Resistance profiles and adherence at primary virological failure in three different highly active antiretroviral therapy regimens: analysis of failure rates in a randomized study.
OBJECTIVE
To investigate the interplay between resistance and adherence in the virological failure of three fundamentally different highly active antiretroviral therapy (HAART) regimens.


METHODS
We retrospectively identified 56 verified primary virological failures (viral load >400 HIV-1 RNA copies/mL) among 293 patients randomized to two nucleoside reverse transcriptase inhibitors (NRTIs)+ritonavir+saquinavir (RS-arm) (n=115), two NRTIs+nevirapine+nelfinavir (NN-arm) (n=118), or abacavir+stavudine+didanosine (ASD-arm) (n=60) followed up for a median of 90 weeks. Data on adherence were collected from patient files, and genotyping was performed on plasma samples collected at time of failure.


RESULTS
Treatment interruption or poor adherence was mainly caused by side effects and accounted for 74% of failures, and was associated with absence of resistance mutations. In the 30 failing patients not switched from randomized treatment, we found resistance in two of 12 patients in the RS-arm (M184 V only), four of six patients in the NN-arm [all four had non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations], and seven of 12 patients in the ASD-arm (NRTI mutations only). Two adherent patients on randomized treatment failed in the RS-arm, none in the NN-arm, and six in the ASD-arm.


CONCLUSIONS
Primary virological failure was caused mainly by treatment interruption. No primary protease inhibitor (PI) mutations were found in patients failing on boosted saquinavir, whereas resistance to NNRTIs and NRTIs was prevalent in several patients failing on regimens based on these medications.
Røge
B T
BT
Department of Infectious Diseases, Rigshospitalet, University Hospital of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
Barfod
T S
TS
Kirk
O
O
Katzenstein
T L
TL
Obel
N
N
Nielsen
H
H
Pedersen
C
C
Mathiesen
L R
LR
Lundgren
J D
JD
Gerstoft
J
J
D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008297:Male; D010349:Patient Compliance; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D017211:Treatment Failure; D019562:Viral Load
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors