Off-label use of maraviroc in HIV-1-infected paediatric patients in clinical practice

Abstract

Maraviroc (MVC) is not approved for HIV-1-infected paediatric patients. This is the first assessment of the use of MVC-based salvage therapy in vertically HIV-1-infected paediatric patients in clinical settings. The results suggest that MVC-based salvage therapy is useful in children and adolescents with extensive resistance profile leading to maintained virological suppression in up to 88% of the patients with CCR5-tropic virus. The likelihood of treatment success might increase when MVC is combined with other active drugs.

Next-generation sequencing provides an added value in determining drug resistance and viral tropism in Cameroonian HIV-1 vertically infected children

“…[ 38 , 39 ] Further investigations might help in establishing novel public health strategies for an eventual usage of maraviroc in children. [ 18 , 40 ] As current PMTCT-practice might not be an independent factor for viral-tropism (i.e., similar distribution in X4-variants irrespective of PMTCT-history), CCR5-antagonist (maraviroc) could be a useful therapeutic weapon for pediatric HAART. [ 15 , 18 , 40 ]…”

Off‐licence use of once‐daily maraviroc in children and adolescents with perinatally acquired HIV‐1 infection

“…Regarding efficacy, of the 14 children who were viraemic at the start of MVC ART, 86% ever achieved virological suppression, with two-thirds remaining suppressed at a median of 104 weeks, comparable to response rates seen in treatment-experienced adults, in the single reported study of the off-label use of twice-daily MVC in adolescents and within the interim analysis of the ongoing paediatric study MVC A4001031 [3,5,6,10]. Of those who switched to MVC ART while on suppressive ART, all remained suppressed after a median of 156 weeks.…”

“…MVC is currently unlicensed for use in children despite its approval for treatment-experienced adults in 2007, almost a decade ago. Off-licence use of MVC has occurred in a small number of children and adolescents but to date only twice-daily use has been described [6].…”

“…While phase 2 safety and efficacy studies of twice-daily MVC in treatment-experienced children aged 2-17 years are ongoing (A4001031), prior offlicence paediatric use has occurred as a consequence of HIV-1-associated resistance mutations limiting ART options, ART toxicity, and for simplification to once-daily regimens in adolescents struggling with adherence [4,5]. In the single previous reported study of the paediatric use of MVC in salvage therapy (n = 20), all patients received MVC twice daily [6]. In the vast majority of perinatally infected infants, the transmitted strain utilizes the C-C chemokine receptor type 5 (CCR5) coreceptor with the subsequent emergence of X4 virus [7].…”

HIV-1 subtype C predicted co-receptor tropism in Africa: an individual sequence level meta-analysis

“…However, as disease progresses, CXCR4 utilizing viruses emerge in about 50% of infected individual [41][42][43]. By Variation at the GPGQ Crown motif (%) 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 and large, in Africa Maraviroc is prescribed mostly for patients who have failed first and second line regimens, which are comprised of nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, and protease inhibitors [44,45]. Since, HIV-1-C drives the epidemic in Southern Africa and accounts for about 46% of infections worldwide [24], the current investigation was aimed at determining the distribution of R5 and X4 viruses in early versus chronic infections in HIV-1-C acquired through MTCT and heterosexual routes in Africa.…”