ABSTRACT: Objective: To determine the frequency of mutations associated with resistance to antiretroviral drugs in 400 therapy-naïve HIV-1-infected patients.
Patients and Methods: Three hundred and twenty seven therapy-naïve patients (253 male and 74 female) from 23 AIDS care centres in France were included in the study. In order to get representative estimates of the mutation frequencies, analysis was performed using the number of patients followed in the centres as a means of weighting the study. According to the CDC classification 80.1%, 10.5% and 9.4% were in stages A, B and C, respectively. The delay between seropositivity and inclusion in the study was more than 1 year in 249 patients (76%) [median 5.3 years; interquartile range (IQR) 1.1-808] and less than 1 year in 78 patients (24%). Population-based sequencing of the reverse transcriptase gene of plasma viruses was performed in the 327 patients. Sequencing of the protease gene was performed only in the specimens where mutations associated with reverse transcriptase inhibitor resistance were found.
Results: At inclusion, median CD4 cell counts and plasma HIV-1 RNA were 417 cells/mm3 (IQR: 237-587) and 22775 copies/ml (IQR: 6210-90994) respectively. Plasma viral load was below the detection limit in 4% of the 327 analyzed specimens. Nucleoside reverse transcriptase inhibitor key mutations were observed at codons 184 (one patient), 151 (one patient) and 215 (four patients) with a weighted prevalence of 1.1% (95% CI: 0-2.3). The weighted frequency of minor nucleoside reverse transcriptase inhibitor substitutions was 3.7% (95 CI: 1.6-5.7%). Weighted prevalences of major (Y181C: one patient, K101E: two patients) and minor (V108I: three patients) mutations associated with non-nucleoside reverse transcriptase inhibitor resistance were 0.5% (95% CI: 0-1.3%) and 0.8% (95% CI: 0-1.8%) respectively. The weighted frequency of major reverse transcriptase mutations was higher in patients with seropositivity of less than 1 year. This difference was statistically significant (P=0.03). Protease gene analyses will be presented.
Conclusion: In this study there was a low frequency of mutations associated with resistance to reverse transcriptase inhibitors. Most patients harboring mutations had been infected for less than 1 year. Taken together these results indicate that, in France, genotyping, prior to treatment, is not necessary when patients have been infected for more than 1 year. In contrast it might be important in recently infected patients (<1 year).
