Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection
The information in the brief version is excerpted directly from the full-text guidelines. The brief version is a compilation of the tables and boxed recommendations.
Entry and Fusion Inhibitors
Last Updated: April 14, 2020; Last Reviewed: April 14, 2020
|Maraviroc (MVC, Selzentry)|
Oral Solution: 20 mg/mL
Tablets: 25 mg, 75 mg, 150 mg, 300 mg
|Dosing Recommendations||Selected Adverse Events|
|Neonate and Infant Dose:
- Absorption: Absorption of maraviroc (MVC) is slightly reduced with ingestion of a high-fat meal. There were no food restrictions in the adult trials (which used the tablet formulation) or in the pediatric trial (which used both the tablet and oral solution formulations) that demonstrated the efficacy, antiviral activity, and safety of MVC. Therefore, MVC can be given with or without food.
- Metabolism: MVC is a cytochrome P450 (CYP) 3A and p-glycoprotein (P-gp) substrate and requires dose adjustments when administered with medications that modulate CYP3A or P-gp. A patient’s medication profile should be carefully reviewed for potential drug interactions before MVC is administered; recommended MVC doses are based on concomitant medications and their anticipated effect on MVC metabolism.
- More common: Cough, fever, upper respiratory tract infections, rash, musculoskeletal symptoms, abdominal pain, vomiting, diarrhea, and headache. Dizziness occurred in 12.2% of adults but only 3.2% of children when MVC was administered twice daily.
- Less common (more severe): Hepatotoxicity has been reported; some cases were preceded by evidence of a systemic allergic reaction (including pruritic rash, eosinophilia, or elevated levels of immunoglobulin). Serious adverse events (AEs) occurred in <2% of MVC-treated adult patients and included cardiovascular abnormalities (e.g., angina, heart failure, myocardial infarction), hepatic cirrhosis or failure, cholestatic jaundice, viral meningitis, pneumonia, myositis, osteonecrosis, and rhabdomyolysis.
An HIV tropism assay should be performed before MVC is administered to a patient. Clinical failure may also represent the outgrowth of CXCR4-using (naturally resistant) HIV variants.
MVC is approved by the Food and Drug Administration for use in treatment-experienced children aged ≥2 years and weighing ≥10 kg who have CCR5-tropic HIV-1.1 A study of MVC dosing in neonates and infants is currently underway (ClinicalTrials.gov identifier NCT02778204). Preliminary data have been presented.2
Pharmacokinetics and Efficacy
The pharmacokinetics, safety, and efficacy of MVC were examined in an international dose-finding and efficacy study (A4001031) that involved treatment-experienced children aged 2 years to <18 years and weighing ≥10 kg who had plasma HIV RNA >1,000 copies/mL. Fifty-one percent of the 103 children who participated in the study had HIV-1 subtype C, 25% had subtype B, and 23% had other subtypes.
In this trial, the MVC dose was based on body surface area and the composition of the patient’s optimized background therapy. Most participants (90 of 103 participants, or 87%) received MVC in combination with potent CYP3A inhibitors, while 10 participants received MVC with noninteracting medications and only three participants received MVC with CYP3A inducers (without CYP3A inhibitors). The key pharmacologic target (geometric mean Caverage of >100 ng/mL) was achieved with both the tablet and oral solution formulations of MVC.3
From a mean baseline plasma HIV RNA concentration of 4.4 log10 copies/mL, a decrease of ≥1.5 log10 occurred in all four age-based cohorts. Only two participants discontinued the study due to AEs. The most common MVC-related AEs through 48 weeks were diarrhea (which occurred in 20.3% of participants), vomiting (19.8%), and upper respiratory infections (16.2%). At Week 48, 48% of participants had HIV RNA <48 copies/mL.3 The absolute CD4 T lymphocyte cell count and percentage increased in all four subgroups of the study, with overall median increases of 192 cells/mm3 (interquartile range [IQR] 92–352 cells/mm3) and 4% (IQR 1% to 8%), respectively.
- Maraviroc [package insert]. Food and Drug Administration. 2018. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/022128s018,208984s001lbl.pdf.
- Rosebush JC, Best B, Chadwick E, et al. Maraviroc safety & pharmacokinetics in HIV-exposed neonates. Abstract 842. Presented at: Conference on Retroviruses and Opportunistic Infections. 2020. Boston, Massachusetts. Available at: https://www.croiconference.org/abstract/maraviroc-safety-pharmacokinetics-in-hiv-exposed-neonates/.
- 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. Available at: https://www.ncbi.nlm.nih.gov/pubmed/29023357.