When it comes to fighting the AIDS virus, the sooner patients start taking powerful drug cocktails, the better - even when it comes to side-effects known as toxicities, U.S. researchers reported on Tuesday.
Deaths, the rate of opportunistic infections and side effects all were the lowest in patients who started treatment early - while their immune systems were still relatively intact, the team at the University of Colorado Health Sciences Center and the Centers for Disease Control and Prevention found.
“Earlier was better in almost everything we looked at,” said Dr. Kenneth Lichtenstein of the University of Colorado. “If you stayed on treatment and started earlier, you had the best outcomes,” Lichtenstein said in an interview.
He said current guidelines that recommend delaying therapy are based on incorrect assumptions that starting drugs early worsens toxicity, because his study found that early treatment reduces toxic side-effects.
Lichtenstein and colleagues used the medical records of 2,304 HIV-positive patients in eight U.S. cities who were part of a larger HIV Outpatient Study between 1996 and 2005.
They looked for three common treatment-related toxicities - kidney insufficiency, a type of nerve damage known as peripheral neuropathy, and a form of wasting known as lipoatrophy.
They broke the patients down into five groups based on the number of CD4 T-cells they had - known as the CD4 count. As HIV infection worsens, the virus attacks these immune cells and the count goes down.
All the patients were on drug cocktails known as HAART or highly active antiretroviral therapy. These three and four drug mixes can keep patients healthy if taken properly.
HIGHER CELL COUNTS
Patients are generally told to start HAART at a CD4 cell count of 200 or below. But some patients started treatment with cell counts of 350, 500 or higher.
Those patients who started treatment at CD4 counts above 350 were at least 60 percent less likely to develop kidney insufficiency, 30 percent less likely to have peripheral neuropathy, and 60 percent less likely to develop lipoatrophy than patients who started at a CD4 count of 200 cells or below, the researchers told the Conference on Retroviruses and Opportunistic Infections.
Lichtenstein said it appeared the drug was the most active in and around cells when there were the fewest CD4 cells.
Inflammation seems to be an important factor, he said. “The state of inflammation associated with disease brings up the toxicity,” Lichtenstein said.
This suggests there is no reason to delay HAART treatment, and no reason to delay getting tested for HIV, Lichtenstein said.
Drug companies have simplified the regimens so that patients can often take just two pills a day. In the past patients often had to juggle 20 pills, taken at specified times of day, some with meals.
The side-effects also were debilitating, ranging from diarrhea and nausea to serious organ damage.
And there were fewer choices of drugs, so patients often were wise in hesitating to start therapy until they really “needed” it, because if the virus became resistant to a drug, a patient had few others to turn to.
“Now there are four classes of drugs, soon to be five classes,” Lichtenstein said. These include the old-line reverse transcriptase inhibitors, such as AZT, the protease inhibitors, the non-nucleoside reverse transcriptase inhibitors, fusion inhibitors and entry inhibitors.
They all attack the virus at different points of its life cycle. None destroy it but they can suppress it almost completely if taken in the right combinations.
Revision date: June 11, 2011
Last revised: by Sebastian Scheller, MD, ScD