A randomized clinical trial evaluating therapeutic drug monitoring (TDM) for protease inhibitor-based regimens in antiretroviral-experienced HIV-infected individuals: week 48 results of the A5146 study.

TitleA randomized clinical trial evaluating therapeutic drug monitoring (TDM) for protease inhibitor-based regimens in antiretroviral-experienced HIV-infected individuals: week 48 results of the A5146 study.
Publication TypeJournal Article
Year of Publication2011
AuthorsAlbrecht M, A Mukherjee L, Tierney C, Morse GD, Dykes C, Klingman KL, Demeter LM
JournalHIV Clin Trials
Volume12
Issue4
Pagination201-14
Date Published2011 Jul-Aug
ISSN1528-4336
KeywordsAdult, CD4 Lymphocyte Count, Drug Monitoring, Female, Follow-Up Studies, HIV Infections, HIV Protease Inhibitors, HIV-1, Humans, Male, Middle Aged, Viral Load
Abstract

BACKGROUND: We devised an open-label, randomized trial to evaluate whether therapeutic drug monitoring (TDM) of protease inhibitors (PIs) and dose escalation based upon a normalized inhibitory quotient (NIQ), which integrates PI trough concentration and drug resistance, could improve virologic outcome in PI-experienced patients with treatment failure. Secondary analyses through 48 weeks are presented.

METHODS: Eligible HIV-infected subjects with a screening viral load of ≥ 1000 copies/mL initiated a new PI-based regimen at entry and had NIQ performed at week 2. Subjects with an NIQ ≤1 were randomized at week 4 to a standard-of-care (SOC) arm or TDM arm featuring PI dose escalation.

RESULTS: One hundred and eighty-three subjects were randomized. There was no significant treatment difference in change from randomization to week 48 in HIV-1 RNA [ P = .13, median (25th, 75th percentile log10 copies/mL change): -0.03 (-0.74, 0.62) with TDM and 0.11 (-2.3, 0.82) with SOC]. In subgroup analysis, patients with ≥ 0.69 active PIs benefited from TDM compared to those with <0.69 active PIs ( P = .05).

CONCLUSIONS: While the TDM strategy of PI dose escalation did not improve virologic response at week 48 overall, in subgroup analysis, TDM favorably impacted virologic outcome in subjects taking PI-based regimens with moderate antiviral activity.

DOI10.1310/HCT1204-201
Alternate JournalHIV Clin Trials
PubMed ID22044856
PubMed Central IDPMC3328407
Grant ListAI-04637 / AI / NIAID NIH HHS / United States
AI-25859 / AI / NIAID NIH HHS / United States
AI-25915 / AI / NIAID NIH HHS / United States
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