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 (NNRTI).


METHODS
A retrospective cohort study in two tertiary university hospitals.


METHODS
Eighty-eight HIV-infected, NNRTI-naive patients receiving nevirapine plus PI as a rescue regimen after PI treatment failure.


METHODS
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 Y181 C 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.


CONCLUSIONS
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.
Casado
J L
JL
Infectious Diseases Unit, Ramon y Cajal Hospital, Madrid, Spain. jcasado@hrc.insalud.es
Hertogs
K
K
Ruiz
L
L
Dronda
F
F
Van Cauwenberge
A
A
Arnó
A
A
Garcia-Arata
I
I
Bloor
S
S
Bonjoch
A
A
Blazquez
J
J
Clotet
B
B
Larder
B
B
D000328:Adult; D000480:Alkynes; D048588:Benzoxazines; D015331:Cohort Studies; D003521:Cyclopropanes; D020008:Delavirdine / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D018432:Drug Resistance, Multiple; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006785:Hospitals, University; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D019829:Nevirapine / Q000627:therapeutic use*; D010078:Oxazines / Q000494:pharmacology; D011480:Protease Inhibitors / Q000627:therapeutic use*; D012367:RNA, Viral / Q000032:analysis / Q000235:genetics; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D013997:Time Factors; D019562:Viral Load
D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D010078:Oxazines; D011480:Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine; D020008:Delavirdine; C098320:efavirenz