Comparison of genotypic resistance profiles and virological response between patients starting nevirapine and efavirenz in EuroSIDA.
OBJECTIVE
To compare virological outcome and genotypic resistance profiles in HIV-1-infected patients starting non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing regimens.


METHODS
NNRTI-naive patients were included who started treatment with nevirapine (NVP) or efavirenz (EFV) with genotypic resistance test results available at time of initiation (baseline). Virological failure was defined as two consecutive values > 500 copies/ml after starting the regimen. Cox models were used to investigate time to virological failure (the first of two values).


RESULTS
A total of 759 patients were included (13% antiretroviral-naive): 389 initiated NVP and 370 initiated EFV. Baseline IAS-USA NNRTI resistance mutations were detected in 3%. Using the Rega algorithm (version 7.1) to interpret resistance, 460 (64%) patients had resistance (full or intermediate) to at least one drug they were starting (69% NVP, 60% EFV, P = 0.011); 287 (74%) NVP and 168 (45%) EFV patients experienced virological failure after treatment initiation, P < 0.001. After adjustment for previous antiretroviral use, previous AIDS, year started NNRTI, CD4 cell count (baseline, nadir), viral load (baseline, maximum), and baseline drug resistance (measured by Rega), the relative hazards (EFV versus NVP) of virological failure was 0.50, 95% confidence interval: 0.39-0.65, P < 0.001. At time of virological failure, comparable levels of NNRTI resistance were detected. The K103N mutation emerged more in patients failing EFV and Y181C in patients failing NVP.


CONCLUSIONS
NVP may be associated with an inferior virological outcome compared to EFV in NNRTI-naive patients with extensive resistance to other drug classes. The profile of NNRTI resistance mutations when virologically failing an NNRTI-containing regimen appears to depend on the NNRTI the patients fail.
Bannister
Wendy P
WP
Department of Primary Care and Population Sciences, Royal Free and University College Medical School, London, UK. w.bannister@pcps.ucl.ac.uk
Ruiz
Lidia
L
Cozzi-Lepri
Alessandro
A
Mocroft
Amanda
A
Kirk
Ole
O
Staszewski
Schlomo
S
Loveday
Clive
C
Karlsson
Anders
A
Monforte
Antonella d'Arminio
Ad
Clotet
Bonaventura
B
Lundgren
Jens D
JD
D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D048588:Benzoxazines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D015331:Cohort Studies; D003521:Cyclopropanes; D024882:Drug Resistance, Viral / Q000235:genetics*; D005060:Europe; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests / Q000379:methods; D008875:Middle Aged; D009154:Mutation; D019829:Nevirapine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D016016:Proportional Hazards Models; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D017211:Treatment Failure; D016896:Treatment Outcome
D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine; C098320:efavirenz