RATE OF DEVELOPMENT OF MUTATION AT CODON-215 OF HIV-1 REVERSE-TRANSCRIPTASE AND ITS PREDICTIVE FACTORS AT THE TIME OF INITIATION OF ZIDOVUDINE THERAPY

The objective of the present study was to determine the rate of develo pment of mutation at codon 215 of HIV-1 reverse transcriptase and to i dentify baseline characteristics associated with this mutation followi ng initiation of zidovudine therapy. To achieve such a purpose, 80 HIV -1-infected patients starting zidovudine therapy have been submitted t o clinical, immunological and virological monitoring at entry and ever y 12 weeks. The critical end point of the study was time to developmen t of mutation at codon 215. The association of key baseline characteri stics (CD4(+) counts, clinical stage, HIV-1 p24 antigen, CD8(+) counts , serum beta(2)-microglobulin and virus phenotype) with the mutation a t codon 315 was also investigated. A total of 38 subjects (48%) develo ped mutation at codon 215 during follow-up. The estimated Kaplan-Meier probability of remaining with wild genotype at 24, 48 and 96 weeks (9 6% CI) was 0.82 (0.73-0.90), 0.70 (0.60-0.80) and 0.53 (0.41-0.66) res pectively. Univariate analysis showed that time to the development of mutation at codon 215 was positively associated with baseline p24 posi tivity, C clinical stage, low CD4(+) count and high beta(2)-microglobu lin level. Only p24 antigenaemia and CD4(+) count remained significant ly independent predictive factors for the development of mutation at c odon 215 in the Cox proportional hazard stepwise regression analysis [ risk ratio (95% CI): 3.67 (1.75-7.70), P = 0.0007; 2.89 (1.17-6.72), P = 0.0073 respectively]. Thus, a continuous emergence of mutation at c odon 215 was observed and HIV-1 p24 antigenaemia should be considered an independent predictor for faster development of zidovudine resistan ce.