EVOLUTION OF HIV DRUG-RESISTANCE IN ZIDOVUDINE ZALCITABINE-EXPERIENCED AND ZIDOVUDINE/DIDANOSINE-EXPERIENCED PATIENTS RECEIVING LAMIVUDINE-CONTAINING COMBINATION THERAPY/
Jc. Schmit et al., EVOLUTION OF HIV DRUG-RESISTANCE IN ZIDOVUDINE ZALCITABINE-EXPERIENCED AND ZIDOVUDINE/DIDANOSINE-EXPERIENCED PATIENTS RECEIVING LAMIVUDINE-CONTAINING COMBINATION THERAPY/, Antiviral therapy, 3(2), 1998, pp. 81-88
Drug resistance patterns and their correlation to treatment response 2
4 weeks after addition of lamivudine to a previous zidovudine/zalcitab
ine or zidovudine/ didanosine combination treatment, or after substitu
tion of lamivudine for the zalcitabine or didanosine in these combinat
ions, were evaluated in 21 patients with CD4 counts between 50 and 300
cells/mm(3). immunological and virological outcomes were measured at
baseline and at weeks 4, 12 and 24. Drug resistance was assessed using
the recombinant virus assay and direct solid-phase sequencing of the
reverse transcriptase gene. Viral load decreased by an average of 0.78
log RNA copies/ml at week 4, but returned to baseline at week 24 for
most patients. CD4 cell counts increased in all treatment groups witho
ut reaching statistical significance. Resistance to lamivudine was rea
dily acquired in all four treatment groups and was often associated wi
th a partial reversal of phenotypic zidovudine resistance and a modera
te increase in the 50% inhibitory concentrations for didanosine and za
lcitabine. One patient receiving the zidovudine/didanosine combination
treatment harboured multi-nucleoside analogue-resistant virus. A poor
response to lamivudine tended to be related to the extent of pre-exis
ting zidovudine resistance.