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Clin Infect Dis. 2016 Jul 1;63(1):122-32. doi: 10.1093/cid/ciw207. Epub 2016 Apr 5.

Maraviroc, as a Switch Option, in HIV-1-infected Individuals With Stable, Well-controlled HIV Replication and R5-tropic Virus on Their First Nucleoside/Nucleotide Reverse Transcriptase Inhibitor Plus Ritonavir-boosted Protease Inhibitor Regimen: Week 48 Results of the Randomized, Multicenter MARCH Study.

Collaborators (227)

Kelleher A, Merlin K, Yeung J, Fsadni B, Marks K, Suzuki K, Rismanto N, Salomon H, Rubio AE, Chibo D, Birch C, Harrigan R, Swenson L, Chan D, Berg T, Obermeier M, Kaiser R, Schuelter E, Sierra Aragon S, Luebke N, Coughlan S, Dean J, Sugiura W, Iwatani Y, Reyes Teran G, Avila S, Ruxrungtham K, Sirivichayakul S, Naphassanant M, Ubolyam S, Kaye S, Land S, Walker S, Haubrich R, DeJesus E, Emery S, Pett SL, Tu E, Silk D, Berthon-Jones N, Amin J, Espinosa N, Courtney-Vega K, Absar N, Haskelberg H, Robson R, Donaldson A, Losso M, Belloso W, Guelman D, Gambardella L, Valdovinos M, Gatell J, Arnaiz J, Beleta H, Ramos N, Targa M, Rockstroh J, Späth B, Boesecke C, Engelhardt A, Fisher M, Perry N, Clarke A, Gill J, Beckthold B, Clark A, Drummond F, Lefevre E, Corr S, Grant C, Lupo S, Peroni L, Italiano H, Sanchez M, De Paz Sierra M, Mejia R, Losso M, Viloria G, Parlante A, Bissio E, Luchetti P, Warley E, Vieni I, Porteiro N, Vilas C, Zarate A, Mayer G, Elliot J, Hagenauer M, Kelley M, Rowling D, Gibson A, Latch N, Tabrett C, Warzywoda E, Cooper D, Pett S, MacRae K, Sinclair B, Sinn K, Bloch M, Franic T, Vincent T, Stewart N, Jayewardene A, Dwyer D, Kok J, Assam D, Taylor J, King P, Orth D, Youds D, Sowden D, Johnston C, Murray S, Hehir J, Wadham S, Donohue W, Thompson J, Garsia R, Turnham G, Madden T, Woolley I, Gillies A, Bryant M, Gill J, Beckthold B, Walmsley S, Chan W, LeBlanc R, Lanteigne F, Mouawad R, Rahal I, Guber S, Ozturk S, Smith G, Halpenny R, Reko T, Robinette Hills J, Wolff M, Prazuck T, Laurent Hocqueloux F, Wolfgang J, Stephan C, Ebeling F, Rockstroh J, Boesecke C, Spath B, Engelhardt A, Ole Jensen BE, Feind C, Meyer-Olson D, Stoll M, Hoeper K, Beider R, Faetkenheur G, Thomas Baumgarten E, Baumgarten A, Ingiliz P, Wienbreyer A, Behrendt D, Nienkarken T, Stein J, Jessen H, Zedlack C, Mallon P, Simelane S, Assmann J, Ghavami-Kia B, Sugiura W, Imahashi M, Tanabe K, Yokomaku Y, Imamura J, Andrade-Villanueva J, Montes de Oca M, Gonzalez L, Ponce D, Mendoza A, Sierra-Madero J, Sanchez Hernandez JE, Jaime Ruiz Ballesteros E, Del Moral Ponce S, Mosqueda L, Lopez M, Horban A, Ignatowska A, Bakowska E, Pulik P, Sanz-Moreno J, Paredes R, Puig J, Domingo P, Gutierrez M, Gatell J, González-Cordón A, Callau P, Lopez Aldeguer J, Cuellar Tovar S, Leal Noval M, Rivas I, Delgado-Fernandez M, Ramon Arribas J, Miguel Castro J, Ruxrungtham K, Avihingsanon A, Maek-A-Nantawat W, Intasan J, Charoenporn W, Cuprasitrut T, Jaisomkom P, Pruksakaew K, Winston A, Mullaney S, Fisher M, Clarke A, Barbour L, Perry N, Richardson C, Fox J, Murray T, Leen C, Morris S, Satyajit D, Sandhu R, Tucker J.

Author information

1
The Kirby Institute, University of New South Wales, Sydney, Australia Medical Research Council Clinical Trials Unit, Institute of Clinical Trials and Methodology Clinical Research Group, Infection and Population Health, University College London, United Kingdom.
2
The Kirby Institute, University of New South Wales, Sydney, Australia.
3
Wojewodzki Szpital Zakazny Centrum Diagnostyki i Terapii AIDS, Warsaw, Poland.
4
Hospital Civil de Guadalajara "Fray Antonio Alcalde," Jalisco, Mexico.
5
Hospital General de Agudos J M Ramos Mejia Fundación IBIS Coordinacion de Investigacion Clinica Academica en Latinoamerica.
6
Fundación Infectologia de Atencion Ambulatoria, Buenos Aires, Argentina.
7
Instituto Nacional de Ciencias Medicas y Nutriciòn Salvador Zubiran, Tlalpan, Mexico.
8
Fundación IBIS Coordinacion de Investigacion Clinica Academica en Latinoamerica Hospital Italiano de Buenos Aires, Argentina.
9
The Kirby Institute, University of New South Wales, Sydney, Australia St Vincent's Hospital, Sydney, Australia.
10
British Columbia Centre for Excellence in HIV/AIDS, Vancouver, Canada.
11
ViiV Healthcare Ltd, London, United Kingdom.
12
Nagoya Medical Centre, Japan.
13
Fundacion Arriaran, Santiago, Chile.
14
Southern Alberta Clinic, Calgary, Canada.
15
Hospital Clinic de Barcelona, Spain.
16
Brighton and Sussex University Hospitals National Health Service Trust, Brighton, United Kingdom.
17
HIV Netherlands, Australia, Thailand Research Collaboration, Bangkok.
18
Orleans Hospital (Centre Hospitalier Regional D'Orleans Orleans La Source), France.
19
Institut für Virologie, Cologne, Germany.
20
Monash Medical Centre, Melbourne, Australia.
21
Fundacion Clinic Spain Clinical Trials Unit, Barcelona.
22
Department of Medicine I, University Hospital Bonn, Germany.
23
Mater Misericordiae University Hospital, Dublin, Ireland.

Abstract

BACKGROUND:

Alternative combination antiretroviral therapies in virologically suppressed human immunodeficiency virus (HIV)-infected patients experiencing side effects and/or at ongoing risk of important comorbidities from current therapy are needed. Maraviroc (MVC), a chemokine receptor 5 antagonist, is a potential alternative component of therapy in those with R5-tropic virus.

METHODS:

The Maraviroc Switch Study is a randomized, multicenter, 96-week, open-label switch study in HIV type 1-infected adults with R5-tropic virus, virologically suppressed on a ritonavir-boosted protease inhibitor (PI/r) plus double nucleoside/nucleotide reverse transcriptase inhibitor (2 N(t)RTI) backbone. Participants were randomized 1:2:2 to current combination antiretroviral therapy (control), or replacing the protease inhibitor (MVC + 2 N(t)RTI arm) or the nucleoside reverse transcriptase inhibitor backbone (MVC + PI/r arm) with twice-daily MVC. The primary endpoint was the difference (switch minus control) in proportion with plasma viral load (VL) <200 copies/mL at 48 weeks. The switch arms were judged noninferior if the lower limit of the 95% confidence interval (CI) for the difference in the primary endpoint was < -12% in the intention-to-treat (ITT) population.

RESULTS:

The ITT population comprised 395 participants (control, n = 82; MVC + 2 N(t)RTI, n = 156; MVC + PI/r, n = 157). Baseline characteristics were well matched. At week 48, noninferior rates of virological suppression were observed in those switching away from a PI/r (93.6% [95% CI, -9.0% to 2.2%] and 91.7% [95% CI, -9.6% to 3.8%] with VL <200 and <50 copies/mL, respectively) compared to the control arm (97.6% and 95.1% with VL <200 and <50 copies/mL, respectively). In contrast, MVC + PI/r did not meet noninferiority bounds and was significantly inferior (84.1% [95% CI, -19.8% to -5.8%] and 77.7% [95% CI, -24.9% to -8.4%] with VL <200 and <50 copies/mL, respectively) to the control arm in the ITT analysis.

CONCLUSIONS:

These data support MVC as a switch option for ritonavir-boosted PIs when partnered with a 2-N(t)RTI backbone, but not as part of N(t)RTI-sparing regimens comprising MVC with PI/r.

CLINICAL TRIALS REGISTRATION:

NCT01384682.

KEYWORDS:

HIV-1; antiretroviral; comorbidity; maraviroc; switch

PMID:
27048747
PMCID:
PMC5853584
DOI:
10.1093/cid/ciw207
[Indexed for MEDLINE]
Free PMC Article

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