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

Research output: Contribution to journalArticle

17 Citations (Scopus)

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

Fingerprint

Ritonavir
HIV-1
efavirenz
Pharmacokinetics
Lopinavir
Viral Load
Confidence Intervals
Reverse Transcriptase Inhibitors
Darunavir
maraviroc
CD4 Lymphocyte Count

Keywords

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

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

Cite this

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

In: Journal of Acquired Immune Deficiency Syndromes, Vol. 64, No. 2, 01.10.2013, p. 167-173.

Research output: Contribution to journalArticle

Taiwo, Babafemi ; Acosta, Edward P. ; Ryscavage, Patrick ; Berzins, Baiba ; Lu, Darlene ; Lalezari, Jay ; Castro, Jose ; Adeyemi, Oluwatoyin ; Kuritzkes, Daniel R. ; Eron, Joseph J. ; Tsibris, Athe ; Swindells, Susan. / 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. In: Journal of Acquired Immune Deficiency Syndromes. 2013 ; Vol. 64, No. 2. pp. 167-173.
@article{82b581c8af9043c6b15225311add2903,
title = "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",
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.",
keywords = "Darunavir, Maraviroc, Nucleos(t)ide sparing, Pharmacokinetics, Viral dynamics",
author = "Babafemi Taiwo and Acosta, {Edward P.} and Patrick Ryscavage and Baiba Berzins and Darlene Lu and Jay Lalezari and Jose Castro and Oluwatoyin Adeyemi and Kuritzkes, {Daniel R.} and Eron, {Joseph J.} and Athe Tsibris and Susan Swindells",
year = "2013",
month = "10",
day = "1",
doi = "10.1097/QAI.0b013e3182a03d95",
language = "English (US)",
volume = "64",
pages = "167--173",
journal = "Journal of Acquired Immune Deficiency Syndromes",
issn = "1525-4135",
publisher = "Lippincott Williams and Wilkins",
number = "2",

}

TY - JOUR

T1 - 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

AU - Taiwo, Babafemi

AU - Acosta, Edward P.

AU - Ryscavage, Patrick

AU - Berzins, Baiba

AU - Lu, Darlene

AU - Lalezari, Jay

AU - Castro, Jose

AU - Adeyemi, Oluwatoyin

AU - Kuritzkes, Daniel R.

AU - Eron, Joseph J.

AU - Tsibris, Athe

AU - Swindells, Susan

PY - 2013/10/1

Y1 - 2013/10/1

N2 - 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.

AB - 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.

KW - Darunavir

KW - Maraviroc

KW - Nucleos(t)ide sparing

KW - Pharmacokinetics

KW - Viral dynamics

UR - http://www.scopus.com/inward/record.url?scp=84885207300&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84885207300&partnerID=8YFLogxK

U2 - 10.1097/QAI.0b013e3182a03d95

DO - 10.1097/QAI.0b013e3182a03d95

M3 - Article

C2 - 23797691

AN - SCOPUS:84885207300

VL - 64

SP - 167

EP - 173

JO - Journal of Acquired Immune Deficiency Syndromes

JF - Journal of Acquired Immune Deficiency Syndromes

SN - 1525-4135

IS - 2

ER -