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Short Communication
Antiviral Therapy
2021, Vol. 26(6-7-8) 134–140
© The Author(s) 2021
Article reuse guidelines:
sagepub.com/journals-permissions
DOI: 10.1177/13596535211058267
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Comparison of three galenic forms of
lamivudine in young West African children
living with Human Immunodeficiency Virus
Claire Pressiat, PharmD, PhD
1
, Evelyne Dainguy, MD, PhD
2
,
Jean-Marc Tr´
eluyer, MD, PhD
3,4
, Caroline Yonaba, MD
5
, Saik Urien, PhD
3
,
François Eboua, MD
6
, Frantz Foissac, PhD
3
,D
´
esir´
e Lucien Dahourou, MD, PhD
7,8,9
,
Na¨
ım Bouazza, PhD
3
, Karen Malateste
10
, Sophie Desmonde, MD
11
, Alain Pruvost, PhD
12
,
Val´
eriane Leroy, MD, PhD
11,
*, D´
eborah Hirt, Pharm, PhD
3,4,13,
* and
The MONOD ANRS Study Group
†
1
Pharmacology Department, AP-HP, Hˆ
opitaux Universitaires Henri Mondor, Paris Est-Cr´
eteil University, Cr´
eteil, France
2
Pediatric Department, Centre Hospitalier Universitaire of Cocody, Abidjan, Cˆ
ote d’Ivoire
3
Paris Descartes University, Paris, France
4
Clinical Pharmacology Department, AP-HP, Paris Centre Hospital Group, Paris, France
5
Pediatric Department, Centre Hospitalier Universitaire Yalgado Ou´
edraogo, Ouagadougou, Burkina Faso
6
Pediatric Department, Centre Hospitalier Universitaire de Yopougon, Abidjan, C ˆ
ote d’Ivoire
7
MONOD Project, Centre de Recherche Internationale pour la Sant´
e, Ouagadougou, Burkina Faso
8
Centre Muraz, Bobo-Dioulasso, Burkina Faso
9
Institut de Recherche en Sciences de la Sant´
e (IRSS), Ouagadougou, Burkina Faso
10
Inserm, Institut de Recherche pour le D´
eveloppement (IRD), University of Bordeaux, Bordeaux, France
11
Inserm, Unit´
e U1027, CERPOP, Universit´
e Paul Sabatier of Toulouse3, Toulouse, France
12
CEA, INRAE, SPI, Universit´
e Paris Saclay, Gif-sur-Yvette, France
13
Inserm CESP, Hˆ
opital Bicˆ
etre, Le Kremlin-Bicˆ
etre, France
Abstract
Background: Few pharmacokinetic data were reported on dispersible tablets despite their increasing use. One hundred
fifty HIV-infected children receiving lamivudine were enrolled in the MONOD ANRS 12,206 trial. Three galenic forms
were administered: liquid formulation, tablet form and dispersible scored tablet.
Method: HIV-infected children <4 years old were enrolled in the MONOD ANRS 12,206 trial designed to assess the
simplification of a successful 12-months lopinavir-based antiretroviral treatment with efavirenz. Lamivudine plasma
concentrations were analysed using nonlinear mixed effects modelling approach.
Results: One hundred and fifty children (age: 2.5 years (1.9–3.2), weight 11.1 (9.5–12.5) kg (median (IQR)) were included in this
study. Over the study period, 79 received only the syrup form, 29 children switched from syrup form to tablet 3TC/AZT form, 36
from syrup to the orodispersible ABC/3TC form and two from the 3TC/AZT form to the orodispersible ABC/3TC form. The 630
*VL and DH contributed equally to the work.
†
See group composition in the appendix.
Corresponding author:
Claire Pressiat, Pharmacology Department, AP-HP, Hˆ
opitaux Universitaires Henri Mondor, Paris Est-Cr´
eteil University, 1 rue Gustave Eiffel, Cr´
eteil
94010, France.
Email: claire.pressiat@aphp.fr
lamivudine concentrations were best described by a two-compartment model allometrically scaled. Galenic form had no significant
effect on 3TC pharmacokinetic.
Conclusion: This trial provided an opportunity to compare three galenic forms (liquid formulation, tablet form and
dispersible scored tablet) of lamivudine in the target population of young HIV–1-infected children. Galenic form had no
significant effect on lamivudine pharmacokinetics.
Keywords
pharmacokinetics, lamivudine, children, galenic form
Introduction
Immediate initiation of combined antiretroviral therapy (cART)
in all children living with HIV under 2 years of age regardless
of their immune or clinical status has been recommended by the
WHO since 2008.
1
However, the availability of drugs in ap-
propriate formulations remains limited for infants and toddlers.
2
Development of orodispersible fixed dose combinations
(FDCs) has improved adherence, but little is known about the
evaluation of these galenic forms.
Lamivudine (3TC) is used in combination with highly
active antiretroviral therapy for children living with HIV,
available in solid and liquid forms, in single entity and fixed
dose combination products. However, little information is
given on the dosage forms used. Contradictory results were
reported in studies comparing solid and liquid formula-
tions, from no difference to an increase of 55% of the
exposure to 3TC.
3–5
This study allows to compare three
different galenic forms of lamivudine.
Methods
The ANRS 12,206 MONOD randomised trial (see group
composition in appendix 1) was aimed to assess a simplified
once daily cART based on efavirenz versus a twice daily
regimen based on lopinavir/ritonavir among West African
children living with HIVand virologically suppressed after a 12-
month cART based on LPV/r initiated before the age of two.
6
Lamivudine was part of the NRTI regimen used in both
arms. The dosage used was 8 mg/kg/day divided twice
daily into the lopinavir group and once daily into the
efavirenz group. Daily dose regimen was adapted ac-
cording to the treatment strategy, as follows:
Therapeutic education was given systematically by the
assistant pharmacist and the social worker when the drugs
were given to families. Three galenic forms were subse-
quently used over the MONOD trial duration: first, a liquid
formulation (lamivudine 10 mg/mL); then, a tablet form
(3TC/zidovudine [AZT] 30 mg/60 mg Avocomb Kid
®
); last,
a dispersible, scored tablet (Abacavir [ABC]/[3TC] 60 mg/
30 mg produced by Cipla
®
). The dosage used using syrup
formulation was 10 mg/mL (4 mg/kg every 12 h in the
lopinavir group or 8 mg/kg every 24 h in the efavirenz
group), fitting with WHO weight-bands (M6). Then, tablets
or orodispersible fixed dose formulation tablets for ABC-
3TC using WHO weight-bands dosing was done to sub-
stitute for the syrup formulations at M19 and M25. In order
to come as close as possible to the dosage in mg/kg, the
tablets were given either whole or in half a tablet.
Study design and procedures were already published.
7
For the MONOD non-inferiority trial, the statistical pa-
rameter of interest was the difference in viral success rate
12 months after the switch, defined as the rate in the LPV
arm (control) minus the rate in the EFV arm, using a chi-
square test. We aimed to obtain a viral success of at least
76% at 12 months post-switch. We pre-specified that the
margin of the 95% confidence interval of the difference in
the primary outcome between the two arms less than 14%
would meet our criteria for non-inferiority. Based on our
anticipated enrolment of 146 children with 73 children per
arm, we expected an 80% power to detect this difference.
7
The pharmacological data analyses (time, concentra-
tion) have been done with a population approach using the
MONOLIX software.
Pharmacokinetic specific blood sample were scheduled
during the initial cohort phase of the trial at visit M6 and
after that during the randomised simplification phase at
visit M19 and visit M25. The pharmacokinetic parameters
(PK) of each antiretroviral drug received by children have
been measured by one or two blood samples per child
during each visit drawn at two random points in time after
the drug intake. The times of last drug intakes were
recorded precisely to allow an estimation of different
pharmacokinetic parameters. Different time samples were
defined as follows:
- T0, just before taking the drugs;
- T1, 1/2 h at 1:30 after taking;
- T2, 2:30–35 h after taking
- T3, about 8 h after taking.
Plasma 3TC concentrations were determined according to a
validated method. After a simple protein precipitation of 10 μL
of plasma with methanol, the chromatographic separation was
performed using an UPLC coupled to a mass spectrometric
detection MS/MS (Xevo TQ-S from Waters). The analytical
Pressiat et al. 135
column was an Acquity BEH phenyl (1.7 μm, 2.1*50 mm). The
range of quantification was 1–3000 ng/mL. The nonlinear
mixed effect modelling programme MONOLIX 2019R2, with
SAEM algorithm and left censoring of concentrations below the
LOQ was used to analyse the data. One- or two-compartment
structural models, multiplicative, additive or combined residual
variability, and exponential inter-subject variability on
each parameter were tested. An allometric model was
added to represent physiological evolution: P
i
=P
STD
×
(BW
i
/BW
STD
)
PWR
,whereP
STD
is the standard value of
parameter for a patient with the standard body weight
value and P
i
and BW
i
are the parameter and body weight
of the ith individual, allowed to standardise the parameters
estimates for a median weight. From the data, the PWR
(power) exponents could be estimated. However, these
were typically 0.75 for clearance parameters and 1 for
volumes of distribution parameters according to the
theory of the allometric scale. Four covariates have been
tested: sex, age, body-weight and galenic forms. All of the
covariates were tested via an upward model building. A
covariate was selected if (i) its effect was biologically
plausible, (ii) it produced a minimum decrease of 6.63 U
(chi-square test, 1 df, p< 0.01) in the objective function
value (OFV) and (iii) it produced a reduction in the
variability of the pharmacokinetic parameter, assessed by
the associated inter-subject variability. The most signif-
icant covariate of all the covariates tested was added in an
intermediate model. In this intermediate model, all other
covariates were tested and the most significant one was
selected. This process was repeated until no more co-
variate was significant. Models were evaluated thanks to
diagnostic graphics and prediction corrected visual pre-
dictive check.
Results
One hundred and fifty children (77 females and 73 males) and
630 plasma concentrations were available for pharmacokinetic
evaluation. Median [IQR] age was 2.5 years [1.9–3.2] and 11.1
[9.5–12.5] kgs for body-weight. The median lamivudine dose
per day administered was 100 mg, for doses ranging from 50 to
300 mg. Since children were included in the lamivudine study
prior to the lopinavir/efavirenz switch, 142 children received
twice daily and 58 received once daily. Indeed, some children
received a twice daily dose firstandthenaoncedailydoseif
they were randomised to the efavirenz arm.
Out of the 150 children, some have only received a galenic
form: 79 received only the syrup form, two only the tablet 3TC/
AZT form, and two only the orodispersible ABC/3TC form;
others received two dosage forms: thus, 29 children switched
from syrup form to tablet 3TC/AZT form, 36 from the syrup
shape to the orodispersible ABC/3TC form and two from the
3TC/AZT form to the orodispersible ABC/3TC form. No child
received all three dosages forms. Tab le 1 shows the dosages of
3TCusedatM6,M19andM15inthetwoarmsofthetrialasa
function of the dosage form used. The dosage adapted to the
weight was not different between the dosage forms.
A two-compartment model adequately described the
data (Tab le 2 ), with a multiplicative residual variability and
exponential inter-subject variabilities (ISV) on apparent
clearance and central volume of distribution. Interindividual
variability was added on Q/F and Vp/F but this did not improve
Table 1. Median 3TC dose by month, trial arm and dosage form.
Months Syrup AZT/3TC tablet
ABC/3TC
orodispersible form
M6 n 138 2 2
BW (kg) [IQR] 8.5 [7–10.5] 9.2 [9.1–9.3] 9.4 [9.3–9.5]
3TC median dose (mg) [IQR] 45 [45–45] 45 [45–45] 45 [45–45]
M19 Lopinavir arm
n53822
BW (kg) [IQR] 12 [12–13] 12 [11–12] 11.5 [11.25–11.75]
3TC median dose (mg) [IQR] 60 [50–60] 60 [45–60] 45 [45–60]
Efavirenz arm
n33 34
BW (kg) [IQR] 13 [12.5–13.5] 12.5 [11–14.25]
3TC median dose (mg) [IQR] 100 [80–120] 120 [90–120]
M25 Lopinavir arm
n412811
BW (kg) [IQR] 13 [11.5–14] 12 [11.5–13.75] 12.5 [11.7–12.7]
3TC median dose (mg) [IQR] 60 [60–60] 60 [60–60] 60 [45–60]
Efavirenz arm
n6 28
BW (kg) [IQR] 14 [14–14] 13 [12–14]
3TC median dose (mg) [IQR] 105 [92.5–117.5] 120 [120–120]
136 Antiviral Therapy 26(6-8)
the model, thus they were not kept. The allometric scaling of
clearance (CL/F and Q/F) and volume terms (V
c
/F and V
p
/F)
resulted in a 79-U decrease in the objective function value and
improved substantially the goodness of fits plots. Adding an
ISV on a bioavailability fixed to 1, as reference for the syrup
was not significant. Thus, the effects of each form, solid and
dispersible scored tablets were tested as a similar effect on all
apparent clearances and volumes. For both forms, apparent
parameters were increased by less than 10% compared to syrup
and the effect was not significant. Tabl e 1 summarises the final
population pharmacokinetic estimates. PC-VPC that the av-
erage prediction matches the observed concentration time-
courses and that the variability is reasonably estimated
(Figure 1).Thedosageformwasfirst tested as a covariate on
Cl/F and Vc/F. It was not significant. Then, the galenic form
was tested on bioavailability, taking as a reference the syrup
form where the bioavailability was set at 1. Table 3 summarises
median (95% CI) value obtained from the model with an
estimated bioavailability value for each of the three galenic
forms. Since the value 1 (taken as reference for the syrup form)
is included in the two 95% CI of the bioavailability estimates of
the two tablet galenic forms, the three dosage forms were not
statistically different.
Discussion
A two-compartment model with first order absorption and
elimination best described lamivudine pharmacokinetics, as in
previous studies in adults and children.
3,8–11
The apparent
elimination clearance (CL/F= 33 L/h/70 kg) was consistent
with previous adult studies,
13,14
and the effect of body-weight,
here in allometric scale, was also added on lamivudine apparent
clearances and volumes of distribution.
3,4,9,11,12,15,16
This
population model allowed to investigate the effect of three
Figure 1. Prediction-corrected visual-predictive check for lamivudine twice daily (left) and once daily (right). Grey areas represent 95%
CIs of 5th, 50th and 95th simulated percentiles. Lines are empirical (observed) 5th, 50th and 95th percentiles. Circles are the non-
censored, cross the censored observations. Black circles are observations from the syrup form, green circles from the tablet form and
red circles from the orodispersible form.
Phase 1: Therapeutic cohort (for the first year of the trial) M0–M12
Two NRTI among
- ZDV: Syrup 10 mg/mL (4 mg/kg ou 180 mg/m
2
every 12 h) or—ABC: Syrup 20 mg/mL (8 mg/kg every 12 h)
- 3TC: Syrup 10 mg/mL (4mg/kg
®
every 12 h)
- LPV/r: Syrup 80/20 mg/mL (12 mg/kg every 12 h)
Phase 2: Randomised simplification phase (during the second year of the trial) M13-M25
Arm 1: Initial strategy (control group)
- ZDV: Syrup 10 mg/mL (4 mg/kg ou 180 mg/m
2
every 12 h) or—ABC: Syrup 20 mg/mL (8 mg/kg every 12 h)
- 3TC: Syrup 10 mg/mL (4 mg/kg every 12 h)
- LPV/r: Syrup 80/20 mg/mL (12 mg/kg every 12 h)
Arm 2: Once daily simplified strategy
- ABC: Syrup 20 mg/mL (16 mg/kg every morning)
- 3TC: Syrup 10 mg/mL (8 mg/kg every morning)
- EFV: Syrup 30 mg/mL (25 mg/kg every morning on an empty stomach)
Pressiat et al. 137
galenic forms on 3TC pharmacokinetic. Indeed, there are few
pharmacokinetic data on new galenic forms, especially or-
odispersible forms. In order to expand access to treatment for
these children, appropriate drug formulations are required,
particularly the simpler dose combination mini- or scored
tablets preferred by caregivers and children as young as three
years of age.
16
Solid formulations also reduce cost and promote
adherence as compared to solutions, which often require re-
frigeration, have a short shelf-life, often require clean water
(which is not available everywhere), are not easy to store or
transport, and are often complicated for health-care workers to
prescribe and for caregivers to administer.
17
The MONOD trial
provided a unique opportunity to compare three galenic forms
(liquid formulation, tablet form and dispersible scored tablet) of
lamivudine in the target population of young HIV–1-infected
children who were ready to change from liquid formulation to
solid formulations of lamivudine. We showed that the three
galenic forms were not statistically different in terms of
pharmacokinetic properties. These results can be extrapolated
to younger and lighter children because the model is an al-
lometric model. Thus, if we know the weight of each child, this
model can be estimated; however, it should be confirmed by
prospective data. For both forms, apparent parameters were
increased by less than 10% compared to syrup and the effect
was not significant. Even if the study was not designed for the
comparison of galenic forms and does not allow to have a
significant coefficient, the value of the effect is very low and
makes it possible to conclude that there will be no clinical
impact. These results are consistent with those of Bouazza
et al.
3
and Piana et al.
4
who reported there were no differences
in the pharmacokinetics of lamivudine after administration of
the solid or liquid dosage form.
18,20
In contrast, Vanprapar
et al.
19
and Kassirye et al.
5
have observed higher 3TC exposure
in children with the dispersible tablets versus oral liquid. These
studies, including our current study, are population PK studies,
in which it is more difficult to identify a difference in ab-
sorption. Increased absorption could be an explanation for the
higher exposure of the dispersible tablet formulation versus oral
liquid in two other studies with full PK curves (as Cmax was
increased with 55 and 59%). Finally, an explanation for this
differencefoundinthesetwostudiescouldbethewayof
splitting the tablets which is not necessarily very reproducible.
In conclusion, the three dosage forms (syrup, tablet,
orodispersible tablet) had no influence on the pharmaco-
kinetics of lamivudine. Our results provide reassuring
added value for the use of cART drug regimen among
young children living with HIV in the context of scarce
therapeutic options.
Declaration of Conflicting Interests
The authors declared no potential conflicts of interest with respect
to the research, authorship, and/or publication of this article.
Funding
The authors received no financial support for the research, au-
thorship, and/or publication of this article.
ORCID iD
Claire Pressiat https://orcid.org/0000-0003-0728-2701
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Appendix 1
The ANRS 12206 MONOD Collaboration
Study Group (as of July 7th, 2015).
Participating sites:
Burkina Faso, Ouagadougou: Centre de Recherche In-
ternational pour la Sant´
e: Malik Coulibaly, D´
esir´
e Lucien
Dahourou, Nicolas Meda (co-investigator) Colette Ou´
e-
draogo, Mamadou Sawadogo, Wilfried Som´
e, D´
esir´
e
Sondo, Elisabeth Thio. CHU Charles De Gaulle : Ma-
madou Barry, William Hiembo, Fla Kou´
eta, Adama
Ouattara, Moussa Ou´
edraogo, Rasmata Ou´
edraogo, Sylvie
Ou´
edraogo, Bernadette Congo, Rose Barry, Diarra Y´
e,
CHU Yalgado Ou ´
edraogo: Malika Congo, Edouard Min-
´
en´
e, Marie Coulibaly, Pierre Innocent Guissou Angèle
Kalmogho, Ludovic Kam, Emile Ou´
edraogo, Lassana
Sangar´
e, Caroline Yonaba. Programme Sectoriel Sant´
ede
Lutte contre le SIDA et les IST : Sylvestre Tiendrebeogo.
Programme d’Appui au Monde Associatif et Commu-
nautaire (PAMAC) : Odette Ky-Zerbo.
Cˆ
ote d’Ivoire, Abidjan: Programme PACCI: Xavier
Anglaret, Clarisse Amani-Boss´
e, Divine Avit, Christine
Danel, Serge Eholi´
e, Didier Ekou´
evi, Eulalie Kanga, Su-
zanne Kouadio, S´
everin Lennaud, Maxime Aim´
e Oga,
Th´
erèse N’Dri-Yoman. CHU Cocody : Madeleine
Pressiat et al. 139
Amorissani-Folquet, Evelyne Dainguy, Beugre Kouassi,
Jean-Claude Kouassi, Gladys Oka. CHU Yopougon : Kader
Keita, Jean Yves Lambin, François Eboua Tanoh, Mar-
guerite Timit´
e-Konan (co-investigator). Site Abobo-Avo-
catier : V´
eronique Mea-Assande, Site CePReF-enfants :
Addi Edmond Aka, Hortense Aka-Dago, Sylvie N’Gbeche,
Eugène Messou. Laboratory CeDReS : Arlette Emieme,
Fatoumata Kon ´
e, Herv´
e Menan, Thomas Toni, Vincent
Yapo. Programme National de Prise en Charge : Kouam´
e
Abo, Irma Ahoba, David Aka. FSU Abobo-Avocatier :
Gbam´
en´
e Kouassi. Pharmacie de la Sant´
e Publique : Carine
Kodo ; Implementers : Tour´
e Siaka, Pety Tour´
e (ACONDA),
Fassinou Ekouevi (EGPAF), Ida Viho (ICAP), Anthony
Richard Tanoh, Olivier Bl´
e (Fondation ARIEL GLASER).
Community representants: Yaya Coulibaly (RIP+), Phil-
omène Takouo (ONG Bayema).Programme ESTHER : Jean
Marie Massumbuko. CIRBA : Kouadio Kouakou, Pro-
gramme National de Sant´
e Infantile: Doroth´
ee Koumi,
Programme Elargi de Vaccination : Bert´
eKon
´
e.
Methodology and Data Management Center: Inserm
U897, Institut de Sant´
e Publique, d’´
Epid´
emiologie et de
D´
eveloppement, University of Bordeaux, France: Sophie
Dattez, Sophie Desmonde, Julie Jesson, Sophie Karcher,
J´
erˆ
ome Le Carrou, Val ´
eriane Leroy (Coordinating inves-
tigator), Karen Malateste, Camille Ndondoki, Pierre
Touret. Methodological Support: Caroline Bouyssou,
Geneviève Chˆ
ene, Val´
erie Conte, Delphine Gabillard,
Va l ´
erie Journot, Roger Salamon.
MEREVA, Bordeaux. Website: http://mereva.isped.u-
bordeaux2.fr/monod/Accueil.aspx
Supporting teams: Luxembourg Institute of Health,
Luxemburg: Vic Arendt (co-investigator), Carole Devaux,
Jean-Claude Schmit.
Hˆ
opital Universitaire Des Enfants Reine Fabiola,
Bruxelles, Belgique: Philippe Lepage (co-investigator).
Hˆ
opital Necker-Enfants Malades Assistance Publique-
Hopitaux de Paris and EA8, Paris-Descartes: St ´
ephane
Blanche (co-investigator), Deborah Hirt, Christine Rou-
zioux, Claire Pressiat, Jean-Marc Treluyer, Saik Urien.
Commissariat `
al’Energie Atomique: Alain Pruvost (CEA),
Laboratoire de virologie, Hopital Saint-Louis : Marie-
Laure Chaix-Baudier.
UMR 1058 "Pathogenesis and Control of Chronic In-
fections" INSERM - Universit´
e Montpellier –EFS,
Montpellier, France: Philippe Van de Perre (co-
investigator).
Administrative Team: Elodie Vernoux (Bordeaux,
France), Aminata Par´
e-Karambiri (Ouagadougou, Burkina
Faso), Zouma Tinto (Ouagadougou, Burkina Faso),
Adoulaye Cisse (Abidjan, C ˆ
ote d’Ivoire), Madikona Dosso
(Abidjan, Cˆ
ote d’Ivoire).
MONOD ANRS 12206 Scientific Steering Commit-
tee: Roger Salamon (Chair, Bordeaux, France), Val ´
eriane
Leroy (Coordinating investigator, Bordeaux, France),
Nicolas Meda (Co-Investigator, Ouagadougou, Burkina
Faso), Marguerite Timite-Konan (Co-Investigator, Abid-
jan, Cˆ
ote d’Ivoire), Vic Arendt (Co-Investigateur, Lux-
embourg), St´
ephane Blanche (Co-Investigator, Paris,
France), Philippe Lepage (Co-Investigator, Bruxelles,
Belgique), Philippe Van de Perre (Co-Investigator,
Montpellier, France), François Dabis (Bordeaux,
France), Jean-Claude Schmit (CRP-Sant´
e, Luxembourg).
MONOD ANRS 12206 trial independent data
monitoring committee meeting: Dominique Costagliola
(Chair, Paris, France), Mark Cotton (Cape Town, South
Africa), Carlo Giaquito (Bologna, Italie), Diana Gibb
(London, UK), Elisabeth Menu (Paris, France).
Promotor: Inserm-ANRS, France: Jean-François Del-
fraissy (Director), Brigitte Bazin, Marie de Solère, Claire
Rekacewicz.
ClinicalTrial.gov registry n°NCT01127204: The
content is solely the responsibility of the authors and does
not necessarily represent the official views of the French
INSERM-ANRS, EDCTP, or University of Bordeaux.
140 Antiviral Therapy 26(6-8)