title: Rapid development of antiretroviral drug resistance mutations in HIV-infected children less than two years of age initiating protease inhibitor-based therapy in South Africa.
abstract: Data on the development of antiretroviral drug resistance in HIV-1-infected children receiving protease inhibitor (PI)-based antiretroviral therapy (ART) are limited. We examined antiretroviral resistance among a cohort of 323 South African HIV-infected children <2 years old exposed to nevirapine for prevention of mother-to-child transmission. Ritonavir (RTV) was used initially for 138 children who were <6 months old or receiving antimycobacterial therapy; otherwise children received lopinavir/ritonavir (LPV/r)-based ART. HIV-1 population sequencing of the pol gene was conducted on all pretreatment samples and on posttreatment samples for children who did not achieve HIV-1 plasma RNA <400 copies/ml by 52 weeks. Among children in the cohort, 38 died, 22 had <24 weeks follow-up, 209 achieved virologic suppression, and 54 did not. Of 41 children without virologic suppression with posttreatment HIV genotype data available, major resistance mutations were found in 32 (78%): 14 (36%) had PI mutations including V82A, M46I, and L90M; 29 (71%) had M184V/I; and three had NNRTI mutations (K103N, Y181C, and G190A). Among the children who did not achieve virologic suppression, none of the seven children treated exclusively with LPV/r developed PI-related mutations, compared with 14 of 32 (44%) who received RTV-based regimens (p=0.036); PI genotypes were unavailable for two children. Seventy-eight percent of children without virologic suppression developed resistance mutations that impact second-line ART options. Only children who received RTV-based ART developed major PI-related resistance mutations, and use of this regimen should be avoided.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Texas Health Sciences Center at San Antonio, USA.
authors.forename: Barbara S
authors.initials: BS
authors.lastname: Taylor
authors.forename: Gillian
authors.initials: G
authors.lastname: Hunt
authors.forename: Elaine J
authors.initials: EJ
authors.lastname: Abrams
authors.forename: Ashraf
authors.initials: A
authors.lastname: Coovadia
authors.forename: Tammy
authors.initials: T
authors.lastname: Meyers
authors.forename: Gayle
authors.initials: G
authors.lastname: Sherman
authors.forename: Renate
authors.initials: R
authors.lastname: Strehlau
authors.forename: Lynn
authors.initials: L
authors.lastname: Morris
authors.forename: Louise
authors.initials: L
authors.lastname: Kuhn
mesh_terms: D019943:Amino Acid Substitution; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D015331:Cohort Studies; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D016333:HIV Protease / Q000235:genetics*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D015497:HIV-1 / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D007223:Infant; D061466:Lopinavir / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D020125:Mutation, Missense; D019829:Nevirapine / Q000008:administration & dosage / Q000494:pharmacology; D012367:RNA, Viral / Q000097:blood; D019438:Ritonavir / Q000008:administration & dosage / Q000494:pharmacology; D017422:Sequence Analysis, DNA; D013019:South Africa; D019562:Viral Load; D054302:pol Gene Products, Human Immunodeficiency Virus / Q000235:genetics
chemical_list: D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D054302:pol Gene Products, Human Immunodeficiency Virus; D061466:Lopinavir; D019829:Nevirapine; D016333:HIV Protease; D019438:Ritonavir