They call for better detection and improved drugs to eradicate the virus
The best AIDS drugs are still not good enough. Scientists at Jefferson Medical College have found evidence for the first time of actively replicating HIV in the bloodstream of patients taking the most powerful anti-AIDS virus drugs available.
Scientists knew that the combination of drugs known as HAART, highly active antiretroviral therapy, did not eradicate the AIDS virus, despite the fact that the virus could not be detected by conventional means in the patient’s blood. But they thought that the drugs had at least arrested the virus from replicating. No one had been able to find active virus in the blood of patients still on the drugs.
Roger J. Pomerantz, MD, professor of medicine, biochemistry and molecular pharmacology, and chief of the division of infectious diseases at Jefferson Medical College of Thomas Jefferson University in Philadelphia, and his co-workers examined 22 HIV-infected patients taking HAART. Using ultrasensitive molecular techniques, he and his team found evidence of active virus in the blood plasma of every patient.
The researchers report their results Nov. 3 in JAMA, the Journal of the American Medical Association.
"No one has shown in patients taking these drugs that the virus spills out of the immune cells it normally infects and into the blood, possibly infecting other cells," says Dr. Pomerantz, who also directs Jefferson’s Center for Human Virology. "There had not been replication previously detectable in the bloodstream or in genital fluids.
"It teaches us something if we’re going to eradicate the virus," he says. "We need to be able to stop replication before we think about eradication."
Dr. Pomerantz calls for better detection methods as well.
"In the era of HAART, a lot of the new technologies in laboratories need to be more generalized because now in many cases you’re dealing with low levels of virus."
The researchers looked at people taking HAART, a combination therapy of protease and reverse transcriptase inhibitors, and had no detectable virus in their blood by the best available clinical assays. All patients had fewer than 50 copies of virus per milliliter of blood plasma. Using extremely sensitive techniques, they found active virus in every person, whether the patient had been taking the drugs for months or years.
A recent study of patients on HAART and a drug called IL-2 showed that when the drugs were halted, all patients’ viruses returned to earlier levels. "Scientists had thought there was no replicating virus – that it was latent and inactive while the patient was taking drugs," he says. "It makes sense that patients will grow more virus and develop symptoms again once drugs are stopped. We were unable to find anyone without replicating virus. We showed that not only can the virus infect cells close to where the viruses are produced, but it also could spread and possibly infect other cells."
Dr. Pomerantz’s group also found active virus in the seminal fluid of 10 patients. They previously reported that the AIDS virus is still present in a potentially infectious inactive, "latent" form in the semen of infected men taking HAART, even when no measurable virus could be found in the blood.
"Now we have two things we’re dealing with in these patients: residual HIV that’s replicating and residual HIV that’s latent," he says. He’s using these new findings in ongoing clinical studies to attempt to eradicate HIV in certain patients.
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