AHFS Class:

• HIV Entry and Fusion Inhibitors 8:18.08.04

Generic Name(s):

• Maraviroc

Maraviroc, an antiretroviral agent, is a human immunodeficiency virus (HIV) entry inhibitor.1,6,8,200 The drug is a CC chemokine receptor type 5 (CCR5) antagonist.1,6,8,200

Treatment of HIV Infection

Maraviroc is used in combination with other antiretroviral agents in adults and pediatric patients weighing ≥2 kg who are infected with CC chemokine receptor 5 (CCR5)-tropic human immunodeficiency virus type 1 (HIV-1).1 Maraviroc is not recommended in patients with dual/mixed-tropic or C-X-C chemokine receptor 4 (CXCR4)-tropic HIV-1 infection.1

CCR5 tropism testing should be performed whenever use of maraviroc is being considered.1 Outgrowth of preexisting low levels of dual/mixed-tropic or CXCR4-tropic HIV-1 not detected during initial screening has been associated with virologic failure in patients receiving maraviroc.1

Maraviroc is not recommended as initial therapy in an antiretroviral regimen because of the need for CCR5 tropism testing before beginning therapy.200 Maraviroc can be used as part of an optimized regimen in the management of patients with virologic failure with a second regimen and beyond with no detectable CXCR4-using virus.200,201 Selection of an optimized antiretroviral regimen should be individualized based on factors such as virologic efficacy, toxicity, current and previous drug-resistance test results, and availability of antiretrovirals with a high barrier to resistance.200

Clinical Experience

Antiretroviral-naïve Adults

The MERIT (Maraviroc versus Efavirenz in Treatment-Naïve Patients) study was a randomized, double-blind, multicenter trial of maraviroc in antiretroviral-naive adults with CCR5-tropic HIV-1 infection.1,15,18 Adults enrolled in this study had baseline HIV-1 RNA levels ≥2000 copies/mL and did not previously receive any antiretroviral therapy for more than 14 days; the study participants also did have a recent or active opportunistic infection, primary HIV-1 infection, and phenotypic or genotypic resistance to zidovudine, lamivudine, or efavirenz.1,15 Patients were randomized to receive maraviroc 300 mg once daily, maraviroc 300 mg twice daily, or efavirenz 600 mg once daily, all in conjunction with lamivudine and zidovudine.1,15 Median baseline HIV-1 RNA levels were 4.9 log₁₀ copies/mL with median CD4+ T-cell counts of 241-254 cells/mm³.1 Co- primary end points were the proportion of patients with HIV-1 RNA <400 copies/mL and <50 copies/mL at 48 weeks.15

At 16 weeks, the maraviroc 300 mg once daily regimen did not meet the prespecified criteria to demonstrate non-inferiority and was therefore discontinued.1,15

At 48 weeks, 70.6 and 73.1% of patients treated with maraviroc and efavirenz, respectively, achieved HIV-1 RNA levels <400 copies/mL, demonstrating noninferiority of maraviroc for this end point.15 At 48 weeks, 65.3 and 69.3% of patients treated with maraviroc and efavirenz, respectively, had plasma HIV-1 RNA levels <50 copies/mL; however, maraviroc did not meet the noninferiority criteria for HIV-1 RNA levels <50 copies/mL.15

At 96 weeks, 59% of those receiving maraviroc 300 mg twice daily and 63% of those receiving efavirenz had plasma HIV-1 RNA levels <50 copies/mL;1,18 64% of those receiving either regimen had plasma HIV-1 RNA levels <400 copies/mL.1 The median increase from baseline CD4+ T-cell count at 96 weeks was 184 cells/mm³ in those receiving maraviroc compared with 155 cells/mm³ in those receiving efavirenz.1 Virologic failure (plasma HIV-1 RNA did not remain suppressed at <400 or <50 copies/mL) was reported in 13-14% or 7-8% of those receiving maraviroc or efavirenz, respectively.1

Antiretroviral-experienced Adults

MOTIVATE-1 and MOTIVATE-2 (Maraviroc versus Optimized Therapy in Viremic Antiretroviral Treatment-Experienced Patients) were 2 randomized, double-blind, multicenter, phase 3 studies in antiretroviral-experienced adults infected with CCR5-tropic HIV-1.1,17 Adults enrolled in these studies had baseline HIV-1 RNA levels >5000 copies/mL despite at least 6 months of prior treatment with antiretroviral regimens that included at least 1 agent from 3 classes of antiretroviral agents (at least 1 nucleoside reverse transcriptase inhibitor [NRTI], 1 nonnucleoside reverse transcriptase inhibitor [NNRTI], 2 protease inhibitors [PIs], and/or enfuvirtide) or had documented resistance to at least a single drug in each class of antiretroviral agents.1,17 A total of 1049 patients were randomized to treatment with either maraviroc 300 mg once daily, maraviroc 300 mg twice daily, or placebo, all with an optimized background regimen (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).17 In MOTIVATE-1 and MOTIVATE-2, mean baseline HIV-1 RNA levels were 4.85 and 4.86 log₁₀ copies/mL, respectively, and median baseline CD4+ T-cell counts were 159 and 176 cells/mm³, respectively.17 The primary end point was mean change from baseline in HIV-1 RNA levels (log₁₀ copies/mL) at 48 weeks.17

Pooled analysis at 48 weeks indicated that treatment with maraviroc 300 mg twice daily resulted in a greater decrease in plasma HIV-1 RNA levels (<1.84 log₁₀ copies/mL) compared with placebo (<0.78 log₁₀ copies/mL).1 At 48 weeks, achievement of plasma HIV-1 RNA levels <400 or <50 copies/mL occurred in 56 or 46%, respectively, of those receiving maraviroc twice daily, 52 or 43%, respectively, of those receiving maraviroc once daily, and 22 or 17%, respectively, of those receiving placebo.1,17 In addition, the mean increase from baseline CD4+ T-cell count at 48 weeks was greater in patients receiving maraviroc twice daily (124 cells/mm³) than in those receiving placebo plus an optimized background regimen (60 cells/mm³).1,17

Results at 96 weeks for MOTIVATE-1 and MOTIVATE-2 were also reported.300 Among patients responding at 48 weeks with HIV-1 RNA levels <50 copies/mL, 81 and 87% of patients in the maraviroc once daily and maraviroc twice daily groups, respectively, maintained this response.300 Median changes in CD4+ T-cell count from baseline for the maraviroc once- and twice- daily groups were 89 and 113 cells/mm³, respectively, at 96 weeks.300

Antiretroviral-experienced Pediatric Patients

Efficacy and safety of maraviroc for the treatment of HIV infection in pediatric patients were evaluated in an open-label, multicenter study that included 103 antiretroviral-experienced children ≥2 to <18 years of age (mean age 10 years) with CCR5-tropic HIV infection who had baseline plasma HIV-1 RNA levels >1000 copies/mL.1,24 Mean baseline plasma HIV-1 RNA level was 4.4 log₁₀copies/mL with a mean CD4+ T-cell count of 551 cells/mm³.1,24 All patients received maraviroc twice daily in conjunction with an optimized background regimen (3-5 antiretrovirals selected based on the patient's prior antiretroviral treatment and results of resistance testing).1,24 Initial maraviroc dosage was selected based on body surface area and whether the patient was receiving potent cytochrome P-450 (CYP) 3A inhibitors and/or inducers concomitantly.1,24 Dosage was then adjusted to achieve a target average maraviroc plasma concentration of 100 ng/mL.24 At 48 weeks, 48% of patients achieved plasma HIV-1 RNA levels <48 copies/mL and 65% achieved plasma HIV-1 RNA levels <400 copies/mL.1,24 The mean CD4+ T-cell count (percentage) increase from baseline to week 48 was 247 cells/mm³ (5%).1

Clinical Perspective

Therapeutic options for the treatment and prevention of HIV infection and recommendations for use of antiretrovirals are continuously evolving.200 Antiretroviral therapy (ART) is recommended for all individuals with HIV regardless of CD4 counts, and should be initiated as soon as possible after diagnosis of HIV and continued indefinitely.200 The primary goals of ART are to achieve and maintain durable suppression of HIV viral load (as measured by plasma HIV-1 RNA levels) to a level below which drug-resistance mutations cannot emerge (i.e., below detectable limits), restore and preserve immunologic function, reduce HIV-related morbidity and mortality, improve quality of life, and prevent transmission of HIV.200 While the most appropriate antiretroviral regimen cannot be defined for each clinical scenario, the US Department of Health and Human Services (HHS) Panel on Antiretroviral Guidelines for Adults and Adolescents, HHS Panel on Antiretroviral Therapy and Medical Management of Children Living with HIV, and HHS Panel on Treatment of Pregnant Women with HIV Infection and Prevention of Perinatal Transmission, have developed comprehensive guidelines that provide information on selection and use of antiretrovirals for the treatment or prevention of HIV infection.200,201,202 Because of the complexity of managing patients with HIV, it is recommended that clinicians with HIV expertise be consulted when needed.200,201,202

The use of combination antiretroviral (ARV) regimens, generally including 3 drugs from 2 or more drug classes, is currently recommended to achieve viral suppression.200,201 In both treatment-naïve adults and children, an initial ARV regimen generally consists of 2 nucleoside reverse transcriptase inhibitors (NRTIs) administered in combination with a third active ARV drug from one of 3 drug classes: an integrase strand transfer inhibitor (INSTI), a non-nucleoside reverse transcriptase inhibitor (NNRTI), or a protease inhibitor (PI) with a pharmacokinetic enhancer (also known as a booster; the 2 drugs used as boosters are cobicistat and ritonavir).200,201 Selection of an initial ARV regimen should be individualized based on factors such as virologic efficacy, toxicity, pill burden, dosing frequency, drug-drug interaction potential, resistance-test results, comorbid conditions, access, and cost.200 In patients with comorbid infections (e.g., hepatitis B, tuberculosis), ARV regimen selection should also consider the potential for activity against other present infections and timing of initiation relative to other anti-infective regimens.200

In the 2023 HHS adult and adolescent HIV treatment guideline, maraviroc is listed among other drugs with novel mechanisms of action that can be considered in patients who have not previously received these drugs; these drugs can be included as part of a fully active ARV regimen for treatment of HIV infection with virologic failure, including following failure of a second-line ARV regimen and beyond.200 Patients treated with maraviroc should have no detectable CXCR4-using virus, confirmed using a viral tropism assay.200 Based on results of clinical trials and rates of virologic failure, optimization strategies with maraviroc plus a boosted PI or maraviroc plus raltegravir are not recommended.200

In the 2023 HHS pediatric HIV treatment guideline, maraviroc is listed as an option to constitute part of a fully active ARV regimen for treatment of HIV infection with virologic failure.201 Maraviroc is recommended as an addition to a regimen after failure of ARV regimens that included NRTI(s), NNRTI(s), and PI(s) and if there is minimal NRTI antiviral activity.201 Although maraviroc is indicated for patients >2 kg, lack of data on its use in neonates and risk of drug interactions may limit its use in infants born to mothers with multidrug-resistant HIV-1 that is CCR5-tropic.201

In the 2023 HHS perinatal HIV treatment guideline, maraviroc is not recommended as initial therapy before or during pregnancy for antiretroviral-naïve patients.202 Maraviroc is not recommended in other settings of pregnancy or in nonpregnant people who are trying to conceive, except under special circumstances.202 Maraviroc can be continued with no dosage adjustments as part of a fully suppressive, well-tolerated existing ARV regimen if pregnancy occurs during treatment.202

Postexposure Prophylaxis following Occupational Exposure to HIV

Maraviroc is only recommended for use in postexposure prophylaxis of HIV infection following occupational exposure† (PEP) in health-care personnel and other individuals after expert consultation.199

Clinical Perspective

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^®).199 Several alternative regimens include an INSTI, NNRTI, or PI and 2 NRTIs (dual NRTIs).199 The preferred dual NRTI option for use in PEP regimens is emtricitabine and tenofovir DF (may be administered as the fixed combination emtricitabine/tenofovir DF; Truvada^®); alternative dual NRTIs are tenofovir DF and lamivudine, lamivudine and zidovudine (may be administered as the fixed combination lamivudine/zidovudine; Combivir^®), or zidovudine and emtricitabine.199 These experts also 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.199

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.199 However, initiation of PEP should not be delayed while waiting for expert consultation.199

Postexposure Prophylaxis following Nonoccupational Exposure to HIV

Maraviroc is only recommended for use in postexposure prophylaxis of HIV infection following nonoccupational exposure† (nPEP; e.g., after sexual, injection drug use, or other nonoccupational exposures) after expert consultation.198

Clinical Perspective

When nPEP is indicated following a nonoccupational exposure to HIV, the US Centers for Disease Control and Prevention (CDC) states that the preferred regimen in adults and adolescents >13 years of age with normal renal function is either raltegravir or dolutegravir used in conjunction with emtricitabine and tenofovir DF (administered as the fixed combination emtricitabine/tenofovir DF; Truvada^®).198 The alternative nPEP regimen recommended in these patients is ritonavir-boosted darunavir used in conjunction with emtricitabine/tenofovir DF (Truvada^®).198 The CDC guidelines state that maraviroc is an alternative antiretroviral that can be used in nPEP regimens, but should be used in such regimens only with expert consultation.198

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 if nPEP is indicated in certain exposed individuals (e.g., pregnant women, children, those with medical conditions such as renal impairment) or if an antiretroviral regimen not included in the CDC guidelines is being considered, the source virus is known or likely to be resistant to antiretrovirals, or the healthcare provider is inexperienced in prescribing antiretrovirals.198 However, initiation of nPEP should not be delayed while waiting for expert consultation.198

General

Pretreatment Screening

• Prior to initiation of maraviroc for treatment of human immunodeficiency virus type 1 (HIV-1), test all patients for CC chemokine receptor 5 (CCR5) tropism using a highly sensitive tropism assay.1
• Monitor serum concentrations of AST, ALT, and bilirubin prior to initiation of maraviroc.1

Patient Monitoring

• Monitor serum concentrations of AST, ALT, and bilirubin as clinically indicated during treatment with maraviroc.1
• Monitor for adverse cardiovascular events more closely in patients with cardiovascular comorbidities, risk factors for postural hypotension, or receiving concomitant drugs known to lower blood pressure.1
• Monitor for hepatotoxicity more closely in patients with preexisting liver dysfunction or who are co-infected with hepatitis B virus (HBV) and/or hepatitis C virus C (HCV).1
• Closely monitor for evidence of infections during treatment with maraviroc.1
• Closely monitor for maraviroc-associated adverse events in patients with moderate hepatic impairment who receive maraviroc 150 mg with a potent cytochrome P-450 (CYP) isoenzyme 3A inhibitor.1

Administration

Maraviroc is available as oral tablets and an oral solution.1 Administer maraviroc orally twice daily without regard to food.1 Administer maraviroc in combination with other antiretroviral agents.1

Swallow maraviroc tablets whole; do not chew.1 Assess children for the ability to swallow tablets; use the oral solution instead of tablets in those unable to reliably swallow tablets.1

Administer maraviroc oral solution containing 100 mg/5 mL using the press-in bottle adapter and appropriate oral dosing syringe supplied by the manufacturer; use the 3-mL oral syringe for doses ≤2.5 mL and the 10-mL oral syringe for doses >2.5 mL.1 Exercise care when measuring neonate doses due to the small volumes of oral solution required.1 Consult the manufacturer's instructions for more specific information regarding administration of the oral solution.1

Store maraviroc tablets and oral solution at 20-25ºC (excursions permitted to 15-30ºC).1 Discard any unused oral solution 60 days after first opening the bottle.1

Dosage

Dosage of maraviroc is based on different concomitant drugs.1

Adult Dosage

Treatment of HIV-1 Infection in Adults Receiving a Potent CYP3A Inhibitor (with or without a CYP3A Inducer)

For the treatment of HIV-1 infection in adults receiving concomitant therapy with a drug that is a potent inhibitor of CYP3A, with or without a potent CYP3A inducer , the recommended dosage of maraviroc is 150 mg twice daily.1 Potent CYP3A inhibitors include protease inhibitors (except ritonavir-boosted tipranavir), cobicistat, ritonavir-boosted elvitegravir, nefazodone, ketoconazole, itraconazole, and clarithromycin.1

Treatment of HIV-1 Infection in Adults Receiving Noninteracting Drugs (Drugs that are not CYP3A Inhibitors or Inducers)

For the treatment of HIV-1 infection in adults receiving concomitant therapy with noninteracting drugs (all drugs that are not potent CYP3A inhibitors or inducers, such as ritonavir-boosted tipranavir, nevirapine, nucleoside reverse transcriptase inhibitors [NRTIs], enfuvirtide, dolutegravir, and raltegravir), the recommended dosage of maraviroc is 300 mg twice daily.1

Treatment of HIV-1 Infection in Adults Receiving Potent and Moderate CYP3A Inducers (without a Potent CYP3A Inhibitor)

For the treatment of HIV-1 infection in adults receiving concomitant therapy with potent and moderate CYP3A inducers , without a potent CYP3A inhibitor, the recommended dosage of maraviroc is 600 mg twice daily.1 Potent and moderate CYP3A inducers include efavirenz, etravirine, rifampin, carbamazepine, phenobarbital, and phenytoin.1

Postexposure Prophylaxis following Occupational Exposure to HIV

For postexposure prophylaxis of HIV infection following occupational exposure† (PEP) in health-care personnel or other individuals, the recommended dosage of maraviroc is 300 mg twice daily, provided the patient is not receiving a potent CYP3A inducer or inhibitor.199 Use maraviroc in conjunction with other antiretrovirals.199

Initiate the PEP regimen as soon as possible following occupational exposure to HIV (preferably within hours) and continue for 4 weeks, if tolerated.199

Pediatric Dosage

The recommended dosage of maraviroc in pediatric patients is based on weight and should not exceed the recommended adult dosage.1 The recommended dosage also differs based on concomitant medications.1

There are insufficient data to recommend use of maraviroc in pediatric patients receiving potent and moderate CYP3A inducers (without a potent CYP3A inhibitor) including efavirenz, etravirine, rifampin, carbamazepine, phenobarbital, and phenytoin.1

Treatment of HIV-1 Infection with Oral Tablets

The recommended dosage of maraviroc tablets for the treatment of HIV-1 infection in pediatric patients ≥2 years of age weighing ≥10 kg is outlined in Table 1.1

^aPotent CYP3A inhibitors (with or without a CYP3A inducer) including: protease inhibitors (except ritonavir-boosted tipranavir), cobicistat, ritonavir-boosted elvitegravir, nefazodone, ketoconazole, itraconazole, and clarithromycin.

^bNoninteracting concomitant drugs including all drugs that are not potent CYP3A inhibitors or inducers, such as: ritonavir-boosted tipranavir, nevirapine, all NRTIs, enfuvirtide, dolutegravir, and raltegravir.

Treatment of HIV-1 Infection with Oral Solution

The recommended dosage of maraviroc oral solution for the treatment of HIV-1 infection in pediatric patients weighing ≥2 kg is outlined in Table 2.

^aPotent CYP3A inhibitors (with or without a CYP3A inducer) including: protease inhibitors (except ritonavir-boosted tipranavir), cobicistat, ritonavir-boosted elvitegravir, nefazodone, ketoconazole, itraconazole, and clarithromycin.

^bNoninteracting concomitant drugs including all drugs that are not potent CYP3A inhibitors or inducers, such as: ritonavir-boosted tipranavir, nevirapine, all NRTIs, enfuvirtide, dolutegravir, and raltegravir.

Special Populations

Hepatic Impairment

The manufacturer makes no specific dosage recommendations for patients with hepatic impairment.1 Maraviroc plasma concentrations may be increased when administered to patients with hepatic impairment.1

Renal Impairment

Dosage adjustments for adults with renal impairment are outlined in Table 3.1

^aPotent CYP3A inhibitors (with or without a CYP3A inducer) including: protease inhibitors (except ritonavir-boosted tipranavir), cobicistat, ritonavir-boosted elvitegravir, nefazodone, ketoconazole, itraconazole, and clarithromycin.

^bNoninteracting concomitant drugs including all drugs that are not potent CYP3A inhibitors or inducers, such as: ritonavir-boosted tipranavir, nevirapine, all NRTIs, enfuvirtide, dolutegravir, and raltegravir.

^cPotent and moderate CYP3A inducers (without a potent CYP3A inhibitor) including: efavirenz, etravirine, rifampin, carbamazepine, phenobarbital, and phenytoin.

There are no data to recommend dosage adjustments in pediatric patients with mild or moderate renal impairment.1 Maraviroc is contraindicated in pediatric patients with severe renal impairment or with end-stage renal disease on regular hemodialysis who are receiving potent CYP3A inhibitors or inducers.1

Geriatric Patients

The manufacturer makes no specific dosage recommendations for maraviroc in geriatric patients, but recommends caution because of possible age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.1

Contraindications

Patients with severe renal impairment (creatinine clearance <30 mL/minute) or end-stage renal disease (ESRD) who are receiving concomitant therapy with a potent cytochrome P-450 (CYP) isoenzyme 3A inhibitor or inducer.1

Warnings/Precautions

Warnings

Hepatotoxicity

The prescribing information for maraviroc contains a boxed warning regarding the risk of hepatotoxicity.1 Hepatotoxicity may be preceded by severe rash or signs of a systemic allergic reaction (e.g., fever, eosinophilia, elevated immunoglobulin E [IgE] antibody levels).1 These effects have occurred approximately 1 month after initiation of maraviroc.1 Hepatitis has been reported in the absence of allergic features and in patients without preexisting hepatic disease.1

Perform appropriate laboratory testing (e.g., ALT, AST, bilirubin) prior to initiation of maraviroc therapy and as clinically indicated during therapy with the drug.1 Immediately evaluate patients who develop rash or signs or symptoms of hepatitis or allergic reaction.1 Consider discontinuance of maraviroc in any patient with manifestations of hepatitis or with increased liver transaminases and a rash or other systemic symptoms.1

Safety and efficacy of maraviroc have not been specifically studied in patients with clinically important underlying liver disease.1 If maraviroc is used in patients with preexisting liver dysfunction or in those with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, additional monitoring may be necessary.1

Other Warnings and Precautions

Severe Skin and Hypersensitivity Reactions

Severe, potentially life-threatening skin and hypersensitivity reactions have been reported in those receiving maraviroc, usually in those receiving concomitant therapy with other drugs associated with such reactions.1 Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug rash with eosinophilia and systemic symptoms (DRESS) have been reported;1 these cases usually involved rash, constitutional findings, and sometimes organ dysfunction, including hepatic failure.1

Discontinue maraviroc and other suspected agents immediately if signs or symptoms of severe skin or hypersensitivity reactions occur (e.g., severe rash or rash accompanied by fever, malaise, muscle or joint aches, blisters, oral lesions, conjunctivitis, facial edema, lip swelling, and/or eosinophilia).1 Life-threatening reactions could occur if discontinuance of maraviroc or other suspect agents is delayed after the onset of rash.1

Monitor clinical status, including liver aminotransferases, and initiate appropriate therapy.1

Cardiovascular Effects

Cardiovascular events (including myocardial ischemia and/or myocardial infarction) have been reported in patients receiving maraviroc during clinical studies.1 Patients who experienced these events generally had cardiac disease or risk factors for cardiac disease prior to initiation of maraviroc; the contribution of maraviroc to these events is not known.1

Symptomatic postural hypotension was observed in healthy individuals receiving higher than recommended dosages of maraviroc in early studies.1 In clinical studies in patients with human immunodeficiency virus type 1 (HIV-1) infection, the incidence of postural hypotension in those receiving the recommended dosage of maraviroc was similar to that in patients receiving placebo.1

Patients with cardiovascular comorbidities or risk factors for postural hypotension and patients receiving concomitant therapy with drugs with hypotensive effects could be at increased risk of adverse cardiovascular events triggered by postural hypotension.1 Additional monitoring may be warranted in such patients.1

In addition, patients with severe renal insufficiency or with end-stage renal disease (ESRD) may be at increased risk of postural hypotension because of increased maraviroc concentrations.1

Immune Reconstitution Syndrome

During initial treatment, HIV-infected patients whose immune systems respond to antiretroviral therapy may develop an inflammatory response to indolent or residual opportunistic infections (e.g., Mycobacterium avium , M. tuberculosis , cytomegalovirus, Pneumocystis jirovecii , herpes simplex virus, varicella-zoster virus); such responses may necessitate further evaluation and treatment.1

Autoimmune disorders (e.g., Graves' disease, polymyositis, Guillain-Barré syndrome) have also been reported to occur in the setting of immune reconstitution; however, the time to onset is more variable and can occur many months after initiation of antiretroviral therapy.1

Infection

Because some immune cells have CC chemokine receptor 5 (CCR5) receptors, the possibility exists that agents that bind to CCR5 receptors, including maraviroc, can increase the risk of infection.1 In phase 3 clinical studies, the overall incidence and severity of infection (including acquired immunodeficiency syndrome [AIDS]-defining category C infections) in antiretroviral-experienced patients receiving maraviroc was similar to that in patients receiving placebo.1 AIDS-defining category C events also were reported in antiretroviral-naive patients.1 In studies that evaluated maraviroc in antiretroviral-experienced patients, upper respiratory tract infections or pneumonia occurred in 23 or 2%, respectively, of those receiving maraviroc and in 13 or 5%, respectively, of those receiving placebo.1 Herpes infections were reported more frequently in those receiving maraviroc than in those receiving placebo.1

Monitor for infection in patients receiving maraviroc.1

Malignancy

Because some immune cells have CCR5 receptors, the possibility exists that agents that bind to CCR5 receptors, including maraviroc, can increase the risk of malignancy.1 No increase in the incidence of malignancy in maraviroc-treated patients has been observed to date.1 Long-term studies are needed to fully assess this risk.1

Coreceptor Tropism Assay

CC chemokine receptor 5 (CCR5) tropism testing with a highly sensitive tropism assay is required for appropriate use of maraviroc.1 Some experts also recommend that such testing be considered in patients who exhibit virologic failure while receiving a CCR5 antagonist.200

Specific Populations

Pregnancy

The Antiretroviral Pregnancy Registry (APR) monitors pregnancy outcomes in women exposed to maraviroc during pregnancy.1 Clinicians are encouraged to register patients in the APR by calling 800-258-4263 or visiting [Web].1,202

There are limited data on the use of maraviroc in pregnant women.1 In animal studies, no evidence of adverse developmental outcomes was observed in rats or rabbits with maraviroc systemic exposures that were approximately 20 or 5 times higher, respectively, than systemic exposures in humans at recommended dosages.1

In a study in 18 pregnant women receiving maraviroc (150 or 300 mg twice daily) in conjunction with other antiretrovirals, overall maraviroc exposures were 28-30% lower during the third trimester of pregnancy compared with postpartum exposures.23 Limited amounts of maraviroc were distributed across the placenta (median cord blood to maternal blood concentration ratio was 0.33).23

In the clinical trial evaluating maraviroc pharmacokinetics in HIV-1-exposed neonates (born to HIV-1 infected mothers) from birth to 6 weeks of age, exposure to maternal efavirenz in utero (for ≥2 weeks immediately prior to delivery) did not have a meaningful impact on maraviroc pharmacokinetics.1

Lactation

Maraviroc is distributed into milk in rats.1 It is not known whether maraviroc is distributed into human milk, affects human milk production, or affects the breast-fed infant.1

Because of the risk of adverse effects in the infant and the risk of HIV transmission, HIV-infected women should not breast-feed infants.1,202

In the clinical trial evaluating maraviroc pharmacokinetics in HIV-1-exposed neonates (born to HIV-1 infected mothers) from birth to 6 weeks of age, exposure to maternal efavirenz during breast-feeding did not have a meaningful impact on maraviroc pharmacokinetics.1

Pediatric Use

The safety and efficacy of maraviroc have been established in pediatric patients from birth to <18 years of age.1 The use of maraviroc in pediatric patients was supported by pharmacokinetic and safety data in pediatric patients and by previous demonstration of efficacy in adult patients.1

A multicenter clinical trial evaluated the safety, antiviral activity, and pharmacokinetics of maraviroc in treatment-experienced, CCR5-tropic, HIV-1-infected pediatric patients 2 to <18 years of age weighing ≥10 kg.1 The pharmacokinetics of maraviroc in those receiving potent CYP3A inhibitors (with or without a potent CYP3A inducer) were similar to those observed in adults.1 There are limited clinical pharmacokinetic data in pediatric patients 2 to <18 years of age receiving noninteracting concomitant drugs.1 Based on population pharmacokinetic modeling and simulation, the recommended dosing regimen of maraviroc for this population is predicted to result in similar maraviroc exposures as seen in adults receiving maraviroc 300 mg twice daily with noninteracting concomitant drugs.1

No clinical trials or pharmacokinetic data are available in children 6 weeks to <2 years of age.1 Maraviroc dosing recommendations in these patients when they are concomitantly receiving noninteracting drugs are solely based on population pharmacokinetic modeling and simulation.1

A clinical trial evaluated the safety and pharmacokinetics of maraviroc in HIV-1-exposed neonates (born to HIV-1 infected mothers) who weighed ≥2 kg at birth; ages ranged from birth to 6 weeks.1 Pharmacokinetic parameters were similar to those in adults.1 Exposure to maternal efavirenz in utero (for ≥2 weeks immediately prior to delivery) did not have a meaningful impact on maraviroc pharmacokinetics.1

There are insufficient data to make dosage recommendations for the use of maraviroc in pediatric patients weighing <10 kg and concomitantly receiving drugs that are CYP3A inhibitors, or in any pediatric patient receiving a potent CYP3A inducer (efavirenz, etravirine, rifampin, carbamazepine, phenobarbital, or phenytoin) without a potent CYP3A inhibitor.1

Maraviroc is not recommended in pre-term neonates or in pediatric patients weighing <2 kg.1

Geriatric Use

Experience in patients ≥65 years of age is insufficient to determine whether they respond differently than younger adults.1

Use maraviroc with caution in geriatric patients because of age-related decreases in hepatic and renal function and potential for concomitant disease and drug therapy.1

Maraviroc pharmacokinetics have not been fully assessed in patients ≥65 years of age.1

Hepatic Impairment

Peak plasma concentrations and area under the plasma concentration-time curve (AUC) are higher in individuals with mild or moderate hepatic impairment compared with individuals with normal hepatic function.1 The pharmacokinetics of maraviroc have not been investigated in adults with severe hepatic impairment or in pediatric patients with any degree of hepatic impairment.1

Use maraviroc with caution in patients with hepatic impairment and in those coinfected with HBV or HCV.1 Safety and efficacy of maraviroc have not been specifically studied in patients with clinically important underlying liver disorders.1 In clinical studies in antiretroviral-experienced HIV-infected patients, approximately 6% were coinfected with HBV and 6% were coinfected with HCV.1 Because of these small numbers of patients, no conclusions can be made regarding whether coinfection with HBV or HCV increases the risk for maraviroc-associated adverse hepatic effects.1

Closely monitor for maraviroc-associated adverse effects in individuals with moderate hepatic impairment receiving maraviroc 150 mg twice daily and a drug that strongly inhibits CYP3A.1

Renal Impairment

Maraviroc is contraindicated in adults with severe renal impairment (creatinine clearance <30 mL/minute) or with ESRD on regular hemodialysis who are receiving concomitant therapy with a drug that is a potent inhibitor or inducer of CYP3A.1

Use maraviroc in adults with severe renal impairment or ESRD only if they are not receiving concomitant therapy with a potent CYP3A inhibitor or inducer and only when no alternative treatment options are available.1 If adults with severe renal impairment or ESRD experience any symptoms of postural hypotension while receiving maraviroc 300 mg twice daily, reduce the dosage of the drug to 150 mg twice daily.1

Pharmacokinetics of maraviroc in adults with mild or moderate renal impairment are similar to those in adults with normal renal function.1

Maraviroc has not been studied in pediatric patients with renal impairment.1 There are insufficient data to recommend a maraviroc dosage in pediatric patients with mild or moderate renal impairment.1 Maraviroc is contraindicated in pediatric patients with severe renal impairment or with ESRD on regular hemodialysis who are receiving a potent CYP3A inhibitor or inducer.1

Common Adverse Effects

The most common adverse effects (incidence >8%) reported in antiretroviral-experienced adults that occurred at a higher frequency compared with placebo are upper respiratory tract infections, cough, pyrexia, rash, and dizziness.1

The most common adverse effects (incidence >8%) reported in treatment-naïve adults that occurred at a higher frequency than the comparator(s) are upper respiratory tract infections, bronchitis, flatulence, bloating and distention, upper respiratory tract signs and symptoms, and GI atonic and hypomotility disorders.1

The most common adverse effects (incidence ≥3%) reported in treatment-experienced pediatric patients are vomiting, abdominal pain, diarrhea, nausea, and dizziness.1 In the study in neonates birth to 6 weeks of age, the most common adverse effect reported with maraviroc was decreased hemoglobin.1 No additional adverse reactions were observed in these neonates compared with those seen in adults.1

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Maraviroc is metabolized by the cytochrome P-450 (CYP) isoenzyme 3A, and the possibility exists that drugs that inhibit or induce this isoenzyme may alter the pharmacokinetics of maraviroc.1

In vitro studies indicate that maraviroc does not inhibit CYP isoenzymes 1A2, 2B6, 2C8, 2C9, 2C19, or 3A.1 Pharmacokinetic interaction is unlikely with drugs that are substrates for these isoenzymes.1

Maraviroc does not induce CYP1A2.1 Maraviroc may inhibit CYP2D6 at higher than recommended dosage.1

Drugs Affecting or Affected by P-glycoprotein Transport

Maraviroc is a substrate of the P-glycoprotein (P-gp) transport system, and the possibility exists that drugs that are inhibitors or inducers of this system may alter the pharmacokinetics of maraviroc.1

Although in vitro studies suggest that maraviroc could inhibit P-gp in the gut, in vivo studies using digoxin indicate that maraviroc may not inhibit or induce P-gp to any clinically important extent.1

Drugs Affecting or Affected by Organic Anion Transporters

Maraviroc is a substrate for organic anion transporter polypeptide (OATP) 1B1, and drugs that are inhibitors of OATP1B1 may alter the pharmacokinetics of maraviroc.1 Dosage adjustment may be required when maraviroc is coadministered with those drugs.1

Maraviroc is unlikely to inhibit the uptake of OATP1B1.1

Maraviroc is not a substrate for, and does not inhibit, organic anion transporter (OAT) 1, OAT3, organic cation transporter (OCT) 2, novel organic cation transporter (OCTN) 1, or OCTN2 at clinically important concentrations.1

Drugs Affecting or Affected by Multidrug Resistance-associated Protein

Maraviroc is a substrate for multidrug resistance-associated protein (MRP) 2, and drugs that are inhibitors of MRP2 may alter the pharmacokinetics of maraviroc.1 Dosage adjustment may be required when maraviroc is coadministered with those drugs.1

Maraviroc is unlikely to inhibit the export of MRP2.1

Anticonvulsants

Carbamazepine, phenobarbital, and phenytoin are potent CYP3A and/or P-gp inducers, and are expected to decrease maraviroc concentrations; however, these interactions have not been studied.1 Recommended adult dosage of maraviroc is 600 mg twice daily in patients receiving these anticonvulsants, provided the regimen does not include a potent CYP3A inhibitor.1

Antifungal Agents

Itraconazole

Possible pharmacokinetic interaction exists with itraconazole, a potent CYP3A inhibitor.1

If itraconazole and maraviroc are used concomitantly, the recommended dosage of maraviroc in adults is 150 mg twice daily.1

Ketoconazole

Pharmacokinetic interaction exists with ketoconazole, a potent CYP3A inhibitor (substantially increased maraviroc plasma concentrations and AUC).1

If ketoconazole and maraviroc are used concomitantly, the recommended dosage of maraviroc in adults is 150 mg twice daily.1

Rifampin

Pharmacokinetic interaction exists with rifampin (decreased maraviroc plasma concentrations).1,22

If rifampin is used concomitantly with maraviroc, the recommended dosage of maraviroc in adults is 600 mg twice daily, provided the regimen does not include a potent CYP3A inhibitor.1

Antiretroviral Agents

HIV Entry and Fusion Inhibitors

Enfuvirtide

When maraviroc is used in conjunction with enfuvirtide in a regimen that does not include a potent CYP3A inhibitor or inducer, the recommended dosage of maraviroc in adults is 300 mg twice daily.1

There is no in vitro evidence of antagonistic antiretroviral effects between maraviroc and enfuvirtide.1

HIV Integrase Inhibitors (INSTIs)

Dolutegravir

If maraviroc is used in conjunction with dolutegravir, the recommended maraviroc dosage in adults is 300 mg twice daily.1

Elvitegravir

Pharmacokinetic interaction exists with ritonavir-boosted elvitegravir (increased maraviroc plasma concentrations).1

If maraviroc is used in conjunction with ritonavir-boosted elvitegravir, the recommended maraviroc dosage in adults is 150 mg twice daily.1

Raltegravir

Pharmacokinetic interaction exists with raltegravir (decreased raltegravir plasma concentrations and AUC, which is not clinically important).1

If maraviroc is used in conjunction with raltegravir in a regimen that does not include a potent CYP3A inhibitor or inducer, the recommended maraviroc dosage in adults is 300 mg twice daily.1

HIV Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs)

There is no in vitro evidence of antagonistic antiretroviral effects between maraviroc and HIV NNRTIs (efavirenz, nevirapine).1

Efavirenz

Pharmacokinetic interaction exists with efavirenz (decreased maraviroc plasma concentrations and AUC).1,22 The recommended dosage of maraviroc in adults is 600 mg twice daily in patients receiving efavirenz, provided the regimen does not include a potent CYP3A inhibitor.1

Etravirine

Pharmacokinetic interaction exists with etravirine (decreased maraviroc plasma concentrations and AUC).1

If maraviroc and etravirine are used concomitantly, the recommended maraviroc dosage in adults is 600 mg twice daily, provided the regimen does not include a potent CYP3A inhibitor.1

Nevirapine

If nevirapine is used with maraviroc, the recommended maraviroc dosage in adults is 300 mg twice daily.1

HIV Nucleoside and Nucleotide Reverse Transcriptase Inhibitors (NRTIs)

There is no in vitro evidence of antagonistic antiretroviral effects between maraviroc and NRTIs (abacavir, didanosine, emtricitabine, lamivudine, stavudine, tenofovir, zidovudine).1

Maraviroc has no clinically important effect on the pharmacokinetics of lamivudine or zidovudine.1

Tenofovir does not affect the pharmacokinetics of maraviroc.1

When maraviroc is used concomitantly with HIV NRTIs (abacavir, didanosine, emtricitabine, lamivudine, stavudine, tenofovir, zidovudine), the recommended dosage of maraviroc in adults is 300 mg twice daily, provided the regimen does not include a potent CYP3A inhibitor or inducer.1

HIV Protease Inhibitors (PIs)

There is no in vitro evidence of antagonistic antiretroviral effects between maraviroc and HIV PIs (amprenavir, atazanavir, darunavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, tipranavir).1

Atazanavir

Pharmacokinetic interaction exists with ritonavir-boosted or unboosted atazanavir (increased maraviroc plasma concentrations and AUC).1

Recommended dosage of maraviroc in adults is 150 mg twice daily in patients receiving atazanavir.1

Darunavir

Pharmacokinetic interaction exists with ritonavir-boosted darunavir (increased maraviroc plasma concentrations and AUC).1

Recommended dosage of maraviroc in adults is 150 mg twice daily in patients receiving darunavir.1

Fosamprenavir

Pharmacokinetic interaction exists with maraviroc (increased plasma concentrations and AUC of maraviroc; decreased plasma concentrations and AUC of amprenavir [active metabolite of fosamprenavir]).1

No dosage adjustments are necessary when a maraviroc dosage of 150 mg twice daily is used concomitantly with ritonavir-boosted fosamprenavir dosed once or twice daily.1 Administer fosamprenavir with ritonavir when used concomitantly with maraviroc.1

Lopinavir

Pharmacokinetic interaction exists with the fixed combination of lopinavir and ritonavir (lopinavir/ritonavir) (substantially increased maraviroc plasma concentrations and AUC).1,22

The recommended dosage of maraviroc in adults is 150 mg twice daily in patients receiving lopinavir/ritonavir.1

Nelfinavir

The recommended dosage of maraviroc in adults is 150 mg twice daily in patients receiving nelfinavir.1

Ritonavir

Pharmacokinetic interaction exists with low-dose ritonavir (increased maraviroc plasma concentrations and AUC).1

The recommended dosage of maraviroc in adults is 150 mg twice daily in patients receiving regimens that include low-dose ritonavir (except ritonavir-boosted tipranavir).1

Saquinavir

Pharmacokinetic interaction exists with ritonavir-boosted saquinavir (increased maraviroc plasma concentrations and AUC).1

The recommended dosage of maraviroc in adults is 150 mg twice daily in patients receiving ritonavir-boosted saquinavir.1

Tipranavir

There is no clinically important effect on maraviroc pharmacokinetics with ritonavir-boosted tipranavir.1

The recommended dosage of maraviroc in adults is 300 mg twice daily in patients receiving ritonavir-boosted tipranavir, provided the regimen does not include a potent CYP3A inhibitor or inducer.1

Cobicistat

Pharmacokinetic interaction exists with cobicistat (increased maraviroc plasma concentrations).1

If maraviroc is used in conjunction with cobicistat, the recommended maraviroc dosage in adults is 150 mg twice daily.1

Co-trimoxazole

Co-trimoxazole does not affect the pharmacokinetics of maraviroc.1

Estrogens and Progestins

Maraviroc does not have any clinically important effects on the pharmacokinetics of oral contraceptives containing ethinyl estradiol and levonorgestrel.1

Clarithromycin

Possible pharmacokinetic interaction exists with clarithromycin, a strong CYP3A4 inhibitor (increased maraviroc plasma concentrations).1

The recommended dosage of maraviroc in adults is 150 mg twice daily in patients receiving clarithromycin.1

Midazolam

Pharmacokinetic interaction is unlikely with midazolam.1

Nefazodone

Possible pharmacokinetic interaction exists with nefazodone.1 Recommended dosage of maraviroc is 150 mg twice daily in patients receiving nefazodone.1

St. John's Wort

Pharmacokinetic interaction exists with St. John's wort ( Hypericum perforatum ) (substantially decreased maraviroc concentrations); potential for loss of virologic response and possible resistance to maraviroc.1 Concomitant use is not recommended.1

Description

Maraviroc, a synthetic antiretroviral agent, is a human immunodeficiency virus (HIV) entry inhibitor.1,6,8,200 The drug is a small-molecule CC chemokine receptor 5 (CCR5) antagonist.1,6,8,200

HIV enters host cells by attaching to the CD4⁺ T-cell receptor using 1 of 2 chemokine coreceptors, CCR5 or CXC chemokine receptor 4 (CXCR4).7,8 Maraviroc selectively binds to CCR5 on the cell membrane and prevents the interaction of HIV type 1 (HIV-1) glycoprotein 120 and CCR5 necessary for CCR5-tropic HIV-1 to enter cells.1,6 Maraviroc does not inhibit entry of CXCR4-tropic and dual/mixed-tropic HIV-1 into cells.1 CCR5 is a coreceptor for the most commonly transmitted HIV-1 strains that predominate during the early stages of infection; 6,200 this form remains the dominant form in many patients with late-stage infection.6 Maraviroc also may be active against some HIV-2 isolates; however, no approved assays to determine HIV-2 coreceptor tropism exist and HIV-2 is known to use many other minor coreceptors in addition to CCR5 and CXCR4.200

Maraviroc is active against some strains of HIV-1 resistant to HIV nucleoside reverse transcriptase inhibitors (NRTIs), HIV nonnucleoside reverse transcriptase inhibitors (NNRTIs), HIV protease inhibitors (PIs), and HIV entry and fusion inhibitors (enfuvirtide).1 HIV-1 strains with reduced susceptibility to maraviroc have been produced in vitro and have emerged during maraviroc therapy.1

Following single oral doses of maraviroc 1-1200 mg in uninfected subjects, peak plasma concentrations are attained in 0.5-4 hours; maraviroc pharmacokinetics are not dose proportional over the dose range.1 The absolute bioavailability of a 100-mg oral dose is 23%; the absolute bioavailability of a 300-mg dose is predicted to be 33%.1 Maraviroc is a substrate for the efflux transporter P-glycoprotein (P-gp).1 The AUC and peak plasma concentration decreased by 33% when a 300-mg tablet was administered with a high-fat meal, and AUC decreased by 73% when 75 mg of the oral solution was administered with a high- fat meal in healthy adult volunteers.1

Maraviroc is approximately 76% bound to human plasma proteins.1 The drug is principally metabolized by cytochrome P-450 (CYP) isoenzyme 3A to inactive metabolites; CYP2C9, CYP2D6, and CYP2C19 do not contribute significantly to the metabolism of maraviroc.1 Approximately 20% of a dose is eliminated in urine (8% as unchanged maraviroc) and 76% of a dose is excreted in feces (25% as unchanged maraviroc).1 The terminal half-life of maraviroc is 14-18 hours.1

Based on population pharmacokinetic analyses, age did not have a clinically important effect on maraviroc exposure in patients ≤65 years of age.1 Based on population pharmacokinetics and 2 clinical CYP3A5 genotype analyses for race, no dosage adjustment of maraviroc is recommended based on race or gender.1

Advice to Patients

• Inform patients about the critical nature of compliance with HIV therapy and of remaining under the care of a clinician.1 Inform patients to take their antiretroviral regimen as prescribed; do not alter or discontinue the antiretroviral regimen without consulting a clinician.1
• Inform patients that maraviroc is used in conjunction with other antiretrovirals and is not for monotherapy.1
• If a dose of maraviroc is missed, instruct patients to take the dose as soon as possible and to take the next dose at the regularly scheduled time.1 Do not double the next dose or take more than the prescribed dose.1
• Advise patients that liver problems, including life-threatening reactions, have occurred.1 Advise patients to inform their clinician if they have underlying hepatitis B or C infection or elevations in liver laboratory tests prior to starting therapy.1 Advise patients to immediately discontinue maraviroc and seek medical attention if signs or symptoms of hepatitis or allergic reactions (rash, yellow skin or eyes, dark urine, vomiting, abdominal pain) occur.1 Inform patients that their clinician will order laboratory tests for liver enzymes and bilirubin prior to starting maraviroc, at certain times during treatment, and if they develop severe rash or signs and symptoms of hepatitis or an allergic reaction during treatment.1
• Advise patients with cardiovascular comorbidities, a history of postural hypertension, or receiving drugs known to lower blood pressure that they may be at increased risk for cardiovascular events.1 Advise patients to avoid driving a motor vehicle or operating hazardous machinery if they experience dizziness while taking maraviroc.1
• Advise women to inform their clinician if they are or plan to become pregnant.1 Inform patients that there is a pregnancy registry that monitors outcomes in women exposed to maraviroc during pregnancy.1
• Advise women to inform their clinician if they plan to breastfeed.1 Advise HIV-infected women not to breastfeed.1
• Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal products (e.g., St. John's wort), and any concomitant illnesses.1
• Advise patients of other important precautionary information.1

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

1. ViiV Healthcare. Selzentry^® (maraviroc) tablets and oral solution prescribing information. Durham, NC; 2022 Sep.

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6. Dorr P, Westby M, Dobbs S et al. Maraviroc (UK-427,857), a potent, orally bioavailable, and selective small-molecule inhibitor of chemokine receptor CCR5 with broad-spectrum anti-human immunodeficiency virus type 1 activity. Antimicrob Agents Chemother . 2005; 49:4721-32. [PubMed 16251317]

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8. Lederman MM, Penn-Nicholson A, Cho M et al. Biology of CCR5 and its role in HIV infection and treatment. JAMA . 2006; 296:815-26. [PubMed 16905787]

15. Cooper DA, Heera J, Goodrich J et al. Maraviroc versus efavirenz, both in combination with zidovudine-lamivudine, for the treatment of antiretroviral-naive subjects with CCR5-tropic HIV-1 infection. J Infect Dis . 2010; 201:803-13. [PubMed 20151839]

17. Gulick RM, Lalezari J, Goodrich J et al. Maraviroc for previously treated patients with R5 HIV-1 infection. N Engl J Med . 2008; 359:1429-41. [PubMed 18832244]

18. Sierra-Madero J, Di Perri G, Wood R et al. Efficacy and safety of maraviroc versus efavirenz, both with zidovudine/lamivudine: 96-week results from the MERIT study. HIV Clin Trials . 2010 May-Jun; 11:125-32.

22. Abel S, Jenkins TM, Whitlock LA et al. Effects of CYP3A4 inducers with and without CYP3A4 inhibitors on the pharmacokinetics of maraviroc in healthy volunteers. Br J Clin Pharmacol . 2008; 65(Suppl 1):38-46. [PubMed 18333864]

23. Colbers A, Best B, Schalkwijk S et al. Maraviroc Pharmacokinetics in HIV-1-Infected Pregnant Women. Clin Infect Dis . 2015; 61:1582-9. [PubMed 26202768]

24. Giaquinto C, Mawela MP, Chokephaibulkit K et al. Pharmacokinetics, Safety, and Efficacy of Maraviroc in Treatment-Experienced Pediatric Patients Infected With CCR5-Tropic HIV-1. Pediatr Infect Dis J. 2018;37(5):459-465.

198. Centers for Disease Control and Prevention. Updated guidelines for antiretroviral postexposure prophylaxis after sexual, injection drug use, or other nonoccupational exposure to HIV - United States, 2016. From HHS AIDS Information (AIDSinfo) website. [Web]

199. Kuhar DT, Henderson DK, Struble KA et al. Updated US Public Health Service guidelines for the management of occupational exposures to human immunodeficiency virus and recommendations for postexposure prophylaxis. Infect Control Hosp Epidemiol . 2013; 34:875-92. [PubMed 23917901]

200. Panel on Antiretroviral Guidelines for Adults and Adolescents, US Department of Health and Human Services (HHS). Guidelines for the use of antiretroviral agents in HIV-1-infected adultsand adolescents (March 23, 2023). Updates may be available at HHS AIDS Information (AIDSinfo) website. [Web]

201. Panel on Antiretroviral Therapy and Medical Management of HIV-infected Children, US Department of Health and Human Services (HHS). Guidelines for the use of antiretroviral agents in pediatric HIV infection (January 31, 2023). Updates may be available at HHS AIDS Information (AIDSinfo) website. [Web]

202. Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission, US Department of Health and Human Services (HHS). Recommendations for use of antiretroviral drugs in pregnant HIV-1-infected women for maternal health and interventions to reduce perinatal HIV transmission in the United States (January 31, 2023). Updates may be available at HHS AIDS Information (AIDSinfo) website. [Web]

300. Hardy W, Gulick R, Mayer H, et al. Two-year safety and virologic efficacy of maraviroc in treatment-experienced patients with CCR5-tropic HIV-1 infection: 96 -week combined analysis of MOTIVATE 1 and 2. J Acquir Immune Defic Syndr. 2010;55(5):558-564.