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D. Richman: On comments by M.J. Field
Res. Virol. 1992, 143, 223
(~) INSTITUTPASTEUR/ELsEVIER Paris 1992
LETTERS TO THE EDITOR
COMMENTS ARISING FROM THE "DISCUSSION" OF THE 4TH FORUM IN VIROLOGY, "CLINICAL SIGNIFICANCE OF DRUG-RESISTANTVIRUSES" (REs, VIROL,, 1992, 143, 2)
E Brun-Vezinet and H. Fleury:
D. Richman:
On comments by S. Safrin
On comments by M.J. Field
AZT-resistant HIV1 isolates in AZT-naive patients have only been reported by groups (Morhi et al., Sixth International Conference on AIDS, San Francisco, 1990) using assays incorporating zidovudine into the primary isolation tissue culture medium for peripheral blood mononuclear cell (PBMC) co-culture. In such assays, the co-cultivated PBMC containing virus integrated into cellular DNA may yield infectious virus, even AZT-sensitive virus, which could be detected in the supernatants during the onemonth culture. This "primary resistance" has never been described when sensitivity assays were performed after conventional isolation of HIV1 from patients' PBMC by co-culture with the MT2 cell line or with PBMC from seronegative donors.
Whether AZT therapy selects for rare preexisting subpopulations of virus or whether the mutations emerge during prolonged therapy, is an issue that no one has yet been able to resolve experimentally. Nevertheless, the absence of any of the described resistance mutations in sequences obtained prior to therapy and the kinetics of the appearance of mutations over prolonged periods (Boucher et al., Larder et al., Mayers et al., Richman et al., see 4th Forum, Res. Virol., 1992, 143, 2) would appear to make the latter possibility more likely.
(~) INSTITUTPASTEUR/ELsEVIER Paris 1992
LETTERS TO THE EDITOR
COMMENTS ARISING FROM THE "DISCUSSION" OF THE 4TH FORUM IN VIROLOGY, "CLINICAL SIGNIFICANCE OF DRUG-RESISTANTVIRUSES" (REs, VIROL,, 1992, 143, 2)
E Brun-Vezinet and H. Fleury:
D. Richman:
On comments by S. Safrin
On comments by M.J. Field
AZT-resistant HIV1 isolates in AZT-naive patients have only been reported by groups (Morhi et al., Sixth International Conference on AIDS, San Francisco, 1990) using assays incorporating zidovudine into the primary isolation tissue culture medium for peripheral blood mononuclear cell (PBMC) co-culture. In such assays, the co-cultivated PBMC containing virus integrated into cellular DNA may yield infectious virus, even AZT-sensitive virus, which could be detected in the supernatants during the onemonth culture. This "primary resistance" has never been described when sensitivity assays were performed after conventional isolation of HIV1 from patients' PBMC by co-culture with the MT2 cell line or with PBMC from seronegative donors.
Whether AZT therapy selects for rare preexisting subpopulations of virus or whether the mutations emerge during prolonged therapy, is an issue that no one has yet been able to resolve experimentally. Nevertheless, the absence of any of the described resistance mutations in sequences obtained prior to therapy and the kinetics of the appearance of mutations over prolonged periods (Boucher et al., Larder et al., Mayers et al., Richman et al., see 4th Forum, Res. Virol., 1992, 143, 2) would appear to make the latter possibility more likely.