Predicted susceptibility of etravirine in HIV patients experiencing virological failure secondary to non-nucleoside reverse transcriptase inhibitor resistance in Argentina

Abstract

Introduction: Virological response to etravirine (ETR) is dependent on the type and number of non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance-associated mutations (RAMs).

Methods: Data on NNRTI used in HAART at the time of failure and the number of NNRTI-RAMs were collected and retrospectively analyzed. ETR-RAMs were defined as V90I, A98G, L100I, K101E/H/P, V106I, E138A, V179D/F/T, Y181C/I/V, G190A/S, and M230L, and were analyzed according to the weighted mutation score to predict susceptibility (Vingerhoets 2008).

Results: N=150. Efavirenz (EFV) containing regimen: 76.7%; nevirapine (NVP): 23.3%. Frequency of ETR-RAMs acquired after NNRTI failure: zero=38.7%, one=39.3%, two=17.3%, three=3.3%, four=1.3%. Most frequent ETR-RAMs after failure with EFV: G190A (28.1%), K101E (14.9%), L100I (10.5%); and with NVP: Y181C (41.7%), G190A (30.6%) and A98G (13.9%). Global predicted susceptibility of ETR: highest response: 69.3%, intermediate response: 24.7%, reduced response: 6%. Comparing maximal response with duration of virological failure: EFV-containing regimen: 94.4% (< 24-weeks) vs. 69.8% (>24-weeks) (p=0.02); NVP-containing regimen: 42.9% (< 24-weeks) vs. 56.5% (>24-weeks) (p=0.41). The presence of lamivudine regimen was associated with a better predicted susceptibility (highest response) to ETR (79% vs. 25%; P=.001).

Discussion: The majority of patients maintained susceptibility to ETR after the acquisition of NNRTI resistance. Failing with an EFV-containing regimen had a better predicted susceptibility to ETR than with NVP, especially after short-term virological failure.