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MEDMAL-4222; No. of Pages 5 ARTICLE IN PRESS

Médecine et maladies infectieuses xxx (2019) xxx–xxx

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Original article

High rates of antiretroviral coverage and virological suppression in

HIV-1-infected children and adolescents
Taux élevés de couverture thérapeutique antirétrovirale et de succès virologique
chez les enfants et adolescents vivant avec le VIH-1
A. Soumah a, V. Avettand-Fenoel b,c, F. Veber a, D. Moshous a,d, N. Mahlaoui a,d,e,
S. Blanche a,f, P. Frange a,b,∗,g
a
Unité d’immunologie, hématologie et rhumatologie pédiatrique, hôpital Necker–Enfants malades, AP–HP, 149, rue de Sèvres, 75015 Paris, France
b
Laboratoire de microbiologie clinique, hôpital Necker–Enfants malades, AP–HP, 149, rue de Sèvres, 75015 Paris, France
c
CNRS 8104/Inserm U1016, institut Cochin, université Paris Descartes, 22, rue Méchain, 75014 Paris, France
d
Inserm UMR1163, institut Imagine, Sorbonne Paris Cité, université Paris Descartes, 24, boulevard du Montparnasse, 75015 Paris, France
e
Centre de référence des déficits immunitaires héréditaires (CEREDIH), hôpital Necker–Enfants malades, AP–HP, 149, rue de Sèvres, 75015 Paris, France
f
EA7323, Sorbonne Paris Cité, université Paris Descartes, 12, rue de l’École de médecine, 75006 Paris, France
g
EHU 7328, institut Imagine, Sorbonne Paris Cité, université Paris Descartes, 149, rue de Sèvres, 75015 Paris, France

article info abstract

Article history: Objectives. – To assess the outcome of HIV-infected individuals attending one of the largest French
Received 13 March 2019 pediatric HIV centers in 2016–2017 and to compare the rates of antiretroviral coverage and virological
Received in revised form 6 April 2019 suppression with the UNAIDS targets.
Accepted 9 October 2019
Patients and methods. – The clinical and immuno-virological status of 163 HIV-1-infected children and
Available online xxx
adolescents attending Necker Hospital in Paris, France, were investigated. Virological suppression was
defined as an HIV-1 viral load < 50 copies/mL for at least six months. All genotypic resistance tests
Keywords:
performed since birth were analyzed.
Children
Results. – Most patients were born in Sub-Saharan African countries (41.7%) or in France (38.0%). Their
Antiretroviral resistance
HIV median age was 14 years [IQR 7.3–17.0]. Although 33.7% of individuals had a history of AIDS-defining
UNAIDS clinical event(s), 86.5% of children/adolescents were free from HIV-related symptoms at their most recent
Virological success evaluation. Antiretroviral coverage was high (98.2%; mainly including one integrase inhibitor [42.3%] or
one protease inhibitor [23.9%]). At the last visit, most patients (82.8%) had normal CD4 T lymphocytes
counts (≥ 25%). Although 61.7% of antiretroviral-experienced children had resistance to ≥ 1 drug class
and 9.2% had triple-class resistance, 80.3% of patients receiving antiretrovirals for ≥ 6 months (126/157)
were virologically suppressed. International adoptees were more frequently virologically suppressed
than other patients (96.0% versus 74.6%, P = 0.02).
Conclusions. – Antiretroviral coverage exceeded the second UNAIDS 90 target aimed at ending the AIDS
epidemic. The rate of virological suppression, one of the highest reported in children in high-income
countries, is approaching the third UNAIDS 90 target and the rate observed in French HIV-infected adults
on antiretrovirals.
© 2019 Elsevier Masson SAS. All rights reserved.

résumé

Mots clés : Objectifs. – Évaluer l’état de santé des patients vivant avec le VIH suivis dans l’un des principaux centres
Enfants pédiatriques franc¸ais et comparer les taux de couverture antirétrovirale et de succès virologique aux
ONUSIDA objectifs de l’ONUSIDA (≥ 90 %).
Résistance aux antirétroviraux Patients et méthodes. – Nous décrivons le statut clinique et immuno-virologique de 163 enfants et adoles-
Succès virologique
cents vivant avec le VIH-1 suivis à l’hôpital Necker (Paris, France) en 2016–2017. Le succès virologique
VIH
était défini par une virémie VIH-1 < 50 copies/ml depuis au moins 6 mois.

Preliminary results of this study were presented at the 9th International Francophone Conference on HIV & viral hepatitis (AFRAVIH; Bordeaux, France – April 4–7, 2018).
∗ Corresponding author: Laboratoire de microbiologie clinique, hôpital Necker–Enfants malades, AP–HP, 149, rue de Sèvres, 75015 Paris, France.
E-mail address: pierre.frange@aphp.fr (P. Frange).

https://doi.org/10.1016/j.medmal.2019.10.006
0399-077X/© 2019 Elsevier Masson SAS. All rights reserved.

Please cite this article in press as: Soumah A, et al. High rates of antiretroviral coverage and virological suppression in HIV-1-infected
children and adolescents. Med Mal Infect (2019), https://doi.org/10.1016/j.medmal.2019.10.006
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2 A. Soumah et al. / Médecine et maladies infectieuses xxx (2019) xxx–xxx

Résultats. – L’âge médian des patients était de 14 ans [intervalle interquartile: 7,3–17,0]. Bien qu’un antécé-
dent d’évènement(s) clinique(s) classant sida était retrouvé chez 33,7 % des enfants/adolescents, 86,5 % des
patients ne présentaient pas de symptômes liés au VIH à la dernière visite. La couverture antirétrovirale
était élevée (98,2 %, incluant principalement un inhibiteur d’intégrase [42,3 %] ou de protéase [23,9 %]).
À la dernière visite, 82,8 % avaient un taux de lymphocytes T CD4 normal. Malgré des taux élevés de
résistance à ≥ 1 (61,7 %) et à 3 (9,2 %) classes d’antirétroviraux, 80,3 % des enfants/adolescents traités
depuis ≥ 6 mois étaient en succès virologique. Les enfants faisant l’objet d’une adoption internationale
étaient plus fréquemment en succès virologique que les autres patients (96,0 % contre 74,6 %, p = 0,02).
Conclusions. – La couverture antirétrovirale dépassait le second objectif de l’ONUSIDA. Le succès
virologique, l’un des plus élevés décrits dans les pays développés, approchait le troisième objectif de
l’ONUSIDA et celui observé en France chez les adultes traités par antirétroviraux.
© 2019 Elsevier Masson SAS. Tous droits réservés.

1. Introduction
Thanks to the almost systematic use of highly active antiretro-
viral therapy (HAART), HIV infection in children and adolescents
has become a chronic disease in high-income countries. However,
achieving and maintaining good compliance with treatment and
viral suppression in the long-term remains challenging in children
perinatally infected with HIV [1]. A previous study of 210 ado-
lescents born in France before 1993 reported viral load (VL) < 50
copies/mL in only 43% of adolescents and 54.5% of those receiving
HAART [2]. More recent studies reported higher rates of virolog-
ical suppression in children/adolescents in high-income countries
[3–5]. However, these rates often remained below the third UNAIDS
90 target aiming at 90% of people on HAART with viral suppression
by 2020 [6].
We investigated the clinical and immunovirological status of
all HIV-1-infected children and adolescents attending the largest
French pediatric HIV center (Necker Hospital) from June 2016 to
February 2017.
2. Patients and methods
The present research was conducted in accordance with the
Declaration of Helsinki and national and institutional standards.
Parents/guardians provided informed consent for the anonymous
use of their children’s clinical and biological data for biomedical
research. Patients diagnosed with HIV infection before 13 years of
age were included in the French Pediatric ANRS EPF-CO10 Cohort
(for those aged < 18 years) and the French ANRS CO19-COVERTE
Cohort (for those aged 18 to 25 years), which were approved by the
Cochin Hospital Ethics Committee.
Information collected included demographic (age, sex, birth
country, living conditions, schooling/occupational status), clinical
data (history of AIDS-defining clinical events, current clinical symp-
toms, current antiretroviral regimen), and laboratory data (HIV-1
VL at the last visit and during the six previous months, lymphocytes
CD4 T cell counts). Virological suppression was defined as an HIV-1
VL < 50 copies/mL for at least six months.
All genotypic resistance tests performed since birth were ana-
lyzed. HIV-1 resistance-associated mutations (RAMs) were defined
using both the 2009 Stanford RAMs list for nucleotide reverse tran-
scriptase inhibitors (NRTI), first-generation non-NRTI (NNRTI), and
protease inhibitors (PI), and the 2017 French Agency for Research
on AIDS and Viral Hepatitis (French acronym ANRS) algorithm v27
(www.hivfrenchresistance.org) for etravirine, rilpivirine, and inte-
grase inhibitors (INI), as previously described [7].
Chi2 tests or Fisher’s exact tests were used to compare discrete
variables, and the Wilcoxon rank test was used to compare contin-
uous variables between patients with virological suppression and
those with detectable viremia. Analyses were performed with SAS
9.4 (SAS Inst., Cary, NC, USA).
3. Results
A total of 163 HIV-1-infected patients were enrolled. Their
median age was 14 years [interquartile range: 7.3–17.0]. Most of
them had been infected through mother-to-child HIV transmission
(96.9%) and were born in Sub-Saharan African countries (41.7%)
or in France (38.0%) (Table 1). Twenty-five children (15.3%) were
international adoptees, mainly from South-East Asian countries
(Vietnam and Thailand; 84.0%).
3.1. Living conditions
Most individuals were living with family members (71.2%), were
attending school with academic success, or were attending voca-
tional training (125/163, 76.7%). Five infants were preschoolers
and eight adolescents had a job. Only 25 individuals (15.3%) were
attending school with academic failure or required special educa-
tion.
3.2. Clinical evaluations
Around one third of patients had a history of AIDS-defining
clinical event(s). However, most children (72.4%) were cur-
rently asymptomatic. Twenty-two of the 45 patients with clinical
symptoms presented with non-progressive sequelae of HIV-
related clinical events, mainly neurological sequelae of HIV-related
encephalopathy (15/22, 68.2%) and/or bronchiectasis due to past
recurrent bronchopulmonary infections (6/22, 27.3%).
3.3. Treatment and RAMs
All but three patients (98.2%) were receiving HAART. Two chil-
dren, diagnosed with HIV at the age of 6 and 9 years respectively,
were free of HAART since birth because of a status of long-term
nonprogressors. Both of them were asymptomatic since birth and
presented at the last evaluation with normal CD4 T lymphocytes
counts (40% and 34%, respectively) and moderate HIV viremia (4.1
and 3.4 log10 copies/mL, respectively). The remaining adolescent
had completely stopped HAART several months before. At the
last evaluation, this 19-year-old patient was asymptomatic and
presented with moderate immune deficiency (CD4 T lymphocytes
count = 23%) and low level of HIV viremia (2.5 log10 copies/mL).
The genotypic resistance tests performed since birth were
analyzed in 120/161 antiretroviral-experienced patients.
The prevalence of PI-, NRTI-, efavirenz/nevirapine-, and
etravirine/rilpivirine-related RAMs was 12.5%, 42.5%, 27.5%,
and 20.8%. Viruses with single, dual, and triple class resistance

Please cite this article in press as: Soumah A, et al. High rates of antiretroviral coverage and virological suppression in HIV-1-infected
children and adolescents. Med Mal Infect (2019), https://doi.org/10.1016/j.medmal.2019.10.006
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Table 1
Characteristics of 163 HIV-1-infected children and adolescents attending Necker Hospital (Paris, France) in 2016–2017, and statistical analysis of factors associated with
virological suppression.
Caractéristiques de 163 enfants et adolescents infectés par le VIH-1 pris en charge à l’hôpital Necker (Paris, France) de 2016 à 2017, et analyse statistique des facteurs associés à la
suppression virologique.

All Virologically-suppressed Patients with detectable P

(N = 163) patientsa (N = 127) viremia (N = 36)

Male sex (N, %) 89 (54.6) 70 (55.1) 19 (52.8) 0.85

Age (years) (N, %) 0.46
0–11 60 (36.8) 49 (38.6) 11 (30.6)
12–17 65 (39.9) 51 (40.2) 14 (38.9)
≥ 18 38 (23.3) 27 (21.2) 11 (30.6)
Country of birth 0.02
France 62 (38.0) 46 (36.2) 16 (44.4)
Sub-Saharan African country 68 (41.7) 49 (38.6) 19 (52.8)
Asian country 22 (13.5) 21 (16.5) 1 (2.8)
Other countryb 11 (6.7) 11 (8.7) 0 (0.0)
Guardians/caregivers 0.02
At least one biological parent 107 (65.6) 82 (64.6) 25 (69.4)
Other family member 9 (5.5) 5 (3.9) 4 (11.1)
Adoptive parents (international adoption) 25 (15.3) 24 (18.9) 1 (2.8)
Institutional caregivers (orphans) 8 (4.9) 6 (4.7) 2 (5.6)
Autonomous life (young adults) 14 (8.6) 10 (7.9) 4 (11.1)
Schooling/occupational status (N, %) 0.55
Pre-schooling age 5 (3.1) 3 (2.4) 2 (5.6)
General schooling/vocational training with academic 133 (81.6) 105 (82.7) 28 (77.8)
success or employment
Schooling with academic failurec or special education 25 (15.3) 19 (14.9) 6 (16.7)
History of AIDS-defining clinical event (N, %) 55 (33.7) 46 (36.2) 9 (25.0) 0.24
Current clinical status (N, %) 0.87
Absence of clinical symptoms 118 (72.4) 93 (73.2) 25 (69.4)
Sequelae of past HIV-related clinical events 22 (13.5) 17 (13.4) 5 (13.9)
Severe bronchiectasis 6 (3.7) 5 (3.9) 1 (2.8)
Blindness (post-cytomegalovirus retinitis) 2 (1.2) 2 (1.6) 0 (0.0)
Neurological sequelae of HIV encephalopathy 15 (9.2) 13 (10.2) 2 (5.6)
Ischemic extremities (post-pneumococcal meningitis) 1 (0.6) 1 (0.8) 0 (0.0)
Growth retardation 5 (3.1) 2 (1.6) 3 (8.3)
Clinical symptoms unrelated to HIVd 23 (14.1) 17 (13.4) 6 (16.7)
Current antiretroviral treatment (N, %) 0.12
2 NRTIs + 1 INIe 69 (42.3) 58 (45.3) 11 (30.6)
2 NRTIs + 1 PIf 39 (23.9) 27 (21.1) 12 (33.3)
2 NRTIs + 1 NNRTIg 32 (19.6) 28 (21.9) 4 (11.1)
Other antiretroviral combinations 20 (12.2) 14 (11.7) 6 (16.7)
None 3 (1.8) 0 (0.0) 3 (8.3)
Current T CD4 lymphocytes count (N, %) < 0.001
≥ 25% 135 (82.8) 120 (94.5) 15 (41.7)
15–24% 25 (15.3) 7 (5.5) 18 (50.0)
< 15% 3 (1.8) 0 (0) (8.3)

NRTI: nucleotide reverse transcriptase inhibitor; NNRTI: non-NRTI; PI: protease inhibitor; INI: integrase inhibitor.
a
Virological suppression was defined as HIV-1 viremia < 50 copies/mL maintained for more than six months.
b
European countries (N = 8), USA (N = 1), Haiti (N = 1), Morocco (N = 1).
c
Includes children who repeated two or more grades or dropped out of school.
d
Neurobehavioral sequelae of fetal drug exposure, autism, congenital blindness, sickle cell disease, beta-thalassemia major, congenital cardiopathy, overweight, chronic
eczema, severe allergic keratoconjunctivitis.
e
Mainly dolutegravir (65/69, 94.2%).
f
Mainly darunavir/ritonavir (20/39, 51.3%) or lopinavir/ritonavir (16/39, 41.0%).
g
Mainly nevirapine (18/32, 56.3%) or rilpivirine (10/32, 31.3%).

were isolated in 25.8%, 26.7%, and 9.2%, respectively. Additionally,
3/87 strains (3.4%) had INI-related RAMs: an isolated E157Q
mutation in two cases and both E92Q and N155H mutations in the
remaining case.
3.4. Immunovirological status
At the last visit, most patients (82.8%) had normal CD4 T lym-
phocytes counts (≥ 25%). During the six months preceding the last
evaluation, HIV viremia was ≥ 1000, ≥ 400, and ≥ 50 copies/mL on
at least one occasion in 23 (14.1%), 27 (16.6%), and 36 children
(22.1%), respectively. Among them, three patients were free from
antiretrovirals and three other children initiated first-line HAART
less than six months before the beginning of the study.
Virological suppression was observed in 77.9% patients
(127/163) and 80.3% of those receiving HAART for > 6 months
(126/157). Virological suppression was more frequently observed
in international adoptees than in other patients (96.0% versus 74.6%,
P = 0.02) and in individuals with CD4 T cell counts ≥ 25% compared
with those with counts < 25% (88.9% versus 25.0%, P < 0.001). Similar
rates of virological suppression were observed between age groups
and between children born in France or in Sub-Saharan African
countries.
4. Discussion
We reported the outcome of 163 patients attending the largest
French pediatric HIV center. Most patients (62.0%) were born out-
side of France, mainly in Sub-Saharan African countries in line with
the drastic decline in mother-to-child HIV-infected infants born
in France. Although around one third of patients had a history of

Please cite this article in press as: Soumah A, et al. High rates of antiretroviral coverage and virological suppression in HIV-1-infected
children and adolescents. Med Mal Infect (2019), https://doi.org/10.1016/j.medmal.2019.10.006
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