Resistance Costs and Future Drug Options of Antiretroviral Therapies: Analysis of the Role of NRTIs, NNRTIs, and PIs in a Large Clinical Cohort

Abstract

Objective To investigate future drug options (FDOs), resistance cost (RC_VF), and virologic response to genotypic-driven rescue highly active antiretroviral therapy (HAART), according to type of therapy. Method This was a retrospective analysis in naïve or antiretroviral-experienced patients. Virologic response was defined as HIV RNA <50 copies. Results There were 108 patients failing first-line HAART; there were 328 experienced patients. FDOs were reduced in subjects failing a thymidine-analogue (TA) regimen (median 3.65, IQR 1.29 ) compared to patients without TA (median 3.82, IQR 1.12) (p = .011). FDOs after first failure were higher for patients with non-nucleoside reverse transcriptase inhibitor (NNRTI; median 3.82; IQR 1.24) than with protease inhibitor (PI; median 3.64, IQR 1.15) (p = .027). In experienced patients, FDOs were much higher for TA (p = .005). Patients responding to genotypic-modified regimens had higher FDOs (median 3.9 4, IQR 2.53) than patients not responding (median 2.18, IQR 3.65) (p > .0001). Switching from an NNRTI-based HAART to a boosted PI had a higher chance (48.1%) of achieving a full virologic suppression, compared to switching from PI to NNRTI (21.4%, p < .0001). Conclusion FDOs and RC_VF are parameters that can quantify the therapeutic choices at virologic failure. Different drugs induce different FDOs and RC_VF. In successive-line regimens, the higher antiviral effect and genetic barrier of boosted PIs may overcome the limits of using nucleoside reverse transcriptase backbones, with only partial effectiveness.

Keywords:

• drug sequencing
• FDO
• first-line failure
• future drug option
• HAART
• resistance
• virologic failure