The human immunodeficiency virus-1 (HIV-1) enters target cells by binding its envelope glycoprotein gp120 to the CD4 receptor and/or coreceptors such as C-C chemokine receptor type 5 (CCR5; R5) and C-X-C chemokine receptor type 4 (CXCR4; X4), and R5-tropic viruses predominate during the early stages of infection. CCR5 antagonists bind to CCR5 to prevent viral entry. Maraviroc (MVC) is the only CCR5 antagonist currently approved by the United States Food and Drug Administration, the European Commission, Health Canada, and several other countries for the treatment of patients infected with R5-tropic HIV-1. MVC has been shown to be effective at inhibiting HIV-1 entry into cells and is well tolerated. With expanding MVC use by HIV-1-infected humans, different clinical outcomes post-approval have been observed with MVC monotherapy or combination therapy with other antiretroviral drugs, with MVC use in humans infected with dual-R5- and X4-tropic HIV-1, infected with different HIV-1 genotype or infected with HIV-2. This review discuss the role of CCR5 in HIV-1 infection, the development of the CCR5 antagonist MVC, its pharmacokinetics, pharmacodynamics, drug-drug interactions, and the implications of these interactions on treatment outcomes, including viral mutations and drug resistance, and the mechanisms associated with the development of resistance to MVC. This review also discusses available studies investigating the use of MVC in the treatment of other diseases such as cancer, graft-versus-host disease, and inflammatory diseases.

Table 2

Interaction of MVC with other drugs

Drugs	Net effect on CYP3A4	Effect on MVC concentrations	Recommended MVC dosage
Protease inhibitors
Saquinavir92	Inhibits	Increase by 332%	150 mg/kg twice daily
Lopinavir/ritonavir92	Inhibits	Increase by 128%	150 mg/kg twice daily
Atazanavir92	Inhibits	Increase by 267%	150 mg/kg twice daily
Ritonavir92	Inhibits	Increase by 209%	150 mg/kg twice daily
Darunavir/ritonavir93	Inhibits	Increase by 229%	150 mg/kg twice daily
Tipranavir/ritonavir92	Inhibits	No effect	300 mg/kg twice daily
Fosamprenavir/ritonavir94	Inhibits	Increased by 152%	150 mg/kg twice daily
Nucleoside/nucleotide analog reverse-transcriptase inhibitors
Lamivudine/zidovudine96	N/A	No effect	300 mg/kg twice daily
Tenofovir95	N/A	No effect	300 mg/kg twice daily
Non-nucleoside reverse-transcriptase inhibitors
Efavirenz98,99	Induces	Decrease by 25%–40%	600 mg/kg twice daily
Etravirine93	Induces	Decrease by 60%	600 mg/kg twice daily
Lersivirine102	Induces	Increase by 3.4%	300 mg/kg twice daily
Nevirapine99	Induces	Increase by 101%	150 mg/kg twice daily
Integrase inhibitors
Raltegravir103	Induces	Decrease by 20%	300 mg/kg twice daily
Elvitegravir/ritonavir105	Inhibits	Increase by 215%	150 mg/kg twice daily
Other (non-HIV) drugs
Ethinyloestradiol/leveonorgestrel96	N/A	No effect	300 mg/kg twice daily
Ethanol107	N/A	No effect	300 mg/kg twice daily
Ketaconazole92	Inhibits	Increase by 338%	150 mg/kg twice daily
Cotrimoxazole95	Inhibits	No effect	300 mg/kg twice daily
Boceprevir108	Induces	Increase by 300%	150 mg/kg twice daily
Telaprevir108	Inhibits	Increase by 9%	300 mg/kg twice daily

Abbreviations: MVC, maraviroc; CYP3A4, cytochrome P450-3A4; N/A, not available.

Table 3

Mutations associated with resistance to MVC

Mutations	HIV region	Specimens
Mutations found in clinical specimens
G11R110	V3 of gp120	Plasma
P13R110	V3 of gp120	Plasma
A25K110	V3 of gp120	Plasma
A316T112,118	V3 of gp120	Primary clinical isolates and plasma
P/T308H116	V3 of gp120	Plasma
T320H116	V3 of gp120	Plasma
I322aV116	V3 of gp120	Plasma
D407G116	V4 of gp120	Plasma
V489I116	C5 of gp120	Plasma
I20F + Y21I110	V3 of gp120	Plasma
Mutations found in vitro
A319S112	V3 of gp120	Primary clinical isolates
V169M113	V2 of gp120	HIV strain CC1/85
N192K113	V2 of gp120	HIV strain CC1/85
L317W113	V3 of gp120	HIV strain CC1/85
I408A113	V4 of gp120	HIV strain CC1/85
D462N113	V5 of gp120	HIV strain CC1/85
N463T113	V5 of gp120	HIV strain CC1/85
S464T113	V5 of gp120	HIV strain CC1/85
N465aD113	V5 of gp120	HIV strain CC1/85
L820I113	gp41	HIV strain CC1/85
I829V113	gp41	HIV strain CC1/85
Y837C113	gp41	HIV strain CC1/85
T199K/T275M114	C2 of gp120	HIV-1JR-FL-P17 and/or HIV-1V3Lib-P17
T275M114	C2 of gp120	HIV-1JR-FL-P17 and/or HIV-1V3Lib-P17
I304V114	V3 of gp120	HIV-1JR-FL-P17 and/or HIV-1V3Lib-P17
F312W114	V3 of gp120	HIV-1JR-FL-P17 and/or HIV-1V3Lib-P17
T314A114	V3 of gp120	HIV-1JR-FL-P17 and/or HIV-1V3Lib-P17
E317D114	V3 of gp120	HIV-1JR-FL-P17 and/or HIV-1V3Lib-P17