The normalized inhibitory quotient of boosted protease inhibitors is predictive of viral load response in treatment-experienced HIV-1-infected individuals.
OBJECTIVE
The normalized inhibitory quotient (NIQ) has been proposed as a measure for refining the precision of HIV resistance testing when selecting antiretroviral therapy (ART). We undertook an assessment of NIQ and 48-week virological outcome in patients commencing ritonavir-boosted protease inhibitor (PI) regimens.


METHODS
A cohort of 87 HIV-infected individuals who all had extensive prior exposure to ART were assigned a new boosted PI regimen following resistance testing. PI therapy consisted of lopinavir, indinavir, saquinavir and amprenavir at 50, 32, 11 and 6%, respectively. Fold change (FC) for each PI was determined from the resistance test at baseline. Trough drug concentration (Cmin) was determined at week 4.


METHODS
NIQ was derived individually by taking the logarithm of the ratio of Cmin/FC divided by the fixed ratio of population mean trough drug concentration/clinical cut off. Associations between viral load (VL) response over 48 weeks with baseline VL, FC, Cmin, NIQ and selected PI were assessed.


RESULTS
Mean change from baseline VL reduced by 0.83 log at week 48. In multivariate analyses, baseline VL and NIQ were the parameters most associated with change from baseline VL at week 48 (P = 0.012 and 0.003, respectively). FC, Cmin and selected PI were not significantly associated with VL changes.


CONCLUSIONS
In this cohort of highly treatment-experienced individuals treated with boosted PI regimens, baseline VL and NIQ were significantly predictive of virological response over 48 weeks whereas FC and Cmin were not. These results support the use of a NIQ at week 4, as a tool for predicting response to therapy in this setting.
Winston
Alan
A
National Centre for HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, NSW 2010, Australia. alan_winston71@yahoo.com
Hales
Gill
G
Amin
Janaki
J
van Schaick
Erno
E
Cooper
David A
DA
Emery
Sean
S
D023241:Antiretroviral Therapy, Highly Active; D024882:Drug Resistance, Viral / Q000235:genetics; D005500:Follow-Up Studies; D005838:Genotype; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000097:blood / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D010641:Phenotype; D011379:Prognosis; D012367:RNA, Viral / Q000097:blood; D019438:Ritonavir / Q000097:blood / Q000627:therapeutic use; D016879:Salvage Therapy / Q000379:methods; D016896:Treatment Outcome; D019562:Viral Load
D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D019438:Ritonavir