Baseline human immunodeficiency virus type 1 phenotype, genotype, and RNA response after switching from long-term hard-capsule saquinavir to indinavir or soft-gel-capsule saquinavir in AIDS clinical trials group protocol 333.
AIDS Clinical Trials Group protocol 333 was an open-label trial of a switch from saquinavir (SQV) hard capsules (SQVhc) to indinavir (IDV) or saquinavir soft-gel capsules (SQVsgc) after >48 weeks of prior treatment with SQVhc. Eighty-nine subjects received IDV or SQVsgc or continued to receive SQVhc and continued unchanged treatment with non-protease-inhibitor antivirals for 8 weeks. Subjects receiving SQVhc then switched treatment to IDV. Baseline drug susceptibility and protease gene sequencing were done; 12 codons related to IDV and SQV resistance were analyzed. After 112 weeks (median) of SQVhc, the fall in human immunodeficiency virus (HIV) type 1 RNA level from baseline was significantly greater with IDV and was inversely correlated with the number of protease substitutions. The number of substitutions also correlated with baseline CD4 cell count, HIV-1 RNA level, SQV experience, and drug susceptibility. Substitution at codon 10, which occurred only in isolates with >/=2 substitutions, was associated with blunted RNA response. IDV IC(50) correlated with HIV-1 RNA response after the switch to IDV but added little predictive power once the genotype was considered.
Para
M F
MF
Ohio State University ACTU, University Hospitals Clinic, Columbus, OH 43210, USA. para.1@osu.edu
Glidden
D V
DV
Coombs
R W
RW
Collier
A C
AC
Condra
J H
JH
Craig
C
C
Bassett
R
R
Leavitt
R
R
Snyder
S
S
McAuliffe
V
V
Boucher
C
C
D000293:Adolescent; D000328:Adult; D002214:Capsules; D004334:Drug Administration Schedule; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics / Q000821:virology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D019469:Indinavir / Q000627:therapeutic use*; D008297:Male; D010641:Phenotype; D012367:RNA, Viral / Q000032:analysis*; D019258:Saquinavir / Q000008:administration & dosage / Q000627:therapeutic use*; D019562:Viral Load
D002214:Capsules; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D019469:Indinavir; D019258:Saquinavir