AEGiS-Glasgow [PL6.6] The normalised inhibitory quotient of boosted protease inhibitors is predictive of viral load response over 48 weeks in a cohort of highly treatment experienced HIV-1 infected individuals

Seventh International Congress on Drug Therapy in HIV Infection

Glasgow, UK - 14-17 November 2004

[PL6.6] The normalised inhibitory quotient of boosted protease inhibitors is predictive of viral load response over 48 weeks in a cohort of highly treatment experienced HIV-1 infected individuals

Int Cong Drug Therapy HIV 2004 Nov 14-18;7:Abstract No. PL6.6

A. Winston¹, G. Hales¹, J. Amin¹, E. van Schiack², L. Bacheler³, B. Winters², D. Cooper¹, S. Emery¹
1NCHECR, Sydney, Australia; ²Virco BVBA, Mechelen, Belgium; ³VircoLab, Durham, USA

HIV drug resistance testing (RT) provides information of susceptibility to antiretrovirals. However it does not incorporate a measure of drug exposure. We assessed associations between 48 week clinical outcome and a range of covariates including normalised inhibitory quotient (NIQ).

87 HIV infected individuals were assigned a new boosted PI regimen by physician choice depending on RT result. PI therapy consisted of lopinavir, indinavir, saquinavir and amprenavir in 50%, 32%, 11% and 6% respectively. Fold Change (FC) in chosen PI was determined from RT at baseline with trough drug concentration (C_min) determined at week 4. NIQ was derived individually by the logarithm ratio of C_min/FC divided by the fixed ratio of population mean C_min/Virco clinical cut off. Viral load (VL) response over 48 weeks was correlated with baseline VL, FC, C_min, NIQ and selected PI.

Median baseline VL was 4.3 log. Median change in VL was 0.83 log at week 48. In multivariate analysis, baseline VL and NIQ were associated with change in VL from baseline at week 48 (p=0.012 and 0.003 respectively). FC, C_min, and selected PI were not significantly associated with VL changes. When dividing NIQ into inter-quartile groups, percentage with undetectable VL (<400 copies/ml) at week 48 were 18%, 58%, 56% and 76% respectively (p=0.002).

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. These prospective results support the use of a NIQ at week four, as a tool in predicting response to therapy in this setting.

SESSION 6: RESISTANCE AND PHARMACOKINETICS

2004-11-14
PL6.6

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