Abstract
Human immunodeficiency virus type 1 (HIV-1) isolates resistant to zidovudine (ZDV) have previously been demonstrated to exhibit in vitro cross- resistance to other similar dideoxynucleoside agents which contain a 3'- azido group. However, cross-resistance to didanosine (ddI) or dideoxycytidine (ddC) has been less well documented. ZDV, ddI, and ddC susceptibility data have been collected from clinical HIV-1 isolates obtained by five clinical centers and their respective retrovirology laboratories. All subjects were treated only with ZDV. Clinical HIV-1 isolates were isolated, amplified, and assayed for drug susceptibility in standardized cultures of phytohemagglutinin-stimulated donor peripheral blood mononuclear cells obtained from healthy seronegative donors. All five cohorts showed a correlation between decreased in vitro susceptibility to ZDV and decreased susceptibility to ddI and ddC. For each 10-fold decrease in ZDV susceptibility, an average corresponding decrease of 2.2-fold in ddI susceptibility was observed (129 isolates studied; P < 0.001, Fisher's test of combined significance). Similarly, susceptibility to ddC decreased 2.0- fold for each 10-fold decrease in ZDV susceptibility (82 isolates studied; P < 0.001, Fisher's test of combined significance). These data indicate that a correlation exists between HIV-1 susceptibilities to ZDV and ddI or ddC for clinical HIV-1 isolates.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 307-314 |
| Number of pages | 8 |
| Journal | Antimicrobial Agents and Chemotherapy |
| Volume | 38 |
| Issue number | 2 |
| State | Published - 1994 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Pharmacology (medical)
Cite this
Dideoxynucleoside resistance emerges with prolonged zidovudine monotherapy. / Mayers, D. L.; Japour, A. J.; Arduino, J. M.; Hammer, S. M.; Reichman, R.; Wagner, K. F.; Chung, R.; Lane, J.; Crumpacker, C. S.; McLeod, G. X.; Beckett, Laurel A; Roberts, C. R.; Winslow, D.; Burke, D.; Ruiz, N.; Fujimara-Justice, M.; Kernozek, P.; Koch, J.; Brewer, C.
In: Antimicrobial Agents and Chemotherapy, Vol. 38, No. 2, 1994, p. 307-314.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Dideoxynucleoside resistance emerges with prolonged zidovudine monotherapy
AU - Mayers, D. L.
AU - Japour, A. J.
AU - Arduino, J. M.
AU - Hammer, S. M.
AU - Reichman, R.
AU - Wagner, K. F.
AU - Chung, R.
AU - Lane, J.
AU - Crumpacker, C. S.
AU - McLeod, G. X.
AU - Beckett, Laurel A
AU - Roberts, C. R.
AU - Winslow, D.
AU - Burke, D.
AU - Ruiz, N.
AU - Fujimara-Justice, M.
AU - Kernozek, P.
AU - Koch, J.
AU - Brewer, C.
PY - 1994
Y1 - 1994
N2 - Human immunodeficiency virus type 1 (HIV-1) isolates resistant to zidovudine (ZDV) have previously been demonstrated to exhibit in vitro cross- resistance to other similar dideoxynucleoside agents which contain a 3'- azido group. However, cross-resistance to didanosine (ddI) or dideoxycytidine (ddC) has been less well documented. ZDV, ddI, and ddC susceptibility data have been collected from clinical HIV-1 isolates obtained by five clinical centers and their respective retrovirology laboratories. All subjects were treated only with ZDV. Clinical HIV-1 isolates were isolated, amplified, and assayed for drug susceptibility in standardized cultures of phytohemagglutinin-stimulated donor peripheral blood mononuclear cells obtained from healthy seronegative donors. All five cohorts showed a correlation between decreased in vitro susceptibility to ZDV and decreased susceptibility to ddI and ddC. For each 10-fold decrease in ZDV susceptibility, an average corresponding decrease of 2.2-fold in ddI susceptibility was observed (129 isolates studied; P < 0.001, Fisher's test of combined significance). Similarly, susceptibility to ddC decreased 2.0- fold for each 10-fold decrease in ZDV susceptibility (82 isolates studied; P < 0.001, Fisher's test of combined significance). These data indicate that a correlation exists between HIV-1 susceptibilities to ZDV and ddI or ddC for clinical HIV-1 isolates.
AB - Human immunodeficiency virus type 1 (HIV-1) isolates resistant to zidovudine (ZDV) have previously been demonstrated to exhibit in vitro cross- resistance to other similar dideoxynucleoside agents which contain a 3'- azido group. However, cross-resistance to didanosine (ddI) or dideoxycytidine (ddC) has been less well documented. ZDV, ddI, and ddC susceptibility data have been collected from clinical HIV-1 isolates obtained by five clinical centers and their respective retrovirology laboratories. All subjects were treated only with ZDV. Clinical HIV-1 isolates were isolated, amplified, and assayed for drug susceptibility in standardized cultures of phytohemagglutinin-stimulated donor peripheral blood mononuclear cells obtained from healthy seronegative donors. All five cohorts showed a correlation between decreased in vitro susceptibility to ZDV and decreased susceptibility to ddI and ddC. For each 10-fold decrease in ZDV susceptibility, an average corresponding decrease of 2.2-fold in ddI susceptibility was observed (129 isolates studied; P < 0.001, Fisher's test of combined significance). Similarly, susceptibility to ddC decreased 2.0- fold for each 10-fold decrease in ZDV susceptibility (82 isolates studied; P < 0.001, Fisher's test of combined significance). These data indicate that a correlation exists between HIV-1 susceptibilities to ZDV and ddI or ddC for clinical HIV-1 isolates.
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M3 - Article
VL - 38
SP - 307
EP - 314
JO - Antimicrobial Agents and Chemotherapy
JF - Antimicrobial Agents and Chemotherapy
SN - 0066-4804
IS - 2
ER -