Researchers find easy way to predict outcomes
April 1, 2002
Researchers find easy way to predict outcomes
Clinicians can get answers within a week
Investigators at the National Institutes of Health (NIH) in Bethesda, MD, and the National Cancer Institute have found in a recent study that by looking at early viral decline, a clinician can predict a 12-week outcome among patients starting an antiretroviral regimen.1 The key is to buck conventional wisdom and look at viral load results within a week of treatment.
"If people are suppressed in that first week, then it is maintained," says Michael A. Polis, MD, MPH, a senior investigator with the National Institute of Allergy and Infectious Disease, a part of the NIH. Three different cohorts of treatment-naive patients were observed after initiation of antiretroviral therapy. Researchers checked their viral loads at baseline and at day six of therapy to measure the rate of viral decline, Polis says. "We found it was highly predictive of the 12-week outcome," Polis says. "If you didn’t decrease the viral load about a log in that first week, then it was highly suggestive that persons would not do well long-term."
The research resulted from investigators’ interest in viral kinetics, the rate of drop in the viral load. "What one sees when looking closely is that in the first couple of weeks on therapy, there is the most dramatic drop in HIV in the bloodstream of many individuals," Polis explains. "It’s a two-phase decline with a very rapid drop initially, and then further declines in viral load are much more gradual after the first few weeks or so."
The study examined whether that first rate of decline was predictive of long-term outcomes. They found that if a patient’s viral load dropped 50-fold at day six, the patient almost always responded well to the drug therapy long-term. However, patients who had only a five-fold decrease at day six almost always had a poor response, with their viral load rebounding three months later. By using this single measurement at day six, investigators were able to predict therapy outcome more than 95% of the time. "It gives us a rough measure of a couple of different parameters," Polis says. "One is how efficacious the drug regimen would be against the viral strains that exist in any individual, and secondly, it shows how well a person can tolerate therapy."
Using the six-day viral load test as an indicator of treatment success is advantageous because it’s a simple way to get results much earlier than would be seen with genotyping or phenotyping, Polis says. The findings suggest that people who don’t do well and don’t have a good viral load drop in the first week could have been affected by any of several factors, the most important being that the virus already is resistant to the drugs in the regimen, Polis says. "But also, one of the major things that are a big problem currently is the ability to adhere to therapy because of the side effects associated with the drugs," he says.
Early viral-load testing might indicate that the patient’s reports of diligently adhering to the medication are inaccurate. "This gives us an empirical conclusion so that one can say, I don’t know how it happened, but in the first week, you don’t have a good response to your therapy, and we need to do something about it,’" Polis says. Either the clinician will need to make certain the patient takes the drugs appropriately and can tolerate them, or the clinician will need to find another therapy.
Data mined from two cohorts in the study involved pediatric patients seen in 1995. They received monotherapy of either indinavir or ritonavir. The third cohort was an adult population of treatment-naive patients who received a four-drug therapy of indinavir, nevirapine, AZT, and 3TC, Polis says. "It clearly would be useful to see if these findings would generalize to other regimens as well, but it was consistent across the cohorts, and one suspects it would be the case," Polis says.
Clinicians who observe poor results in their patients after six days of antiretroviral therapy have a variety of treatment options, Polis suggests. "There are 17 drugs currently approved for HIV infection," he says. "We don’t know how long the drugs can remain efficacious, but people are living 20 years or longer with HIV infection, which was unheard of before the combination therapies and the more potent agents."
Currently, the biggest challenge is to find patients a regimen that is tolerable and to which they can more easily adhere, Polis says. "The disease is manageable, and there is no outer limit of life spans for persons with HIV infection under the current therapies, but there’s a fair amount of work that needs to be done to make therapies more tolerant for people," Polis adds.
Reference
1. Polis MA. Reduction in plasma HIV-1 RNA by one week following initiation of antiretroviral treatment correlates with longer-term efficacy. Lancet 2001; 358:760-1765.
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