Dideoxynucleoside Resistance Emerges With Prolonged Zidovudine Monotherapy

Mayers, DL, AJ Japour, JM Arduino, SM Hammer, R Reichman, KF Wagner, R Chung, J Lane, CS Crumpacker, GX Mcleod, LA Beckett, CR Roberts, D Winslow, D Burke, N Ruiz, M Fujimarajustice, P Kernozek, J Koch, C Brewer, C Hicks, ME Shellie, L Lorizlim, C Smalls, A Hamilton, F McCutchan, E Sandersbuell, O Weislow, A Fowler, J Lane and L Merritt

Antimicrob. Agents Chemother.. 1994. 38(2):307-314.

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.

Keywords: Metaanalysis; Mega-analysis; Technology Assessment; Fish Oil; Eicosapentaenoic Acid; Rheumatoid Arthritis, Polyunsaturated Fatty-acids; Acute Myocardial-infarction; Dietary Supplementation; Clinical-trials; Docosahexaenoic Acids; Generation; Publication; Quality, Alameda County; Health; Life; Predictors; Mortality; Cohort, Dementing Illnesses; Senile Dementia; United-states; Prevalence; Periods; Lundby; Rates, Placebo-controlled Trial; Hiv; Aids; azt, Urinary-incontinence; Prevalence; Symptoms; Questionnaire; Patterns, Human-immunodeficiency-virus; Hiv-1 Reverse-transcriptase; High-level Resistance; Reduced Sensitivity; Azt; Mutations; Therapy; Type-1; Susceptibility; Variants

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