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J Acquir Immune Defic Syndr. 2013 Oct 1;64(2):167-73. doi: 10.1097/QAI.0b013e3182a03d95.

Virologic response, early HIV-1 decay, and maraviroc pharmacokinetics with the nucleos(t)ide-free regimen of maraviroc plus darunavir/ritonavir in a pilot study.

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1
*Division of Infectious Diseases, Northwestern University, Chicago, IL; †Division of Clinical Pharmacology, University of Alabama, Birmingham, AL; ‡University of Maryland, Baltimore, MD; §Statistical and Data Analysis Section, Harvard School of Public Health, Boston, MA; ‖Quest Clinical Research, San Francisco, CA; ¶Division of Infectious Diseases, University of Miami, Miami, FL; #CORE Center, Chicago, IL; **Division of Infectious Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; ††Division of Infectious Diseases, University of North Carolina, Chapel Hill, NC; and ‡‡Division of Infectious Diseases, University of Nebraska, Omaha, NE.

Abstract

OBJECTIVE:

To address the need for nucleos(t)ide reverse transcriptase inhibitor (NRTI)-sparing regimens, we explored the virologic and pharmacokinetic characteristics of maraviroc plus ritonavir-boosted darunavir in a single-arm, open-label, 96-week study.

METHODS:

Twenty-four antiretroviral-naive R5 HIV-1-infected participants received maraviroc 150 mg and darunavir/ritonavir (DRV/r) 800/100 mg (MVC/DRV/r) once daily. The primary outcome was virologic failure (VF) = confirmed viral load (VL) >50 copies per milliliter at week 24 in the modified intent-to-treat population. To determine viral dynamics, participant-specific first- and second-phase empirical Bayes estimates were compared with decay rates from efavirenz (EFV) plus lopinavir/ritonavir, lopinavir/ritonavir plus 2NRTIs, and EFV plus 2NRTIs. Maraviroc plasma concentrations were determined at weeks 2, 4, 12, 24, and 48.

RESULTS:

Baseline median (Q1, Q3) CD4 count and VL were 455 (299, 607) cells per cubic millimeter and 4.62 (4.18, 4.80) log10 copies per milliliter, respectively. VF occurred in 3 of 24 participants {12.5% [95% confidence interval (CI): 2.7 to 32.4]} at week 24. One of these resuppressed, yielding a week 48 VF rate of 2/24 [8.3% (95% CI: 1.0 to 27.0)]. The week 48 failures were 2 of the 4 participants (50%) with baseline VL >100,000 copies per milliliter. Week 96 VF rate was 2/20 [10% (95% CI: 1.2 to 31.7)]. Phase 1 decay was faster with MVC/DRV/r than reported for ritonavir-boosted lopinavir plus 2NRTIs (P = 0.0063) and similar to EFV-based regimens. Individual maraviroc trough concentrations collected between 20 and 28 hours post dose (n = 59) was 13.7 to 130 ng/mL (Q1, 23.4 ng/mL; Q3, 46.5 ng/mL), and modeled steady-state concentration was 128 ng/mL.

CONCLUSIONS:

MVC/DRV/r 150/800/100 mg once daily has potential for treatment-naive patients with R5 HIV-1.

PMID:
23797691
PMCID:
PMC4208821
DOI:
10.1097/QAI.0b013e3182a03d95
[Indexed for MEDLINE]
Free PMC Article
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