ASSOCIATION OF SPECIFIC GENETIC MARKERS OF THE HOST WITH THE RESPONSE TO ANTIRETROVIVAL THERAPY IN HIV POSITIVE PATIENTS
Keywords:
HIV infection, High Active Antiretroviral TherapyAbstract
The aim of our study was to investigate the influence of various host genetic markers on the efficacy and safety of antiretroviral drugs in the Macedonian population. The analyzed cohort consisted of 361 HIV patients, 333(92.2%) male and 28(7.8%) female, with mean age at diagnosis of 33.6 years (range 4-65 years). The median follow-up after diagnosis was 4.3 years (0-29.5 years), within which 12 patients died. As expected, the antiretroviral treatment had a dramatic effect on reducing the viral load, from 4.702x104 (range 0-109) to 0 between their first and last PCR test (p=2.2x10-16).
We determined the allele frequencies of CYP2D6 and stratified them between HIV patients who never achieved undetectable viral load (UVL) and those who demonstrated UVL at least at one PCR test. Based on the CYP2D6 status, patients were categorized as Extensive Metabolizers (EM) and 16 as Poor Metabolizers (PM). We found that neither CYP2D6 allele or allele combination, nor the EM/PM status were significantly associated with achieving UVL (p=0.2). When adjusted for age at diagnosis and sex in a logistic regression model, neither CYP2D6 alleles nor EM/PM phenotype reached a statistically significant level of association with achieving UVL, except for the trend for CYP2D6 allele *6 to lower the odds of reaching UVL, OR=0.16 (95CI 0.02-0.974).
The results from our preliminary analysis indicate much higher frequency of CYP2D6 EM vs. PM phenotype in the Macedonian population and no significant influence on the treatment efficacy in terms of achieving UVL.
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