PREVALENCE AND CLINICAL-SIGNIFICANCE OF ZIDOVUDINE RESISTANCE MUTATIONS IN HUMAN-IMMUNODEFICIENCY-VIRUS ISOLATED FROM PATIENTS AFTER LONG-TERM ZIDOVUDINE TREATMENT

Zidovudine resistance mutations at reverse transcriptase codons 215 or 41 were found in two-thirds of human immunodeficiency virus type 1 (HIV-1) isolates obtained at baseline from patients enrolled in an AIDS Clinical Trials Group (ACTG) protocol that compared didanosine with continued zidovudine in patients with greater than or equal to 16 weeks of previous zidovudine therapy (ACTG 116B/117). The combined presence of mutations at both codons 215 and 41 conferred an increased risk for progression (relative hazard, 1.82; 95% confidence interval [CI], 1.02-3.26) and an increased risk for death (RH, 5.42; 95% CI, 1.92-15.30) in analyses that controlled for other factors predictive of progression. However, the benefit of switching to didanosine compared with continued zidovudine therapy was independent of the presence of these mutations. Although this information is not helpful in determining when to alter therapy, detection of zidovudine resistance mutations provides prognostic information in patients with advanced HIV disease.