Jan. 17, 2007 A World Health Organization (WHO) plan to track transmitted resistance to HIV drugs in Botswana could fail because the threshold the organization has set is too high, according to new UCLA research.
The authors of the study, which will be published Jan. 17 in the peer-reviewed online journal PLoS ONE (), based their research on the WHO's Botswana antiretroviral program, which began in 2002 and now treats some 42,000 patients. The program's goal is to treat 85,000 patients by 2009, roughly 30 percent of all those infected in Botswana.
As greater numbers are treated, the likelihood that a small percentage of patients will develop strains of HIV that are resistant to antiretroviral drugs increases. These patients may then transmit the drug-resistant strains to others, but the rates at which this may happen are unclear. The WHO surveillance system is intended to detect transmitted resistance exceeding a 5 percent threshold by 2009, though officials with the organization have not determined at what point this threshold might be reached, if at all.
According to the UCLA study, the WHO's detection test is based on a sophisticated statistical method, but the 5 percent detection threshold is an arbitrary one. Study co-author Sally Blower, UCLA professor of psychiatry and biobehavioral sciences and a member of the UCLA AIDS Institute, said the WHO threshold was primarily based on guesswork.
"They did not make any mathematical predictions on how long it would take to get to their threshold," Blower said. "Essentially, they've guessed what would happen. They should have done things on a more quantitative basis."
Blower and co-author Raffaele Vardavas, a postdoctoral fellow in Blower's research group, developed a mathematical model that traces the random evolution of drug-resistant strains of HIV in Botswana through 2009. They found that drug resistance would indeed emerge but likely at a much slower rate than the WHO anticipates, and the organization would not be able to detect it.
Though easy to implement, the WHO's statistical test would detect transmitted resistance only after it has reached 5 percent, and that threshold would likely not be reached by 2009 unless the drug-resistant strains of the virus are extremely transmissible, the authors said.
The authors note that while the WHO's monitoring plan requires a small sample size and is relatively inexpensive, it may not be entirely cost-effective at the early stages of the treatment program due to the high threshhold. Instead, they suggest that checking for transmitted resistance early this year and dropping the threshold to about 3 percent would present a better picture of the situation in Botswana. Although a lower threshold requires a larger sample size and is therefore more expensive, it is much more likely to detect transmitted resistance and therefore would be more useful.
"If transmitted resistance is found to be at or above 3 percent, then repeating the WHO's test in the next scheduled occasion using a 5 percent threshold value would provide more information as to how quickly transmitted resistance is increasing in Botswana," Vardavas said. "Although this would be more expensive, it would probably be more cost-effective than the current strategy."
The National Institute of Allergy and Infectious Diseases funded the study.
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