Prevalence and clinical significance of zidovudine resistance mutations in human immunodeficiency virus isolated from patients after long-term zidovudine treatment. AIDS Clinical Trials Group 116B/117 Study Team and the Virology Committee Resistance Working Group.
Zidovudine resistance mutations at reverse transcriptase codons 215 or 41 were found in two-thirds of human immunodeficiency virus type 1 (HIV-1) isolates obtained at baseline from patients enrolled in an AIDS Clinical Trials Group (ACTG) protocol that compared didanosine with continued zidovudine in patients with > or = 16 weeks of previous zidovudine therapy (ACTG 116B/117). The combined presence of mutations at both codons 215 and 41 conferred an increased risk for progression (relative hazard, 1.82; 95% confidence interval [CI], 1.02-3.26) and an increased risk for death (RH, 5.42; 95% CI, 1.92-15.30) in analyses that controlled for other factors predictive of progression. However, the benefit of switching to didanosine compared with continued zidovudine therapy was independent of the presence of these mutations. Although this information is not helpful in determining when to alter therapy, detection of zidovudine resistance mutations provides prognostic information in patients with advanced HIV disease.
Japour
A J
AJ
Beth Israel Hospital, Boston, Massachusetts, USA.
Welles
S
S
D'Aquila
R T
RT
Johnson
V A
VA
Richman
D D
DD
Coombs
R W
RW
Reichelderfer
P S
PS
Kahn
J O
JO
Crumpacker
C S
CS
Kuritzkes
D R
DR
D000328:Adult; D002986:Clinical Trials as Topic; D003062:Codon / Q000235:genetics; D004279:DNA, Viral / Q000097:blood; D018450:Disease Progression; D004352:Drug Resistance, Microbial / Q000235:genetics; D005260:Female; D005819:Genetic Markers; D015658:HIV Infections / Q000188:drug therapy* / Q000401:mortality; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D012194:RNA-Directed DNA Polymerase / Q000235:genetics*; D012307:Risk Factors; D015215:Zidovudine / Q000627:therapeutic use*
D003062:Codon; D004279:DNA, Viral; D005819:Genetic Markers; D015215:Zidovudine; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase