stage HIV are being referred to the UCSF-affiliated San Francisco General Hospital's Options Project which offers innovative treatment strategies for early HIV infection.
Chesney is an investigator at the Options Project. "Being able to easily and efficiently identify people recently infected with HIV would greatly assist researchers in tracking the spread of the disease," said Chesney, "as knowledge of recent infection provides data on HIV incidence, and is critically needed for monitoring changing patterns of HIV transmission."
The 12 co-authors of the study include first author Robert S. Janssen, MD, of the Centers for Disease Control and Prevention, senior author Michael P. Busch, MD, PhD, of the Blood Centers of the Pacific, Irwin Center and an assistant clinical professor of laboratory medicine at UCSF. Other UCSF co-authors included Chesney and Frederick M. Hecht, MD, a assistant clinical professor of medicine, and James O. Kahn, MD, an associate clinical professor of medicine, both of the UCSF-affiliated San Francisco General AIDS Program.
Other institutions involved include the National Reference Laboratory for Infectious Diseases; the Viral Epidemiology Branch of the National Cancer Institute; Boston Biomedica; the Medical Research Centre, Port-of-Spain, Trinidad; and the University of Maryland School of Medicine.
Journal
JAMA