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Efficacy and Tolerability of Maraviroc for Children With Antiretroviral Experience
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7th IAS Conference on HIV Pathogenesis, Treatment and Prevention, June 30-July 3, 2013, Kuala Lumpur
Mark Mascolini
Half of 94 antiretroviral-experienced children in an 8-country study of twice-daily maraviroc had a week-48 viral load below 400 copies, and 40% had a load below 48 copies [1]. Poor adherence often explained virologic failure, which was more frequent in adolescents than in younger children.
To date, the Study A4001031 analysis involves 94 children who took at least one dose of study medication by March 12, 2013. Researchers split children into four cohorts by age and formulation: cohort 1, 2 to under 6, liquid; cohort 2, 6 to under 12 tablet; cohort 3, 6 to under 12, liquid; and cohort 4, 12 to under 18, tablet. Stage 1 of the study involved intensive pharmacokinetic analysis. Stage 1 children continued to Stage 2 once researchers determined they were taking an appropriate dose. Study countries were Brazil, Italy, Portugal, Puerto Rico, South Africa, Spain, Thailand, and the United States.
All study participants had CCR5-using HIV-1, a viral load above 1000 copies, and experience with at least two antiretroviral classes. All children were either off treatment or taking a stable antiretroviral regimen for more than 4 weeks before their screening visit. Background regimens selected with the help of resistance testing included three or more antiretrovirals. The investigators based the maraviroc dose on body surface area and CYP3A4 inhibition or induction with comedications. Doses ranged from 40 to 600 mg twice daily.
Cohort 1 included 13 children, cohort 2 included 27, cohort 3 included 12, and cohort 4 included 42. Respective median body surface areas, in meters squared, were 0.7, 1.0, 0.9, and 1.3, and respective median ages were 3, 10, 9, and 14. All median baseline viral loads lay at or above 4.3 log10 copies/mL (about 20,000 copies). Median treatment durations were 226 days in cohort 1, 526 days in cohort 2, 240 days in cohort 3, and 261 days in cohort 4.
In the four cohorts, 1, 4, 3, and 18 children discontinued before week 48. There were no virologic failures in cohort 1, 3 in cohort 2, 2 in cohort 3, and 11 in cohort 4. Numbers of children in the four cohorts who completed week 48 were 5 (38%), 19 (70%), 5 (42%), and 20 (48%).
In a missing/discontinuation-equals-failure analysis, 67% had a viral load below 400 copies at week 24 and 52% were below that mark at week 48. Numbers with a sub-400-copy load at week 48 were 4 of 6 in cohort 1, 15 of 23 in cohort 2, 5 of 8 in cohort 3, and 15 of 38 in cohort 4. In the same type of analysis, 46% had a viral load below 48 copies at week 24, as did 40% at week 48. Numbers with a sub-48-copy load at week 48 were 3 of 6 in cohort 1, 10 of 23 in cohort 2, 4 of 8 in cohort 3, and 13 of 38 in cohort 4. Virologic failure was usually associated with nonadherence, which is a particular problem in adolescents across the world. Median CD4 percent in every cohort rose through 48 weeks.
Sixteen children (17%) had a serious adverse event, 10 (10.6%) had a grade 3 or 4 adverse event, and 3 (3.2%) discontinued because of adverse events. The most frequent adverse events were infection and infestations in 49% and gastrointestinal disorders in 36%. Other frequent adverse events were nervous system disorders in 14%, reproductive system and breast disorders in 13%, and skin and subcutaneous tissue disorders in 12%.
Enrollment is ongoing and follow-up will continue through 5 years.
Reference
1. Giaquinto C, Keet L, Fortuny C, et al. Safety and efficacy of maraviroc in CCR5-tropic HIV-1-infected children aged 2 to < 18 years. 7th IAS Conference on HIV Pathogenesis, Treatment and Prevention, June 30-July 3, 2013, Kuala Lumpur. Abstract MOAB0103.
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