HIV-1 Protease Inhibitors Resistance Profiles in Patients with Virological Failure on LPV/r-based 2nd Line Regimen in Cambodia

Abstract

Objective: To describe the ARV resistance profiles of patients experiencing virological failure after at least 6 months on LPV/r-based 2nd line regimen in Cambodia. Design: Retrospective analysis of resistance testing of 89 patients with detectable viral load under LPV/r-based 2nd line regimen. Methods: Bulk sequencing of HIV-1 protease, reverse transcriptase and integrase PCR products. Results: Protease gene amplification was successful for 71/89 patients (80%). All were infected by CRF01_AE viruses. Among them, 42 did not present any resistance to PIs. A high level of resistance to PIs was observed for the 29 remaining patients. Twenty-six were resistant to LPV/r (8 possibly resistant). Twenty-eight, 21 and 20 were also found resistant to IDV, ATV/r and FPV/r, respectively. Twenty-six were resistant to NFV (11 possibly) and 22 to SQV/r (9 possibly). Finally, 22/29 (75.8%) were resistant to at least 3 PIs. Interestingly, 78.6% (22/29) were found sensitive to DRV/r. In this group, a high frequency of resistance to RTIs including ETV was also reported. No resistance to raltegravir (RAL) or elvitegravir (EVG) was observed (n=24). Detailed ARV histories documented for 15 patients revealed past exposition to multiple RTIs and PIs. Conclusion: Almost 2/3 of patients (60/89) with virological failure on LPV/r-based 2nd line in our study were not in urgent need for treatment change. In contrast, switching treatment was clearly required for 1/3 (29/89) presenting high level of resistance to PIs and RTIs. For those patients, DRV, RAL/EVG, and potentially ETV, could be good candidates for 3rd line ARV regimen if available.