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

Babafemi Taiwo*, Edward P. Acosta, Patrick Ryscavage, Baiba Berzins, Darlene Lu, Jay Lalezari, Jose Castro, Oluwatoyin Adeyemi, Daniel R. Kuritzkes, Joseph J. Eron, Athe Tsibris, Susan Swindells

*Corresponding author for this work

Research output: Contribution to journalArticle

17 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)167-173
Number of pages7
JournalJournal of Acquired Immune Deficiency Syndromes
Volume64
Issue number2
DOIs
StatePublished - Oct 1 2013

Keywords

  • Darunavir
  • Maraviroc
  • Nucleos(t)ide sparing
  • Pharmacokinetics
  • Viral dynamics

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

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    Taiwo, B., Acosta, E. P., Ryscavage, P., Berzins, B., Lu, D., Lalezari, J., Castro, J., Adeyemi, O., Kuritzkes, D. R., Eron, J. J., Tsibris, A., & Swindells, S. (2013). 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. Journal of Acquired Immune Deficiency Syndromes, 64(2), 167-173. https://doi.org/10.1097/QAI.0b013e3182a03d95