Non-nucleoside reverse transcriptase inhibitor resistance among patients failing a nevirapine plus protease inhibitor-containing regimen.

Objective: To determine the rate of nevirapine resistance in patients failing a nevirapine plus protease inhibitor (PI)-based regimen, and whether these isolates remain susceptible to other non-nucleoside reverse transcriptase inhibitors (NNRT1). Design and setting: A retrospective cohort study in two tertiary university hospitals. Patients: Eighty-eight HIV-infected, NNRTI-naive patients receiving nevirapine plus PI as a rescue regimen after PI treatment failure. Main outcome measures: Genotypic and phenotypic resistance data at inclusion (73 and 60 plasma samples, respectively) and after 24 weeks (53 and 42 samples). Results: Baseline phenotypic susceptibility to nevirapine was found in 70% of patients, and similar data were observed for efavirenz (91%) and delavirdine (71%). NNRTI resistance-associated mutations were found in 11 patients (12.5%). At 24 weeks, resistant isolates to nevirapine were found in 92% of patients, and correlated with similar resistance to efavirenz (68%) and delavirdine (73%). In the genotypic analysis, the Y181C mutation was observed in 76% of mutants, and the most common changes were a combination of mutations at positions Y181C/K103N (23%) and the single mutation Y181C (15%). The development of nevirapine resistance was associated with baseline resistance to PI included in the regimen (P = 0.01). For isolates containing the single amino acid substitution Y181C, 29% remained fully susceptible to efavirenz, whereas 14% showed intermediate resistance to efavirenz and delavirdine. Conclusion: The failure of a nevirapine plus PI-containing regimen is associated with nevirapine resistance in most patients, with the most common mutation occurring at amino acid residue 181. Although there is a high degree of cross-resistance among NNRTI, nearly one third of resistant isolates carrying the single Y181C mutation remain susceptible to efavirenz.