ABSTRACT:
Complete suppression of HIV-1 could be compromised if a therapy-naïve patient already harbors virus resistant to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), or protease inhibitors (PIs). The frequency of resistance in newly infected patients has not been well characterized. Consequently, we analyzed plasma from 114 drug-naïve subjects, with documented infection within the last 3 years, for evidence of drug resistance. Genotyping was performed by direct sequencing of PCR products and resistance patterns were interpreted using the VircoGEN system.
A recombinant phenotypic assay (Antivirogram) was used for drug susceptibility determinations. Genotype (G) and phenotype (P) were obtained from 95 and 91 samples, respectively and defined as 'I' ('resistance possible' for G, 5-10-fold resistance for P), For NRTIs, the prevalence of resistance per individual was 1% (R) and 3% (I) for G, 1% (R) and 6% (I) for P. For NNRTIs the prevalence was 5% (R) and 10% (I) for G, 7.7% (R) and 15% (I) for P. For PIs the prevalence was 1% (R) and 8% (I) for G, 1% (R) and 0% (I) for P. The overall prevalence of any G-associated change or significant P change was 21%. Cases with at least one phenotypic R had significant genotypic polymorphisms in 100%, 100% and 50% for PIs, NRTIs and NNRTIs, respectively.
Cases with at least one phenotypic I had significant genotypic polymorphisms in 100%, 14% and 44% for PIs, NRTIs and NNRTIs, respectively. Significant genotype polymorphisms were seen in the absence of phenotypic resistance in eight, three and 10 cases for PI, NRTI and NNRTI, respectively. These anomalies could be due, in part, to an incomplete understanding of the genotypic correlates of resistance. The substantial prevalence of drug resistance found in this therapy-naïve cohort suggests that resistance testing prior to starting treatment could be useful in optimizing initial therapy.
