Analysis of Human Immunodeficiency Virus Type 1 Drug Resistance in Children Receiving Nucleoside Analogue Reverse-Transcriptase Inhibitors plus Nevirapine, Nelfinavir, or Ritonavir (Pediatric AIDS Clinical Trials Group 377)

• Published in: The Journal of infectious diseases 2001-06, Vol.183 (12), p.1732-1738
• Main Authors: Eshleman, Susan H., Krogstad, Paul, Jackson, J. Brooks, Wang, You-Gan, Lee, Sophia, Wei, Lee-Jen, Cunningham, Shawn, Wantman, Michael, Wiznia, Andrew, Johnson, George, Nachman, Sharon, Palumbo, Paul
• Format: Article
• Language: English
• Subjects: Adolescent; AIDS; Anti-HIV Agents - pharmacology; Anti-HIV Agents - therapeutic use; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiretroviral Therapy, Highly Active; Antiretrovirals; Antiviral agents; Biological and medical sciences; Child; Child health services; Child, Preschool; Cohort Studies; Drug resistance; Drug Resistance, Microbial - genetics; Female; Genetic mutation; Genotype; HIV 1; HIV Infections - drug therapy; HIV Infections - genetics; HIV Infections - virology; HIV-1 - drug effects; HIV-1 - genetics; Human immunodeficiency virus 1; Human viral diseases; Humans; Infant; Infectious diseases; Lamivudine - pharmacology; Lamivudine - therapeutic use; Major Articles; Male; Medical sciences; Mutation; nelfinavir; Nelfinavir - pharmacology; Nelfinavir - therapeutic use; nevirapine; Nevirapine - pharmacology; Nevirapine - therapeutic use; nucleoside analogues; Pediatrics; Pharmacology. Drug treatments; Reverse Transcriptase Inhibitors - pharmacology; Reverse Transcriptase Inhibitors - therapeutic use; Ritonavir - pharmacology; Ritonavir - therapeutic use; RNA; RNA, Viral - blood; stavudine; Stavudine - pharmacology; Stavudine - therapeutic use; Treatment Failure; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral Load; Virology; Viruses
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/320728

In Pediatric AIDS Clinical Trials Group 377, antiretroviral therapy–experienced children were randomized to 4 treatment arms that included different combinations of stavudine, lamivudine (3TC), nevirapine (Nvp), nelfinavir (Nfv), and ritonavir (Rtv). Previous treatment with zidovudine (Zdv), didanosine (ddI), or zalcitabine (ddC) was acceptable. Drug resistance (R) mutations were assessed before study treatment (baseline) and at virologic failure. ZdvR, ddIR, and ddCR mutations were detected frequently at baseline but were not associated with virologic failure. Children with drug resistance mutations at baseline had greater reductions in virus load over time than did children who did not. NvpR and 3TCR mutations were detected frequently at virologic failure, and NvpR mutations were more common among children receiving 3-drug versus 4-drug Nvp-containing regimens. Children who were maintained on their study regimen after virologic failure accumulated additional NvpR and 3TCR mutations plus RtvR and NfvR mutations. However, RtvR and NfvR mutations were detected at unexpectedly low rates