Viral resuppression and detection of drug resistance following interruption of a suppressive non-nucleoside reverse transcriptase inhibitor-based regimen.
BACKGROUND
Interruption of a non-nucleoside reverse transcriptase inhibitor (NNRTI)-regimen is often necessary, but must be performed with caution because NNRTIs have a low genetic barrier to resistance. Limited data exist to guide clinical practice on the best interruption strategy to use.


METHODS
Patients in the drug-conservation arm of the Strategies for Management of Antiretroviral Therapy (SMART) trial who interrupted a fully suppressive NNRTI-regimen were evaluated. From 2003, SMART recommended interruption of an NNRTI by a staggered interruption, in which the NNRTI was stopped before the NRTIs, or by replacing the NNRTI with another drug before interruption. Simultaneous interruption of all antiretrovirals was discouraged. Resuppression rates 4-8 months after reinitiating NNRTI-therapy were assessed, as was the detection of drug-resistance mutations within 2 months of the treatment interruption in a subset (N = 141).


RESULTS
Overall, 601/688 (87.4%) patients who restarted an NNRTI achieved viral resuppression. The adjusted odds ratio (95% confidence interval) for achieving resuppression was 1.94 (1.02-3.69) for patients with a staggered interruption and 3.64 (1.37-9.64) for those with a switched interruption compared with patients with a simultaneous interruption. At least one NNRTI-mutation was detected in the virus of 16.4% patients with simultaneous interruption, 12.5% patients with staggered interruption and 4.2% patients with switched interruption. Fewer patients with detectable mutations (i.e. 69.2%) achieved HIV-RNA of 400 copies/ml or less compared with those in whom no mutations were detected (i.e. 86.7%; P = 0.05).


CONCLUSIONS
In patients who interrupt a suppressive NNRTI-regimen, the choice of interruption strategy may influence resuppression rates when restarting a similar regimen. NNRTI drug-resistance mutations were observed in a relatively high proportion of patients. These data provide additional support for a staggered or switched interruption strategy for NNRTI drugs.
Fox
Zoe
Z
Copenhagen HIV Programme, University of Copenhagen/Rigshospitalet, Copenhagen, Denmark. z.fox@pcps.ucl.ac.uk
Phillips
Andrew
A
Cohen
Cal
C
Neuhaus
Jacquie
J
Baxter
John
J
Emery
Sean
S
Hirschel
Bernard
B
Hullsiek
Kathy Huppler
KH
Stephan
Christoph
C
Lundgren
Jens
J
D000328:Adult; D018791:CD4 Lymphocyte Count; D002985:Clinical Protocols; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral / Q000235:genetics / Q000276:immunology*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D017410:Practice Guidelines as Topic; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage* / Q000276:immunology; D016896:Treatment Outcome; D019562:Viral Load
D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase