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 development of mutation at codon 215 of HIV-1 reverse transcriptase and to identify baseline characteristics associated with this mutation following initiation of zidovudine therapy. To achieve such a purpose, 80 HIV-1-infected patients starting zidovudine therapy have been submitted to clinical, immunological and virological monitoring at entry and every 12 weeks. The critical end point of the study was time to development of mutation at codon 215. The association of key baseline characteristics (CD4(+) counts, clinical stage, HIV-1 p24 antigen, CD8(+) counts, serum beta(2)-microglobulin and virus phenotype) with the mutation at codon 315 was also investigated. A total of 38 subjects (48%) developed mutation at codon 215 during follow-up. The estimated Kaplan-Meier probability of remaining with wild genotype at 24, 48 and 96 weeks (96% CI) was 0.82 (0.73-0.90), 0.70 (0.60-0.80) and 0.53 (0.41-0.66) respectively. Univariate analysis showed that time to the development of mutation at codon 215 was positively associated with baseline p24 positivity, C clinical stage, low CD4(+) count and high beta(2)-microglobulin level. Only p24 antigenaemia and CD4(+) count remained significantly independent predictive factors for the development of mutation at codon 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 codon 215 was observed and HIV-1 p24 antigenaemia should be considered an independent predictor for faster development of zidovudine resistance.