Pierre Frange1,2,3, Véronique Avettand-Fenoel2,4, Florence Veber1, Stéphane Blanche1,5, Marie-Laure Chaix6,7. 1. Unité d'Immunologie, Hématologie et Rhumatologie pédiatriques, AP-HP, Hôpital universitaire Necker - Enfants malades, Paris, France. 2. Laboratoire de Microbiologie clinique, AP-HP, Hôpital universitaire Necker - Enfants malades, Paris, France. 3. EA7328, Université Paris Descartes, Sorbonne Paris Cité, Paris, France. 4. EA7327, Université Paris Descartes, Sorbonne Paris Cité, Paris, France. 5. EA7323, Université Paris Descartes, Sorbonne Paris Cité, Paris, France. 6. Laboratoire de Virologie, AP-HP, Hôpital Saint Louis, Paris, France. 7. INSERM U941 Université Paris Diderot, Paris, France.
Abstract
Objectives: To describe the prevalence of transmitted drug resistance (TDR) among 84 children newly diagnosed with HIV in France in 2006-17. Methods: HIV-1 resistance-associated mutations (RAMs) were characterized using both the 2009 Stanford list of mutations and the 2017 French National Agency for AIDS Research (ANRS) algorithm. A genotypic susceptibility score (GSS) was estimated for each first-line recommended ART combination. Results: Patients were mainly infected through mother-to-child transmission (MTCT) (73/84; 86.9%), but only 18 children (24.7% of vertically infected patients) were previously exposed to antiretroviral prophylaxis from MTCT. Non-B variants were identified in 90.5% (76/84) of patients. The frequency of TDR was 8.3% (7/84) using the 2009 Stanford list and 16.7% (14/84) using both the Stanford list and the 2017 ANRS algorithm. The prevalence of PI-, NRTI-, efavirenz/nevirapine-, etravirine/rilpivirine- and doravirine-associated RAMs was 0%, 3.6%, 6.0%, 11.9% and 2.4%, respectively. Single-, dual- and triple-class resistance was present in 15.5%, 1.2% and 0% of cases, respectively. Additionally, 3/60 (5%) strains had integrase inhibitor (INI)-related RAMs (an isolated E157Q mutation, which could mostly affect the susceptibility to raltegravir/elvitegravir rather than that to dolutegravir). Among the 18 children exposed to MTCT prophylaxis, RAMs were identified in only 1 case (5.6%). The proportion of fully active combinations (GSS = 3) was ≥97.6%, ≥94.1%, ≥92.9% and ≥89.3% for PI-, INI-, efavirenz/nevirapine- and rilpivirine-based regimens, respectively. Conclusions: The proportion of NRTI- and NNRTI-related TDR in children is lower in France than in low- and middle-income countries. However, we suggest favouring PI- or dolutegravir- over NNRTI-based combinations to treat newly diagnosed HIV-infected children, even in the absence of previous exposure to antiretroviral prophylaxis of MTCT.
Objectives: To describe the prevalence of transmitted drug resistance (TDR) among 84 children newly diagnosed with HIV in France in 2006-17. Methods:HIV-1 resistance-associated mutations (RAMs) were characterized using both the 2009 Stanford list of mutations and the 2017 French National Agency for AIDS Research (ANRS) algorithm. A genotypic susceptibility score (GSS) was estimated for each first-line recommended ART combination. Results:Patients were mainly infected through mother-to-child transmission (MTCT) (73/84; 86.9%), but only 18 children (24.7% of vertically infectedpatients) were previously exposed to antiretroviral prophylaxis from MTCT. Non-B variants were identified in 90.5% (76/84) of patients. The frequency of TDR was 8.3% (7/84) using the 2009 Stanford list and 16.7% (14/84) using both the Stanford list and the 2017 ANRS algorithm. The prevalence of PI-, NRTI-, efavirenz/nevirapine-, etravirine/rilpivirine- and doravirine-associated RAMs was 0%, 3.6%, 6.0%, 11.9% and 2.4%, respectively. Single-, dual- and triple-class resistance was present in 15.5%, 1.2% and 0% of cases, respectively. Additionally, 3/60 (5%) strains had integrase inhibitor (INI)-related RAMs (an isolated E157Q mutation, which could mostly affect the susceptibility to raltegravir/elvitegravir rather than that to dolutegravir). Among the 18 children exposed to MTCT prophylaxis, RAMs were identified in only 1 case (5.6%). The proportion of fully active combinations (GSS = 3) was ≥97.6%, ≥94.1%, ≥92.9% and ≥89.3% for PI-, INI-, efavirenz/nevirapine- and rilpivirine-based regimens, respectively. Conclusions: The proportion of NRTI- and NNRTI-related TDR in children is lower in France than in low- and middle-income countries. However, we suggest favouring PI- or dolutegravir- over NNRTI-based combinations to treat newly diagnosed HIV-infectedchildren, even in the absence of previous exposure to antiretroviral prophylaxis of MTCT.
Authors: Kevin Melody; Chandra N Roy; Christopher Kline; Mackenzie L Cottrell; Dwayne Evans; Kathleen Shutt; Pleuni S Pennings; Brandon F Keele; Moses Bility; Angela D M Kashuba; Zandrea Ambrose Journal: J Virol Date: 2020-03-31 Impact factor: 6.549