Van Dyke, MD, Dawn Sokol, MD, Cheryl A. associated with a decrease in viral failure after 12 weeks on a ZDV-containing HAART regimen (P = 0.017). Conclusion No increase was seen in the rate of viral failure after HAART associated with the presence of resistance mutations at baseline. This paradoxical result may be due to adherence, replicative capacity, or ZDV hypersusceptibility to the new regimen. Background Nucleoside reverse transcriptase inhibitors (NRTI) OSI-027 were the first antiretroviral drugs available and continue to be Rabbit Polyclonal to RUNX3 a component of anti-retroviral therapy (ART), despite the emergence of drug resistance over time. Few studies have investigated the role of pre-existing drug resistance and response to therapy in children [1-4] compared to comparable studies in adults [5,6]. The largest published drug resistance study of HIV-infected children found a high rate of main mutations associated with resistance to zidovudine (ZDV), didanosine (ddI) and zalcitabine (ddC), but concluded that none of the baseline drug mutations were associated with a higher rate OSI-027 of virologic failure . It is possible that HIV drug resistance may evolve differently in children because of differences in pharmacokinetics in children, fewer drug options, and higher viral burden, especially in younger children [7, 8] and unique difficulties to therapy compliance. Pediatric AIDS Clinical Trials Group (PACTG) 338 was one of the first clinical trials to evaluate highly active anti-retroviral therapy (HAART) which included a protease inhibitor, ritonavir (RTV), in children . We investigated the role of baseline HIV drug resistance mutations and response to therapy. Results There were very few main resistance mutations to PIs in this PI-na?ve population, although 88% of the children had polymorphisms that included secondary minor resistance mutations. The most frequent secondary PI mutations were at codons 63 (78%), 77 (37%), 36 (17%) and 10 (12%) (data not shown). Only two children experienced a main PI resistance mutation (V82A). Other PI mutations (71, 33 and 20) were present in less than 10% of the study subjects. The most common NRTI mutations occurred at codons 215 (66%), 41 (42%), 67 (37%), 210 (33%), 70 (32%), 69 (22%), 118 (21%) and 219 (21%). The median numbers of baseline NRTI, thymidine analog mutations (TAM), PI and total mutations OSI-027 were 3, 3, 2 and 4.5, respectively (both primary and secondary mutations were included in the analysis for the PI mutations). After 12 weeks on study, 51 (55%) subjects had viral loads suppressed below 400 copies/ml. The number of subjects with viral suppression decreased to 31 (34%) and 29 (32%) at weeks 24 and 48, respectively. The association between the presence of a specific baseline mutation and virologic failure after 12 weeks of HAART was analyzed (Table ?(Table1).1). There was the suggestion of a OSI-027 potential association with virologic failure for only one baseline mutation, the NRTI codon 215 (unadjusted P = 0.019) for the three-drug combination regimen. However, in this case the presence of resistance mutations was associated with a decreased (rather than an increased) rate of viral failure at week 12. Table 1 Association of baseline NTRI resistance mutations and viral failure after 12 weeks on HAART thead d4T plus RTV group br / Number with a mutationZDV plus 3TC plus RTV group br / Number with a mutation hr / Baseline resistance mutation codonsRNA 400 at week 12 br OSI-027 / (N = 19)RNA 400 at week 12 br / (N = 26)RNA 400 at week 12 br / (N = 22)RNA 400 at week.