Prevalence of multiclass resistance among antiretroviral experienced HIV-1 infected patients failing therapy

The purpose of this study was to identify changes in the prevalence of multiclass resistant HIV-1 isolates during the time period of genotypic resistance testing in Greece. HIV-1 genotypic analysis was performed after RNA extraction, RT-PCR and population-based sequencing in the protease (PR) and partial reverse transcriptase (RT) region of pol (amino acid positions 35-245). Two hundred thirty nine patients with known treatment histories who had failed therapy (HIV-RNA > 1000 copies/ml) in the time period from March 1999 to June 2000, were studied. Interpretation of the obtained genotype was according to reported algorithms for drug resistance testing. Multiclass resistant isolates (MCR) were defined as those found to be resistant to at least one drug of NRTIs, NNRTIs and PIs. To determine whether the prevalence of MCR HIV-1 isolates changed over time, we assessed the frequency of MCRs in quarters of 4-months each, since the beginning of genotypic drug resistance testing in Greece. At the time of testing, 52% of patients were receiving NRTIs and PIs, 14% NRTIs, NNRTIs and PIs, and 18% were receiving only NRTIs. Resistance to one of the NRTIs was found at a frequency of 89%, to one of PIs at 55%, and to one of NNRTIs at 26%. Resistance to one of NRTIs and PIs was found at 32%, to one of NNRTIs and NRTIs at 5%, and to one of NRTIs, NNRTIs and PIs (MCR) at 18% of the individuals. The frequency of MCR was 4%, 12%, 25% and 22% at; each 4-month period, respectively (P for trend = 0.02). The increasing prevalence of MCRs is due to the extensive use of antiretroviral drugs and has direct; implications in the control of HIV-1 disease, since the proportion of patients with limited treatment options seems to be increasing rapidly.