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).
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 mutations were assessed before study treatment (baseline) and at virologic failure. Zdv, ddI, and ddC 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. Nvp and 3TC mutations were detected frequently at virologic failure, and Nvp 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 Nvp and 3TC mutations plus Rtv and Nfv mutations. However, Rtv and Nfv mutations were detected at unexpectedly low rates.
Eshleman
S H
SH
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21205, USA. seshlem@jhmi.edu
Krogstad
P
P
Jackson
J B
JB
Wang
Y G
YG
Lee
S
S
Wei
L J
LJ
Cunningham
S
S
Wantman
M
M
Wiznia
A
A
Johnson
G
G
Nachman
S
S
Palumbo
P
P
D000293:Adolescent; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004352:Drug Resistance, Microbial / Q000235:genetics; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007223:Infant; D019259:Lamivudine / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D009154:Mutation; D019888:Nelfinavir / Q000494:pharmacology / Q000627:therapeutic use; D019829:Nevirapine / Q000494:pharmacology / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D019438:Ritonavir / Q000494:pharmacology / Q000627:therapeutic use; D018119:Stavudine / Q000494:pharmacology / Q000627:therapeutic use; D017211:Treatment Failure; D019562:Viral Load
D019380:Anti-HIV Agents; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D019829:Nevirapine; D018119:Stavudine; D019888:Nelfinavir; D019438:Ritonavir