REVERSE-TRANSCRIPTASE GENOTYPE AND ANTIRETROVIRAL SUSCEPTIBILITY OF HUMAN-IMMUNODEFICIENCY-VIRUS ISOLATES FROM PATIENTS WITH ADVANCED DISEASE TREATED WITH DIDANOSINE - CORRELATION WITH VIROLOGICAL RESPONSE ANDSURVIVAL

To identify correlates of virologic response and survival, the reverse transcriptase (Ri) genotype and in vitro antiviral susceptibility of human immunodeficiency virus (HIV) isolates from 20 patients treated W ith didanosine were studied. Patients had advanced HIV disease and wer e intolerant to or had failed zidovudine. Neither Ri genotype nor anti viral susceptibility testing, as determined by a peripheral blood mono nuclear cell-based assay, correlated with a virologic response to dida nosine, as determined previously by quantitative serum culture. Only o ne (8%) Of 12 isolates obtained after 6-12 months of treatment showed mutation at codon 74 conferring didanosine resistance. Reversions were seen iii three of five patients with pre-treatment zidovudine resista nce mutations at codons 70, but in none of eight with mutations at cod on 215. Pretreatment isolates encoding mutations at RT codon 215 or en coding codon 123 asp were associated with both significantly greater C D4 lymphocyte depletion and shorter survival. In this cohort of patien ts with advanced HIV disease, neither rapid emergence of didanosine re sistance nor rapid reversion of zidovudine resistance was observed. To better understand the relationship between virologic response and in vitro susceptibility to didanosine, more precise tools may be needed. (C) 1996 Wiley-Liss, Inc.