ena-STUDY-Hopital Europeen Georges Pompidou-18-11-2018-19:40:31:495-118
Integrase inhibitors in African children
Background. The expanded drug resistance mutations (DRMs) to the current WHO recommended 1st- and 2nd- line pediatric combined antiretroviral therapy (cART) in sub-Saharan Africa make these regimens no longer sufficient to care HIV-infected children. We herein investigate the predictive efficacy of integrase (IN) strand transfer inhibitors (INSTI) in INSTI-naive HIV-infected children and adolescents in virological failure living in the Central African Republic.Methods. Plasma was collected from 18 children (n=8) and adolescents (n=10) in virological failure (i.e. viral load > 1,000 copies/mL) after 5 years of 1st- and/or 2nd- line cART, attending the Complexe Pédiatrique of Bangui. IN, reverse transcriptase (RT) and protease (P) genes were genotyped and DRMs to INSTIs, nucleoside reverse transcriptase inhibitors (NRTIs), non-NRTI (NNRTI) and protease inhibitors (PI), were interpreted using the Stanford University algorithm.Results. Successful IN, RT and P genotypes were obtained for 18, 14 and 15 children (median, 11 years, range: 5-18; 8 females) respectively. Two (2/18; 11.2%) viruses from children under first-line regimen harbored INSTI DRMs at the codon 138 (E138K and E138T) known to harbor major resistance mutations with accessory mutations L74I, G140K, G140R and G163R. Polymorphic mutations in IN gene were frequently observed. The majority (16/18; 88.8%) of HIV-1 IN sequences demonstrated full sensitivity for all major INSTIs with a large frequency of natural polymorphism mutations. Most (12/15; 80%) genotyped viruses harbored at least 1 major DRM conferring a resistance to at least one of the WHO-recommended antiretroviral drugs (NNRTIs, NRTIs and PIs) prescribed in 1st- and 2nd-line regimen.Conclusions. These observations demonstrate that INSTIs could be proposed in 1st- line regimen in the majority of African children or adolescents and that, INSTIs may constitute relevant therapeutic alternatives as 2nd- and 3rd- line cART regimens in pediatric HIV infection in the African setting.
Background. The expanded drug resistance mutations (DRMs) to the current WHO recommended 1st- and 2nd- line pediatric combined antiretroviral therapy (cART) in sub-Saharan Africa make these regimens no longer sufficient to care HIV-infected children. We herein investigate the predictive efficacy of integrase (IN) strand transfer inhibitors (INSTI) in INSTI-naive HIV-infected children and adolescents in virological failure living in the Central African Republic.Methods. Plasma was collected from 18 children (n=8) and adolescents (n=10) in virological failure (i.e. viral load > 1,000 copies/mL) after 5 years of 1st- and/or 2nd- line cART, attending the Complexe Pédiatrique of Bangui. IN, reverse transcriptase (RT) and protease (P) genes were genotyped and DRMs to INSTIs, nucleoside reverse transcriptase inhibitors (NRTIs), non-NRTI (NNRTI) and protease inhibitors (PI), were interpreted using the Stanford University algorithm.Results. Successful IN, RT and P genotypes were obtained for 18, 14 and 15 children (median, 11 years, range: 5-18; 8 females) respectively. Two (2/18; 11.2%) viruses from children under first-line regimen harbored INSTI DRMs at the codon 138 (E138K and E138T) known to harbor major resistance mutations with accessory mutations L74I, G140K, G140R and G163R. Polymorphic mutations in IN gene were frequently observed. The majority (16/18; 88.8%) of HIV-1 IN sequences demonstrated full sensitivity for all major INSTIs with a large frequency of natural polymorphism mutations. Most (12/15; 80%) genotyped viruses harbored at least 1 major DRM conferring a resistance to at least one of the WHO-recommended antiretroviral drugs (NNRTIs, NRTIs and PIs) prescribed in 1st- and 2nd-line regimen.Conclusions. These observations demonstrate that INSTIs could be proposed in 1st- line regimen in the majority of African children or adolescents and that, INSTIs may constitute relevant therapeutic alternatives as 2nd- and 3rd- line cART regimens in pediatric HIV infection in the African setting.