A randomized controlled trial of genotypic HIV drug resistance testing in HIV-1-infected children: The PERA (PENTA 8) trial

Objective: To evaluate the longer-term utility of genotypic resistance testing in HIV-1-infected children with virological failure. Methods: Children aged 3 months-18 years switching antiretroviral therapy (ART) with HIV-1 RNA > 2,000 copies/ml were randomized between genotypic testing (Virtual Phenotype (TM)) and no testing at baseline and subsequent virological failures. Children were followed to at least 96 weeks. Results: One hundred and seventy eligible children, from 24 clinical centres in six countries, were randomized to resistance testing (n=87) or no testing (n=83) between June 2000-July 2003. At baseline, mean HIV-1 RNA and CD4(+) T-cell percentage were 4.7 log(10) copies/ml and 20%, respectively. Children had taken ART for a mean of 5 years; 24% had received all three classes, 53% nucleoside reverse transcriptase inhibitors (NRTIs)+protease inhibitors (PIs), 9% NRTIs+non-nucleoside reverse transcriptase inhibitors (NNRTIs) and 14% NRTIs only. There was no difference between the arms in the drug classes or the individual PIs/NNRTIs prescribed. However, 49% in the resistance test arm (RT) versus 19% in the no-test arm (NT) continued at least one NRTI from their failing regimen; 56% versus 19% were prescribed didanosine+stavudine as their NRTI backbone. Adjusting for baseline HIV-1 RNA, mean reductions in HIV-1 RNA at 48 weeks were 1.51 log(10) copies/ml in the RT arm and 1.23 in the NT arm (P=0.3); the difference between the arms was smaller at week 96 (RT: 1.50, NT: 1.47; P=0.9). Conclusion: In this first paediatric trial of resistance testing, we observed a substantial difference in NRTI-prescribing behaviour across arms. However statistically significant evidence of a long-term virological or immunological benefit was not observed. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN14367816.