title: Drug resistance mutations during structured interruptions of HAART in two HIV-1-infected children.
abstract: Information concerning structured treatment interruptions (STI) of the Highly Active Antiretroviral Therapy (HAART) and their risk for selecting antiretroviral drug resistance in children is scarce. In this study, we searched for antiretroviral drug resistance mutations at the end of five viral rebounds of two children with HIV and a chronically undetectable viral load (VL) who underwent an STI program. The HAART was interrupted for 4 weeks and then restarted and continued for 12 weeks for three cycles. VL, CD4+/CD8+ lymphocytes, and clinical status were evaluated at the end of each STI and at 6 and 12 weeks after HAART was resumed. Treatment of both the patients based on zidovudine+lamivudine+ritonavir remained identical during the study. The reverse transcriptase (RT)- and protease (PR)-coding regions were sequenced at the end of each viral rebound. One patient experienced progressively lower viral rebounds (269000-31300 at the first and third rebounds, respectively), while the other patient did not experience such a reduction, and the VL of both the patients fell to undetectable levels during therapy. In the five viral rebounds examined, no mutations for resistance to protease inhibitors (PIs) were found and the analysis indicated susceptibility to all PIs currently in clinical use. Although the mutation K103R associated with non-nucleoside reverse transcriptase inhibitor resistance was found in two viral rebounds of one patient, the analysis indicated the absence of resistance to RT inhibitors. As no mutation related to antiretroviral drug resistance was found, our results suggest that the STI program evaluated may have a low risk of selecting antiretroviral drug resistance. Nevertheless, further studies evaluating larger cohorts over longer periods are required before definitive conclusions about the safety of STI of HAART in children may be drawn.
authors: División de Investigación, Departamento de Pediatría and Infectología Pediátrica, Unidad Médica de Alta Especialidad, Hospital de Especialidades No. 25 and Centro de Investigación Biomédica del Noreste, Instituto Mexicano del Seguro Social, Monterrey, Nuevo León, México. palsaugc@gmail.com
authors: Gerardo C
authors: GC
authors: Palacios-Saucedo
authors: Lydia G
authors: LG
authors: Rivera-Morales
authors: José M
authors: JM
authors: Vázquez-Guillén
authors: Luz M
authors: LM
authors: Sánchez
authors: Teresa J
authors: TJ
authors: Ramírez
authors: Evangelina
authors: E
authors: Briones
authors: Rocío
authors: R
authors: Ortiz-López
authors: Carlos A
authors: CA
authors: Vázquez
authors: Cristina
authors: C
authors: Rodríguez-Padilla
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D016516:CD4-CD8 Ratio; D002648:Child; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000821:virology*; D016333:HIV Protease / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D017422:Sequence Analysis, DNA; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D016333:HIV Protease