New Strategy May Help to Analyze Antiretroviral Drug Resistance

European researchers have developed a stepwise methodology that could be useful in analyzing genotypic predictors of resistance to antiretroviral drugs, according to a new report.

To create this strategy, Dr. Francoise Brun-Vezinet, from Bichat-Claude Bernard Hospital in Paris, and colleagues analyzed data from 175 HIV-infected patients treated with abacavir in a major multicenter trial. Using statistical methods, the authors were able to quantify the impact of nucleoside analogue resistance mutations on the viral response to abacavir.

The strongest link between the virologic response and mutation number was found with six mutations of the reverse transcriptase gene, the investigators report in the August 15th issue of AIDS. The mutations were located at codons 41, 67, 210, 215, 74 and 184 of the reverse transcriptase gene.

Patients with three or fewer mutations were classified as having no evidence of resistance and experienced a drop in viral load of -1.64 log10 copies/mL. In contrast, the changes in viral load for patients with four mutations (possible resistance) and those with five or six mutations (resistance) were only -0.69 log10 and -0.19 log10 copies/mL, respectively.

Multivariate analysis showed that this six-point score was an independent predictor of virologic response to abacavir, the researchers point out.

"We have developed a new approach for correlation study between genotype at baseline and virological response to an antiretroviral drug," the investigators state. "This strategy is particularly suitable for studies involving patients receiving a wide variety of different drugs besides the molecule being analyzed."

08/27/03

AIDS 2003;17:1795-1802.