Gill Hales | PubMed Health

PubMed2006

Nonnucleoside reverse transcriptase inhibitor fold change or plasma concentration as a predictor of virological response over 48 weeks in highly treatment experienced HIV-positive individuals.

The nonnucleoside reverse transcriptase inhibitors (NNRTI) have low genetic barriers to resistance. Resistance can sometimes be overcome by increasing drug exposure. We assessed factors associated with 48-week virological response in treatment-experienced individuals receiving NNRTI therapy including resistance testing results and plasma drug exposure. Of 62 individuals assigned a new NNRTI-based regimen following resistance testing therapy consisted of efavirenz in 35 (56%) and nevirapine in 27 (44%) individuals. NNRTI fold change (FC) was determined from resistance test at baseline and plasma drug concentration at week 4. Mean time weighted change from baseline VL was -0.68 log over 48 weeks. Significant associations with change from baseline VL included baseline VL and FC whereas plasma drug concentration was not associated. In this cohort of highly treatment-experienced individuals treated with NNRTI regimens, we did not observe a significant association between NNRTI plasma concentration and virological response.

Alkynes↗

PubMed2005

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. DESIGN: 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. CONCLUSION: 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.

Antiretroviral Therapy, Highly Active↗