Treatment of HIV Infection
Maraviroc is used in conjunction with other antiretroviral agents for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in antiretroviral-naive (have not previously received antiretroviral therapy) or antiretroviral-experienced (previously treated) adults infected with CCR5-tropic HIV-1.
Coreceptor tropism testing (assay detects CCR5- and CXCR4-using virus; results reported as CCR5-tropic, CXCR4-tropic, or dual/mixed-tropic HIV-1) is required for appropriate use of maraviroc.
The manufacturer advises that the following factors be considered when initiating therapy with maraviroc. Only adults infected with CCR5-tropic HIV-1 should receive maraviroc. Tropism testing must be conducted on a current sample using a highly sensitive assay that can identify patients who are appropriate candidates for maraviroc; low levels of CXCR4-tropic or dual/mixed-tropic HIV-1 not detected at screening are associated with virologic failure. Maraviroc is not recommended for use in patients with CXCR4-tropic or dual/mixed HIV-1 infection; data from a phase 2 study indicate the virologic response to the drug was minimal in those who had dual/mixed HIV-1 infection at the time of study enrollment.
Safety and efficacy of maraviroc have not been established in pediatric patients.
The most appropriate antiretroviral regimen cannot be defined for each clinical scenario, and selection of specific antiretroviral agents for use in multiple-drug regimens should be individualized based on information regarding antiretroviral potency, potential rate of development of resistance, known toxicities, and potential for pharmacokinetic interactions as well as virologic, immunologic, and clinical characteristics of the patient. For information on the general principles and guidelines for use of antiretroviral therapy, including specific recommendations for initial therapy in antiretroviral-naive patients and recommendations for changing antiretroviral regimens,
Antiretroviral-naive Adults and Adolescents
The US Department of Health and Human Services (HHS) Panel on Antiretroviral Guidelines for Adults and Adolescents states that maraviroc is not recommended for initial treatment regimens in antiretroviral-naive adults or adolescents because a coreceptor tropism assay should be performed before the drug is initiated, there is no virologic benefit compared with recommended regimens, and a twice-daily dosing regimen is required.
Safety and efficacy of maraviroc in antiretroviral-naive adults with CCR5-tropic HIV-1 infection is being evaluated in an ongoing randomized, double-blind, multicenter study (study A4001026; NCT00098293; MERIT study). Adults enrolled in this study had baseline HIV-1 RNA levels of 2000 copies/mL or greater, had received no antiretroviral therapy for at least 14 days, did not have a recent or active opportunistic infection, did not have primary HIV-1 infection, and did not have phenotypic or genotypic resistance to zidovudine, lamivudine, or efavirenz. Over 600 patients (mean age 36-37 years [range 18-77 years], 71-72% male, 55-57% white, 34-37% black, median baseline plasma HIV-1 RNA level 4.9 log10 copies/mL, median baseline CD4 T-cell count 241-254 cells/mm) were randomized to received maraviroc 300 mg once daily, maraviroc 300 mg twice daily, or efavirenz 600 mg once daily in conjunction with lamivudine and zidovudine. At 16 weeks, the maraviroc 300 mg once daily regimen did not meet the criteria to demonstrate non-inferiority and the regimen was discontinued.
At 96 weeks, 59% of those receiving maraviroc 300 mg twice daily in conjunction with lamivudine and zidovudine and 63% of those receiving efavirenz in conjunction with lamivudine and zidovudine had plasma HIV-1 RNA levels less than 50 copies/mL; 64% of those receiving either regimen had plasma HIV-1 RNA levels less than 400 copies/mL. The median increase from baseline CD4 T-cell count was 184 cells/mm in those receiving maraviroc compared with 155 cells/mm in those receiving efavirenz. Virologic failure (plasma HIV-1 RNA did not remain suppressed) was reported in 13-14 or 7-8% of those receiving maraviroc in conjunction with lamivudine and zidovudine or efavirenz in conjunction with lamivudine and zidovudine, respectively.
Antiretroviral-experienced Adults and Adolescents
Maraviroc is being evaluated in 2 randomized, double-blind, multicenter phase 3 studies (studies A4001027, A4001028; NCT0098306, NCT00098722; MOTIVATE 1 and 2) in antiretroviral-experienced adults infected with CCR5-tropic HIV-1. Adults enrolled in these studies had baseline HIV-1 RNA levels greater than 5000 copies/mL despite at least 6 months prior treatment with antiretroviral regimens that included at least one agent from 3 classes of antiretroviral agents (at least 1 NRTI, 1 NNRTI, 2 PIs, and/or enfuvirtide) or had documented resistance to at least one drug in each class of antiretroviral agents. Over 600 patients (mean age 46 years [range 21-73 years]; 89-90% male; 85% white; 12% black; mean baseline plasma HIV-1 RNA level 4.85-4.86 log10 copies/mL; median baseline CD4 T-cell count 167-171 cells/mm) received an optimized background antiretroviral regimen (OBR; consists of 3-6 antiretroviral agents selected on the basis of the individual's prior antiretroviral treatment and results of baseline genotypic and phenotypic viral resistance testing) and were randomized to receive maraviroc twice daily in conjunction with the OBR or the OBR alone. Analysis at 48 weeks indicated that maraviroc (300 mg twice daily) added to an OBR resulted in greater decreases in plasma HIV-1 RNA levels (-1.84 log10 copies/mL) than the OBR alone (-0.78 log10 copies/mL). At 48 weeks, 56 or 46% of those receiving maraviroc twice daily in conjunction with the OBR and 22 or 17% of those receiving the OBR alone had plasma HIV-1 RNA levels less than 400 or 50 copies/mL, respectively. In addition, the mean increase from baseline CD4 T-cell count at 48 weeks was greater in patients receiving maraviroc twice daily in conjunction with an OBR (increase of 124 cells/mm) than in those receiving the OBR alone (increase of 60 cells/mm).
Maraviroc also was evaluated in a randomized, double-blind, phase 2 study (A4001029; NCT00098748) in antiretroviral-experienced adults infected with dual/mixed tropic HIV-1. All patients received an OBR (3-6 antiretrovirals with or without low-dose ritonavir) and were randomized to receive maraviroc in conjunction with the OBR or the OBR alone. At week 24, the mean increase in CD4 T-cell counts was greater in those receiving maraviroc and the OBR compared with those receiving the OBR alone; however, the mean decrease in plasma HIV-1 RNA levels was similar in both groups.
Postexposure Prophylaxis following Occupational Exposure to HIV
Maraviroc is used in conjunction with other antiretrovirals for postexposure prophylaxis of HIV infection following occupational exposure (PEP) in health-care personnel and other individuals exposed via percutaneous injury (e.g., needlestick, cut with sharp object) or mucous membrane or nonintact skin (e.g., chapped, abraded, dermatitis) contact with blood, tissue, or other body fluids that might contain HIV.
The US Public Health Service (USPHS) states that the preferred regimen for PEP following an occupational exposure to HIV is a 3-drug regimen of raltegravir used in conjunction with emtricitabine and tenofovir disoproxil fumarate (tenofovir DF) (may be administered as the fixed combination emtricitabine/tenofovir DF; Truvada). These experts state that maraviroc is one of several alternative agents that may be used in conjunction with other antiretrovirals in PEP regimens, but should be used only with expert consultation.
Because management of occupational exposures to HIV is complex and evolving, consultation with an infectious disease specialist, clinician with expertise in administration of antiretroviral agents, and/or the National Clinicians' Postexposure Prophylaxis Hotline (PEPline at 888-448-4911) is recommended whenever possible. However, initiation of PEP should not be delayed while waiting for expert consultation.
For information on types of occupational exposure to HIV and associated risk of infection, management of occupational exposure to HIV, efficacy and safety of postexposure prophylaxis, and recommendations regarding PEP,