J Med Virol. 1997 Jan;51(1):48-55. Unique Identifier : AIDSLINE
Sequential isolates from four patients under zidovudine (ZDV) therapy
were obtained using PBMC coculture in the absence or in the presence of
0.25 microM ZDV. PBMC-based HIV susceptibility assay demonstrated the
emergence of ZDV-resistance in the sequential isolates from the four
patients. Except in one case, the isolates obtained in the presence of
ZDV did not exhibit a greater resistance pattern than their counterparts
obtained in the absence of the drug. In parallel, partial reverse
transcriptase gene sequence was determined directly on amplified
products from proviral DNA. In addition to the mutations previously
described at the critical codons 41, 67, 70, 215, and 219, numerous
additional mutations were found in either ZDV-sensitive or ZDV-resistant
isolates. The mutation Thr215Tyr was not observed in a case of highly
resistant virus (ZDV IC50 > 6.25 microM), while the mutation Lys70Arg
was found in either resistant or sensitive ones. The analysis of
additional mutations did not reveal any clear pattern for ZDV resistance
but pointed out the existence of highly variable regions neighbouring
the five critical codons. Neither nucleotide sequence nor PBMC-based
susceptibility assay provided unambiguous data about pretherapy isolates
or early on-therapy isolates which could predict the emergence of ZDV
resistance in further samples.
*Anti-HIV Agents/THERAPEUTIC USE *HIV Infections/DRUG THERAPY *HIV
Infections/GENETICS *HIV-1/DRUG EFFECTS *HIV-1/GENETICS
*Mutagenesis/DRUG EFFECTS *Zidovudine/THERAPEUTIC USE