Genotypic and phenotypic resistance patterns at virological failure in a simplification trial with nevirapine, efavirenz or abacavir.
BACKGROUND
The NEFA Study was a randomized study comparing nevirapine (NVP), efavirenz (EFV) or abacavir (ABC) as substitutes for protease inhibitors in a large group of HIV-1-infected patients successfully treated with antiretroviral regimens containing protease inhibitors.


OBJECTIVE
To evaluate genotype and phenotype resistance patterns among patients who have experienced virological failure under one of the three study arms.


METHODS
Patients with virological failure, defined as two consecutive determinations of HIV-1 RNA > 200 copies/ml, were analysed for phenotypic susceptibility and HIV-1 mutations.


RESULTS
Of the 460 patients included in the study, 51 (11%) experienced virological failure after 24 months of follow-up while on assigned study medication. A higher proportion of patients in the ABC [25 (17%)] than in the NVP [14 (9%)] or EFV [12 (8%)] arms selected resistance to the study drug (P = 0.04). Moreover, a much higher number of resistance mutations to one or more of the backbone nucleoside reverse transcriptase inhibitor drugs contained in the failing regimen were observed in the ABC than in the EFV or NVP arms. In general, there was a good concordance among genotype and phenotype resistance testing, except for ABC, stavudine and didanosine, where phenotypic resistance testing added valuable information (fold change in the median inhibitory concentration).


CONCLUSIONS
Cross-resistance involving nucleoside reverse transcriptase inhibitor drugs might explain the higher risk of virological failure in patients switched to ABC-containing antiretroviral therapy. Phenotypic resistance testing may be helpful in interpreting unclear genotypic results.
Ochoa de Echagüen
Anna
A
Hospital Mutua de Terrassa, Terrassa, Spain.
Arnedo
Mireia
M
Xercavins
Mariona
M
Martinez
Esteban
E
Rosón
Beatriz
B
Ribera
Esteve
E
Domingo
Pere
P
González
Alicia
A
Riera
Melcior
M
Llibre
Josep Maria
JM
Gatell
Josep Maria
JM
Dalmau
David
D
D000328:Adult; D000368:Aged; D000480:Alkynes; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D048588:Benzoxazines; D003521:Cyclopropanes; D015224:Dideoxynucleosides / Q000494:pharmacology / Q000627:therapeutic use; D024882:Drug Resistance, Viral / Q000235:genetics*; D005500:Follow-Up Studies; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D019829:Nevirapine / Q000494:pharmacology / Q000627:therapeutic use; D010078:Oxazines / Q000494:pharmacology / Q000627:therapeutic use; D010641:Phenotype; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D017211:Treatment Failure; D000099227:Abacavir
D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D015224:Dideoxynucleosides; D019829:Nevirapine; D010078:Oxazines; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D000099227:Abacavir; C098320:efavirenz