523 MDR-1 Genetic Polymorphism Does Not Influence the Response to Antiretroviral Therapy with Protease Inhibitors in Drug-naïve Patients with HIV Infection M. Nasi1, V. Borghi2, M. Pinti1, C. Bellodi1, E. Lugli1, C. Mussini2, R. Esposito2, A. Cossarizza*1 1Univ of Modena, Italy and 2Univ Hosp, Modena, Italy
Background: P-glycoprotein (P-gp) is a membrane-localized transporter, codified by the gene MDR1, that pumps out from cells several drugs, including HIV-protease inhibitors (PI). A polymorphism exists in exon 26 (C3435T) that can influence the response to PI or non-nucleosidic reverse transcriptase inhibitors (NNRTI). Thus, we investigated this polymorphism in 2 groups of drug-naïve HIV+ Caucasian patients (pts).
Methods: 149 HIV+ pts were retrospectively evaluated; 105 took one PI (indinavir or ritonavir) with 2 nucleosidic reverse transcriptase inhibitors (NRTI), 44 took NNRTI (efavirenz or nevirapine) associated with 1 or 2 NRTI. MDR1 genotype was analyzed as described, correlation with CD4 cell count and plasma viral load was performed after 3 and 6 months (mos) of treatment. Statistical analysis was done using Kruskal-Wallis test and unpaired Student’s t-test with Welch’s correction. Adherence was evaluated by a self administered questionnaire.
Results: At the beginning of therapy, in the group of pts taking NNRTI, CD4 cell count was higher and viral load lower (p < 0.01 in all cases); adherence was optimal in both groups. Either in PI- or NNRTI-treated pts, therapy significantly increased CD4+ cell count and decreased plasma viral load (undetectable in almost all cases). MDR1 genotype frequency in all HIV+ pts was identical to that previously described in Caucasians. In PI-treated pts, no significant differences were found among individuals with different MDR1 genotype as far as the increase in CD4+ T-cell number or decrease in viral load were concerned. In NNRTI-treated pts, those with TT genotype showed the highest rise in CD4-count either after 3 mos (177 ±51 cells/uL; those with CC genotype had 89 ±24, p = 0.10; those with CT had 79 ±28, p = 0.08) or after 6 mos (202 ±47 , those with CC genotype had 145 ±40, p = 0.36; those with CT had 124 ±24; p = 0.15).
Conclusions: MDR1 polymorphism does not influence response to PI-therapy in treatment-naïve HIV+ pts. Concerning pts taking NNRTI, our data, even if not statistically significant because of the relatively small number of individuals, fully agree with those of Fellay. However, caution is essential when interpreting genetic data, as other variables might influence antiretroviral treatment, including genetic polymorphisms of phase I or II enzymes, or of other transporters than MDR1.
