DEVELOPMENT OF LYS TO ARG MUTATION AT CODON-70 OF THE REVERSE-TRANSCRIPTASE GENE OF HIV-1 DURING ZIDOVUDINE MONOTHERAPY AND ALTERNATING ZIDOVUDINE DIDANOSINE THERAPY/
L. Bruun et al., DEVELOPMENT OF LYS TO ARG MUTATION AT CODON-70 OF THE REVERSE-TRANSCRIPTASE GENE OF HIV-1 DURING ZIDOVUDINE MONOTHERAPY AND ALTERNATING ZIDOVUDINE DIDANOSINE THERAPY/, Antiviral therapy, 3(2), 1998, pp. 89-95
Objective: To study the association between the Lys to Arg mutation at
codon 70 of the reverse transcriptase (RT) gene and resistance develo
pment during zidovudine monotherapy and alternating zidovudine/didanos
ine therapy. Methods: Blood samples from 33 antiretroviral-naive patie
nts were drawn prior to therapy and after 6, 12, 18 and 24 months (18
patients received zidovudine monotherapy and 15 patients alternating z
idovudine/didanosine). Results: After 6 months of zidovudine monothera
py, 72% of the patients had provirus encoding Lys to Arg at codon 70.
This decreased to 53% and 38% after 12 and 18 months, respectively, bu
t increased to 60% after 24 months. During alternating zidovudine/dida
nosine therapy, the percentages with the mutation were 6%, 7%, 11% and
20% after 6, 12, 18 and 24 months of therapy, respectively. During bo
th therapy regimens provirus showed the same progression of mutations
in RT codons 41 and 215, increasing from 10% after 6 months to 80-100%
after 24 months. Codon 70 and 215 mutations together were only found
with the codon 67 mutation. No significant difference in IC50 or viral
load was shown between patients on either therapy. Conclusions: The c
odon 70 mutation was present in a low proportion of the patients durin
g alternating zidovudine/didanosine therapy compared with patients on
zidovudine monotherapy (P<0.01). Mutations associated with zidovudine
resistance appeared in an ordered manner. Based on the phenotypic susc
eptibility of the virus isolated, the appearance of the different comb
inations of mutations could be explained by outgrowth of virus with an
increased level of phenotypic resistance.