A randomized trial of therapeutic drug monitoring of protease inhibitors in antiretroviral-experienced, HIV-1-infected patients.

TitleA randomized trial of therapeutic drug monitoring of protease inhibitors in antiretroviral-experienced, HIV-1-infected patients.
Publication TypeJournal Article
Year of Publication2009
AuthorsDemeter LM, Jiang H, A Mukherjee L, Morse GD, DiFrancesco R, DiCenzo R, Dykes C, Sista P, Bacheler L, Klingman K, Rinehart A, Albrecht M
JournalAIDS
Volume23
Issue3
Pagination357-68
Date Published2009 Jan 28
ISSN1473-5571
KeywordsAdult, Antiretroviral Therapy, Highly Active, Drug Administration Schedule, Drug Monitoring, Drug Resistance, Viral, Female, HIV Infections, HIV Protease Inhibitors, HIV-1, Humans, Male, Middle Aged, RNA, Viral, Treatment Outcome, Viral Load
Abstract

OBJECTIVE: Whether therapeutic drug monitoring of protease inhibitors improves outcomes in HIV-infected patients is controversial. We evaluated this strategy in a randomized, open-label clinical trial, using a normalized inhibitory quotient (NIQ), which incorporates drug exposure and viral drug resistance. NIQs < or = 1 may predict poor outcome and identify patients who could benefit from dose escalation.

DESIGN/METHODS: Eligible patients had a viral load > or =1000 copies/ml on a failing regimen, and began a new protease inhibitor containing regimen at entry. All FDA-approved protease inhibitors available during the study recruitment (June 2002-May 2006) were allowed. One hundred and eighty-three participants with NIQ < or = 1, on the basis of their week 2 protease inhibitor trough concentration and pre-entry drug resistance test, were randomized at week 4 to standard of care (SOC) or protease inhibitor dose escalation (TDM). The primary endpoint was change in log10 plasma HIV-1 RNA concentration from randomization to 20 weeks later.

RESULTS: Ninety-one patients were randomized to SOC and 92 to TDM. NIQs increased more in the TDM arm compared to SOC (+69 versus +25%, P = 0.01). Despite this, TDM and SOC arms showed no difference in outcome (+0.09 versus +0.02 log10, P = 0.17). In retrospective subgroup analyses, patients with less HIV resistance to their protease inhibitors benefited from TDM (P = 0.002), as did black and Hispanic patients (P = 0.035 and 0.05, respectively). Differences between black and white patients persisted when accounting for protease inhibitor susceptibility.

CONCLUSIONS: There was no overall benefit of TDM. In post hoc subgroup analyses, TDM appeared beneficial in black and Hispanic patients, and in patients whose virus retained some susceptibility to the protease inhibitors in their regimen.

DOI10.1097/QAD.0b013e32831f9148
Alternate JournalAIDS
PubMed ID19114860
PubMed Central IDPMC2798571
Grant ListAI-25859 / AI / NIAID NIH HHS / United States
AI-27665 / AI / NIAID NIH HHS / United States
AI-27761 / AI / NIAID NIH HHS / United States
AI-32782 / AI / NIAID NIH HHS / United States
AI-32783 / AI / NIAID NIH HHS / United States
AI-34853 / AI / NIAID NIH HHS / United States
AI-38855 / AI / NIAID NIH HHS / United States
AI-38858 / AI / NIAID NIH HHS / United States
AI-46370 / AI / NIAID NIH HHS / United States
AI-68634 / AI / NIAID NIH HHS / United States
AI-68636 / AI / NIAID NIH HHS / United States
AI-69411 / AI / NIAID NIH HHS / United States
AI-69415 / AI / NIAID NIH HHS / United States
AI-69419 / AI / NIAID NIH HHS / United States
AI-69423 / AI / NIAID NIH HHS / United States
AI-69424 / AI / NIAID NIH HHS / United States
AI-69428 / AI / NIAID NIH HHS / United States
AI-69432 / AI / NIAID NIH HHS / United States
AI-69434 / AI / NIAID NIH HHS / United States
AI-69439 / AI / NIAID NIH HHS / United States
AI-69450 / AI / NIAID NIH HHS / United States
AI-69452 / AI / NIAID NIH HHS / United States
AI-69471 / AI / NIAID NIH HHS / United States
AI-69472 / AI / NIAID NIH HHS / United States
AI-69474 / AI / NIAID NIH HHS / United States
AI-69477 / AI / NIAID NIH HHS / United States
AI-69484 / AI / NIAID NIH HHS / United States
AI-69494 / AI / NIAID NIH HHS / United States
AI-69495 / AI / NIAID NIH HHS / United States
AI-69501 / AI / NIAID NIH HHS / United States
AI-69511 / AI / NIAID NIH HHS / United States
AI-69513 / AI / NIAID NIH HHS / United States
AI-69532 / AI / NIAID NIH HHS / United States
AI-69556 / AI / NIAID NIH HHS / United States
M01 RR000044-440787 / RR / NCRR NIH HHS / United States
P30-AI-45008 / AI / NIAID NIH HHS / United States
RR-00032 / RR / NCRR NIH HHS / United States
RR-00044 / RR / NCRR NIH HHS / United States
RR-00047 / RR / NCRR NIH HHS / United States
RR-00051 / RR / NCRR NIH HHS / United States
RR-00075 / RR / NCRR NIH HHS / United States
RR-00096 / RR / NCRR NIH HHS / United States
U01 AI027659 / AI / NIAID NIH HHS / United States
U01 AI027659-18 / AI / NIAID NIH HHS / United States
U01 AI038858 / AI / NIAID NIH HHS / United States
U01 AI038858-09 / AI / NIAID NIH HHS / United States
U01 AI068636 / AI / NIAID NIH HHS / United States
U01 AI068636-04 / AI / NIAID NIH HHS / United States
U01 AI069511-03 / AI / NIAID NIH HHS / United States
UM1 AI069423 / AI / NIAID NIH HHS / United States