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Papers by Clotilde Allavena

British Journal of Clinical Pharmacology, Aug 4, 2020

AimsPolypharmacy increase the risk of drug–drug interactions (DDIs) in the elderly population liv... more AimsPolypharmacy increase the risk of drug–drug interactions (DDIs) in the elderly population living with human immunodeficiency virus (HIV). Several expert databases can be used to evaluate DDIs. The aim of the study was to describe actual DDIs between antiretroviral drugs and comedications in an elderly population and to compare grading of the DDIs in 3 databases.MethodsAll treatments of HIV‐infected subjects aged 65 years and older were collected in 6 French HIV centres. Summary of Product Characteristic (SPC), French DDI Thesaurus (THES), and Liverpool HIV DDI website (LIV) were used to define each DDI and specific grade. DDIs were classified in yellow flag interaction (undefined grade in SPC and THES or potential weak interaction in LIV), amber flag interaction (to be considered/precaution of use in SPC and THES and potential interaction in LIV) and red flag interaction (not recommended/contraindication in SPC and THES and do not administer/contraindication in LIV).ResultsAmong 239 subjects included, 60 (25.1%) had at least 1 DDI for a total of 126 DDIs: 23/126 red flag DDIs were identified in 17 patients. All these 23 DDIs were identified in LIV. THES and SPC missed 6 and 1 red flag DDIs, respectively. Seven of 23 red flag DDIs were identified in the 3 databases concomitantly.ConclusionPolypharmacy is frequent in this elderly HIV population leading to DDI in a quarter of the subjects. The discrepancies between databases can be explained by differences in analysis methods. A consensus between databases would be helpful for clinicians.

Medecine Et Maladies Infectieuses, Jun 1, 2014

Introduction – objectifs Les troubles du sommeil (TS) sont frequents chez les PVVIH mais aucune e... more Introduction – objectifs Les troubles du sommeil (TS) sont frequents chez les PVVIH mais aucune etude recente n’a evalue leur prevalence et les facteurs de risque (FR) a l’ere des traitements antiretroviraux (ARV) puissants et bien toleres. Materiels et methodes Le but de cette etude transversale est d’evaluer la prevalence et les FR associes aux TS. Un questionnaire sur la qualite de vie (WHO QOL HIV BREF), la qualite du sommeil (questionnaire de Pittsburgh, Index PSQI) et la depression (BDI II) etait propose aux PVVIH vus en consultation dans un des 6 centres du COREVIH Pays de la Loire. Resultats De novembre. 2012 a mai 2013, 1 354 patients ont ete inclus : hommes 73,5 %, âge median 47 ans, IMC median 23,5, stade C 20,6 %, co-infection 13 %, lipodystrophie 11,8 %, dyslipidemie 20 %, HTA 15,1 % et diabete 3 %. La duree mediane d’infection VIH etait de 12,4 ans, le taux de CD4 median de 604/mm 3 ; 94 % des PVVIH etaient sous ARV dont 86 % avec une charge virale indetectable ; 56,7 % avaient un travail, 38,7 % fumaient du tabac, 11,7 % du cannabis et 9 % etaient buveurs excessifs ; 83 % sont nes en France et 14,7 % en Afrique. La duree mediane de sommeil etait de 7 heures. 47 % des PVVIH presentaient des TS (score PSQI > 5), plus frequents chez les femmes (56,4 %) que chez les hommes (43,9 %) (p 19). En analyse multivariee, les facteurs statistiquement significatifs (p 10 ans. Conclusion Pres de la moitie des PVVIH ont des TS. Ces troubles sont lies aux conditions sociales et psychologiques. La prise en charge des depressions pourrait ameliorer la qualite du sommeil.

Innovation in Aging, Jun 30, 2017

Journal of Antimicrobial Chemotherapy

Objectives Even in an ‘optimal’ health system, patients’ characteristics may have an impact on th... more Objectives Even in an ‘optimal’ health system, patients’ characteristics may have an impact on their care. We investigated whether age, gender and place of birth have an impact in the HIV care continuum in France, a country with a universal free healthcare system. Methods We estimated differences in the 5 year restricted mean percentage of person-time spent (i) in care, (ii) receiving ART and (iii) on ART and virally suppressed among 2432 (30.2%) women, 3925 MSM (48.7%) and 1709 men who have sex with women (MSW; 21.2%) entering care in the Dat’AIDS French prospective cohort between 1 January 2013 and 31 December 2017. Trial registration: Clinicaltrials.gov reference NCT02898987. Results Men and women spent 85.6% and 82.8% of person-time on ART and 69.9% and 65% suppressed, respectively. MSM, MSW and women spent 86.9%, 82.6% and 82.8% of person-time on ART and 72.5%, 63.7% and 65% suppressed, respectively. Patients born in France (47%) and patients born abroad spent 87.9% and 81.9% o...

Scientific Data

The International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) COVID-19 da... more The International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) COVID-19 dataset is one of the largest international databases of prospectively collected clinical data on people hospitalized with COVID-19. This dataset was compiled during the COVID-19 pandemic by a network of hospitals that collect data using the ISARIC-World Health Organization Clinical Characterization Protocol and data tools. The database includes data from more than 705,000 patients, collected in more than 60 countries and 1,500 centres worldwide. Patient data are available from acute hospital admissions with COVID-19 and outpatient follow-ups. The data include signs and symptoms, pre-existing comorbidities, vital signs, chronic and acute treatments, complications, dates of hospitalization and discharge, mortality, viral strains, vaccination status, and other data. Here, we present the dataset characteristics, explain its architecture and how to gain access, and provide tools to facilitate ...

Background: Raltegravir (RAL) has favorable tolerability and safety profile, with few and managea... more Background: Raltegravir (RAL) has favorable tolerability and safety profile, with few and manageable drug interactions. The use of RAL 1200 mg once daily (qd) for first-line therapy is well established. We assessed efficacy and safety of RAL 1200 mg qd, as part of triple cART, for maintenance strategy.Methods: The QDISS trial (NCT03195452) was a 48-week multicenter, single-arm, open-label study designed to evaluate the ability of 2 NRTIs + RAL 1200 mg qd to maintain virological suppression in HIV-1 infected subjects on a stable cART with 2 NRTIs and a third agent for at least 6 months. The primary endpoint was the proportion of participants with HIV-1 RNA <50 copies/mL at week 24, by the FDA snapshot algorithm.Results: Of 100 participants 91% maintained viral suppression (95% CI: 83.6-95.8) at week 24 and 89% (81.2-94.4) at week 48. At week 24, there was one virological failure, without emergence of resistance-associated mutation and 10 participants had discontinued, 4 because of...

Background: In the general population, sport activity is associated with better health and better... more Background: In the general population, sport activity is associated with better health and better self-esteem. Among people living with HIV (PLHIV), sport activity could be associated with better self-esteem. The main objective of our study was to assess the association between sport activity and self-esteem among people living with HIV. The secondary objectives were to evaluate the association between sport and fatigue, sport and pain.Methods: We performed a cross-sectional observational study among PLHIV in our region. Each adult seen in routine HIV care was proposed to participate to the study. Participants had to fulfill self-questionnaires about sport activity, self-esteem, strength, and pain.Results: Among the 1160 people included in the study, 47% performed sport activity. The self-esteem score was better in the sporting group compared with the non sporting group (Rosenberg mean scale 32.7/40 versus 31.9 ; p=0.01). The FACIT-F total score showed a better strength in the sport...

Science, 2022

We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine i... more We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine individuals with this variant had a 0.54 to 0.74 log 10 increase (i.e., a ~3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6604 individuals with other subtype-B strains. Without treatment, advanced HIV—CD4 cell counts below 350 cells per cubic millimeter, with long-term clinical consequences—is expected to be reached, on average, 9 months after diagnosis for individuals in their thirties with this variant. Age, sex, suspected mode of transmission, and place of birth for the aforementioned 109 individuals were typical for HIV-positive people in the Netherlands, which suggests that the increased virulence is attributable to the viral strain. Genetic sequence analysis suggests that this variant arose in the 1990s from de novo mutation, not recombination, with increased transmissibility and an unfamiliar molecular mechanism of virul...

Infectious Diseases and Therapy, 2021

The two-drug regimen dolutegravir plus lamivudine demonstrated durable efficacy for up to 3 years... more The two-drug regimen dolutegravir plus lamivudine demonstrated durable efficacy for up to 3 years in phase III studies and a high barrier to resistance in treatment-naive and virologically suppressed people with HIV (PWH). This systematic literature review summarizes real-world evidence evaluating effectiveness and safety of dolutegravir plus lamivudine. We searched Ovid MEDLINE

Infection, 2021

Background The ISARIC prospective multinational observational study is the largest cohort of hosp... more Background The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs...

Journal of the European Academy of Dermatology and Venereology, 2020

BackgroundAlthough antiretroviral therapy (ART) has reduced the risk of Kaposi sarcoma (KS), KS c... more BackgroundAlthough antiretroviral therapy (ART) has reduced the risk of Kaposi sarcoma (KS), KS cases still occur in HIV‐infected people.ObjectiveTo describe all KS cases observed between 2010 and 2015 in a country with high ART coverage.MethodsRetrospective study using longitudinal data from 44 642 patients in the French Dat’AIDS multicenter cohort. Patients’ characteristics were described at KS diagnosis according to ART exposure and to HIV‐plasma viral load (HIV‐pVL) (≤50 or >50) copies/mL.ResultsAmong the 209 KS cases diagnosed during the study period, 33.2% occurred in ART naïve patients, 17.3% in ART‐experienced patients and 49.5% in patients on ART, of whom 23% for more than 6 months. Among these patients, 24 (11.5%) had HIV‐pVL ≤50 cp/mL, and 16 (66%) were treated with a boosted‐PI‐based regimen. The distribution of KS localization did not differ by ART status nor by year of diagnosis.LimitationsData on human herpesvirus 8, treatment modalities for KS and response rate we...

Clinical Infectious Diseases, 2019

Background We assessed prevalence of multimorbidity (MM) according to year of human immunodeficie... more Background We assessed prevalence of multimorbidity (MM) according to year of human immunodeficiency virus (HIV) diagnosis in elderly people living with HIV (PLWH). Methods This was a cross-sectional study of MM in PLWH aged ≥70 years from the Dat’AIDS French multicenter cohort. MM was defined as at least 3 coexistent morbidities of high blood pressure, diabetes mellitus, osteoporosis, non-AIDS cancer, chronic renal failure, cardiovascular and cerebrovascular disease, obesity, undernutrition, or hypercholesterolemia. Logistic regression models evaluated the association between MM and calendar periods of HIV diagnosis (1983–1996, 1997–2006, and 2007–2018). The secondary analysis evaluated MM as a continuous outcome, and a sensitivity analysis excluded PLWH with nadir CD4 count <200 cells/μL. Results Between January 2017 and September 2018, 2476 PLWH were included. Median age was 73 years, 75% were men, median CD4 count was 578 cells/μL, and 94% had controlled viremia. MM prevalenc...

PLOS ONE, 2019

¶ Membership of the Dat'AIDS study group is provided in the Acknowledgments.

Clinical Infectious Diseases, 2019

Background In late 2013, France was one of the first countries to recommend initiation of combina... more Background In late 2013, France was one of the first countries to recommend initiation of combination antiretroviral therapy (cART) irrespective of CD4 cell count. Methods To assess the impact of achieving the second and third Joint United Nations Programme on HIV/AIDS 90-90-90 targets (ie, 90% of diagnosed people on sustained cART, and, of those, 90% virologically controlled) on human immunodeficiency virus (HIV) incidence, we conducted a longitudinal study to describe the epidemiology of primary HIV infection (PHI) and/or recent HIV infection (patients with CD4 cell count ≥500/mm3 at HIV diagnosis; (PRHI) between 2007 and 2017 in a large French multicenter cohort. To identify changes in trends in PHI and PRHI, we used single breakpoint linear segmented regression analysis. Results During the study period, 61 822 patients were followed in the Dat’AIDS cohort; 2027 (10.0%) had PHI and 7314 (36.1%) had PRHI. The second and third targets were reached in 2014 and 2013, respectively. Th...

Value in Health, 2018

The total number of treatments avoided increased from 10,095 children after introduction of vacci... more The total number of treatments avoided increased from 10,095 children after introduction of vaccine to 30,286 children in fifth year. ConClusions: The introduction of Malaria vaccine for children younger than 5 years by Global fund in Rwanda may be affordable when compared to the amount money spent on treatment.

The Journal of antimicrobial chemotherapy, Jan 13, 2018

In the ANRS 165 DARULIGHT study (NCT02384967) carried out in HIV-infected patients, the use of a ... more In the ANRS 165 DARULIGHT study (NCT02384967) carried out in HIV-infected patients, the use of a darunavir/ritonavir-containing regimen with a switch to a reduced dose of darunavir maintained virological efficacy (≤50 copies/mL) for 48 weeks with a good safety profile. To assess the total and unbound blood plasma pharmacokinetics of darunavir and associated antiretrovirals, and their penetration into semen before and after dose reduction. Patients receiving a darunavir/ritonavir (800/100 mg q24h)-containing regimen for >6 months with plasma HIV-RNA ≤50 copies/mL for >12 months were switched to 400/100 mg darunavir/ritonavir q24h at week 0. A 24 h intensive pharmacokinetic blood sampling and a trough seminal sampling were performed before (week 0) and after (week 12) dose reduction. Individual pharmacokinetic parameter estimates were obtained using non-linear mixed-effect modelling for darunavir/ritonavir in blood plasma and used to test for bioequivalence, whereas darunavir/ri...

The Journal of antimicrobial chemotherapy, 2018

The OPTIPRIM-ANRS 147 trial compared intensive combination ART (darunavir/ritonavir, tenofovir di... more The OPTIPRIM-ANRS 147 trial compared intensive combination ART (darunavir/ritonavir, tenofovir disoproxil fumarate/emtricitabine, raltegravir and maraviroc) started early during primary HIV-1 infection with standard tritherapy with darunavir/ritonavir, tenofovir disoproxil fumarate and emtricitabine. From month 6 to 18, the percentage of viral load values <50 copies/mL was lower in the pentatherapy arm than in the tritherapy arm. Here we compared antiretroviral drug concentrations between the two arms. Plasma samples were collected from 50 patients at various times after drug administration. A Bayesian approach based on published population pharmacokinetic models was used to estimate residual drug concentrations (Ctrough) and exposures (AUC) in each patient. A mixed linear regression model was then used to compare the AUC and Ctrough values of each drug used in both groups. Published models adequately described our data and could be used to predict Ctrough and AUC. No significant...

Medicine, 2016

The aim of the study was to investigate the impact of first-line combined antiretroviral therapy ... more The aim of the study was to investigate the impact of first-line combined antiretroviral therapy (cART) regimen on the course of CD8 + T-cell counts in human immunodeficiency virus (HIV)-infected patients. A retrospective observational study conducted on the French DAT'AIDS Cohort of HIV-infected patients. We selected 605 patients initiating a first-line cART between 2002 and 2009, and which achieved a sustained undetectable HIV plasma viral load (pVL) for at least 12 months without cART modification. The evolution of CD8 + T-cell counts according to cART regimen was assessed. CD8 + T-cell counts were assessed in 572 patients treated with 2NRTIs+1PI/r (n= 297), 2NRTIs+1NNRTI (n= 207) and 3NRTIs (n= 68). In multivariate analysis, after 12 months of follow-up, the 3NRTIs regimen was associated with a significantly smaller decrease of CD8 + T-cell count compared with NNRTI-containing regimens (-10.2 cells/mL in 3NRTIs vs-105.1 cells/mL; P=0.02) but not compared with PI-containing regimens (10.2 vs-60.9 cells/mL; P=0.21). After 24 months, the 3NRTIs regimen was associated with a smaller decrease of CD8 + T-cell count and % compared with PI/r-and NNRTI-containing regimens (0.2 in 3NRTIs vs-9.9 with PI/rregimens, P=0.001, and vs-11.1 with NNRTI-regimens, p < 0.0001). A focus analysis on 11 patients treated with an INSTIcontaining cART regimen during the study period showed after 12 months of follow-up, a median decrease of CD8 + T-cell count of-155 [inter quartile range:-302;-22] cells/mL. Our data highlight the fact that cART regimens have differential effects on CD8 pool down regulation. Abbreviations: cART = combined antiretroviral therapy, HIV = human immunodeficiency virus, INSTI = integrase strand transfer inhibitor, NNRTI = non-nucleotide reverse transcriptase inhibitor, NRTI = nucleotide reverse transcriptase inhibitor, PI/r = Ritonavirboosted protease inhibitor, pVL = plasma viral load.

Médecine du Sommeil, 2016

Objectif Les troubles du sommeil (TS) sont frequemment rapportes chez les PVVIH, mais l’on manque... more Objectif Les troubles du sommeil (TS) sont frequemment rapportes chez les PVVIH, mais l’on manque d’etudes sur leur prevalence et les facteurs de risque, a l’ere des antiretroviraux (ARV) puissants et bien toleres. Methodes Etude transversale chez des PVVIH de 6 centres hospitaliers des « Pays-de-la-Loire ». Les donnees medico-sociales etaient recueillies en consultation et le patient completait 3 auto-questionnaires sur la qualite du sommeil (questionnaire de Pittsburgh, index PSQI), la depression (BDI II) et la qualite de vie (WHO QOL HIV BREF). Resultats Entre novembre 2012 et mai 2013, 1354 patients ont ete inclus : 73,5 % d’hommes, âge median 47 ans, 83 % nes en France, 14,7 % en Afrique, stade C 21 %, duree mediane d’infection VIH 12,4 ans, CD4 median 604/mm3, 94 % sous ARV, charge virale indetectable chez 87 %. Trente-neuf pour cent fument du tabac, 11,7 % du cannabis, 9 % sont buveurs excessifs, 56,7 % travaillent, 52 % vivent en couple. Le temps de sommeil moyen est de 7 heures. 47 % des PVVIH ont des TS (score PSQI > 5), plus frequents chez les femmes (56,4 %) que chez les hommes (43,9 %) (p 19). Les patients avec TS ont une qualite de vie significativement moins bonne (p 10 ans. Conclusion Les TS chez les PVVIH sont plus lies aux conditions sociales et psychologiques qu’a l’infection VIH. La depression est frequente, sa prise en charge pourrait ameliorer la qualite du sommeil.

The Journal of antimicrobial chemotherapy, Jan 21, 2015

Therapeutic control of HIV replication reduces the size of the viral reservoir, particularly amon... more Therapeutic control of HIV replication reduces the size of the viral reservoir, particularly among central memory CD4+ T cells, and this effect might be accentuated by early treatment. We examined the effect of ART initiated at the time of the primary HIV infection (early ART), lasting 2 and 6 years in 11 and 10 patients, respectively, on the HIV reservoir in peripheral resting CD4+ T cells, sorted into naive (TN), central memory (TCM), transitional memory (TTM) and effector memory (TEM) cells, by comparison with 11 post-treatment controllers (PTCs). Between baseline and 2 years, CD4+ T cell subset numbers increased markedly (P < 0.004) and HIV DNA levels decreased in all subsets (P < 0.009). TTM cells represented the majority of reservoir cells at both timepoints, T cell activation status normalized and viral diversity remained stable over time. The HIV reservoir was smaller after 6 years of early ART than after 2 years (P < 0.019), and did not differ between PTCs and pati...

British Journal of Clinical Pharmacology, Aug 4, 2020

AimsPolypharmacy increase the risk of drug–drug interactions (DDIs) in the elderly population liv... more AimsPolypharmacy increase the risk of drug–drug interactions (DDIs) in the elderly population living with human immunodeficiency virus (HIV). Several expert databases can be used to evaluate DDIs. The aim of the study was to describe actual DDIs between antiretroviral drugs and comedications in an elderly population and to compare grading of the DDIs in 3 databases.MethodsAll treatments of HIV‐infected subjects aged 65 years and older were collected in 6 French HIV centres. Summary of Product Characteristic (SPC), French DDI Thesaurus (THES), and Liverpool HIV DDI website (LIV) were used to define each DDI and specific grade. DDIs were classified in yellow flag interaction (undefined grade in SPC and THES or potential weak interaction in LIV), amber flag interaction (to be considered/precaution of use in SPC and THES and potential interaction in LIV) and red flag interaction (not recommended/contraindication in SPC and THES and do not administer/contraindication in LIV).ResultsAmong 239 subjects included, 60 (25.1%) had at least 1 DDI for a total of 126 DDIs: 23/126 red flag DDIs were identified in 17 patients. All these 23 DDIs were identified in LIV. THES and SPC missed 6 and 1 red flag DDIs, respectively. Seven of 23 red flag DDIs were identified in the 3 databases concomitantly.ConclusionPolypharmacy is frequent in this elderly HIV population leading to DDI in a quarter of the subjects. The discrepancies between databases can be explained by differences in analysis methods. A consensus between databases would be helpful for clinicians.

Medecine Et Maladies Infectieuses, Jun 1, 2014

Introduction – objectifs Les troubles du sommeil (TS) sont frequents chez les PVVIH mais aucune e... more Introduction – objectifs Les troubles du sommeil (TS) sont frequents chez les PVVIH mais aucune etude recente n’a evalue leur prevalence et les facteurs de risque (FR) a l’ere des traitements antiretroviraux (ARV) puissants et bien toleres. Materiels et methodes Le but de cette etude transversale est d’evaluer la prevalence et les FR associes aux TS. Un questionnaire sur la qualite de vie (WHO QOL HIV BREF), la qualite du sommeil (questionnaire de Pittsburgh, Index PSQI) et la depression (BDI II) etait propose aux PVVIH vus en consultation dans un des 6 centres du COREVIH Pays de la Loire. Resultats De novembre. 2012 a mai 2013, 1 354 patients ont ete inclus : hommes 73,5 %, âge median 47 ans, IMC median 23,5, stade C 20,6 %, co-infection 13 %, lipodystrophie 11,8 %, dyslipidemie 20 %, HTA 15,1 % et diabete 3 %. La duree mediane d’infection VIH etait de 12,4 ans, le taux de CD4 median de 604/mm 3 ; 94 % des PVVIH etaient sous ARV dont 86 % avec une charge virale indetectable ; 56,7 % avaient un travail, 38,7 % fumaient du tabac, 11,7 % du cannabis et 9 % etaient buveurs excessifs ; 83 % sont nes en France et 14,7 % en Afrique. La duree mediane de sommeil etait de 7 heures. 47 % des PVVIH presentaient des TS (score PSQI > 5), plus frequents chez les femmes (56,4 %) que chez les hommes (43,9 %) (p 19). En analyse multivariee, les facteurs statistiquement significatifs (p 10 ans. Conclusion Pres de la moitie des PVVIH ont des TS. Ces troubles sont lies aux conditions sociales et psychologiques. La prise en charge des depressions pourrait ameliorer la qualite du sommeil.

Innovation in Aging, Jun 30, 2017

Journal of Antimicrobial Chemotherapy

Objectives Even in an ‘optimal’ health system, patients’ characteristics may have an impact on th... more Objectives Even in an ‘optimal’ health system, patients’ characteristics may have an impact on their care. We investigated whether age, gender and place of birth have an impact in the HIV care continuum in France, a country with a universal free healthcare system. Methods We estimated differences in the 5 year restricted mean percentage of person-time spent (i) in care, (ii) receiving ART and (iii) on ART and virally suppressed among 2432 (30.2%) women, 3925 MSM (48.7%) and 1709 men who have sex with women (MSW; 21.2%) entering care in the Dat’AIDS French prospective cohort between 1 January 2013 and 31 December 2017. Trial registration: Clinicaltrials.gov reference NCT02898987. Results Men and women spent 85.6% and 82.8% of person-time on ART and 69.9% and 65% suppressed, respectively. MSM, MSW and women spent 86.9%, 82.6% and 82.8% of person-time on ART and 72.5%, 63.7% and 65% suppressed, respectively. Patients born in France (47%) and patients born abroad spent 87.9% and 81.9% o...

Scientific Data

The International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) COVID-19 da... more The International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) COVID-19 dataset is one of the largest international databases of prospectively collected clinical data on people hospitalized with COVID-19. This dataset was compiled during the COVID-19 pandemic by a network of hospitals that collect data using the ISARIC-World Health Organization Clinical Characterization Protocol and data tools. The database includes data from more than 705,000 patients, collected in more than 60 countries and 1,500 centres worldwide. Patient data are available from acute hospital admissions with COVID-19 and outpatient follow-ups. The data include signs and symptoms, pre-existing comorbidities, vital signs, chronic and acute treatments, complications, dates of hospitalization and discharge, mortality, viral strains, vaccination status, and other data. Here, we present the dataset characteristics, explain its architecture and how to gain access, and provide tools to facilitate ...

Background: Raltegravir (RAL) has favorable tolerability and safety profile, with few and managea... more Background: Raltegravir (RAL) has favorable tolerability and safety profile, with few and manageable drug interactions. The use of RAL 1200 mg once daily (qd) for first-line therapy is well established. We assessed efficacy and safety of RAL 1200 mg qd, as part of triple cART, for maintenance strategy.Methods: The QDISS trial (NCT03195452) was a 48-week multicenter, single-arm, open-label study designed to evaluate the ability of 2 NRTIs + RAL 1200 mg qd to maintain virological suppression in HIV-1 infected subjects on a stable cART with 2 NRTIs and a third agent for at least 6 months. The primary endpoint was the proportion of participants with HIV-1 RNA <50 copies/mL at week 24, by the FDA snapshot algorithm.Results: Of 100 participants 91% maintained viral suppression (95% CI: 83.6-95.8) at week 24 and 89% (81.2-94.4) at week 48. At week 24, there was one virological failure, without emergence of resistance-associated mutation and 10 participants had discontinued, 4 because of...

Background: In the general population, sport activity is associated with better health and better... more Background: In the general population, sport activity is associated with better health and better self-esteem. Among people living with HIV (PLHIV), sport activity could be associated with better self-esteem. The main objective of our study was to assess the association between sport activity and self-esteem among people living with HIV. The secondary objectives were to evaluate the association between sport and fatigue, sport and pain.Methods: We performed a cross-sectional observational study among PLHIV in our region. Each adult seen in routine HIV care was proposed to participate to the study. Participants had to fulfill self-questionnaires about sport activity, self-esteem, strength, and pain.Results: Among the 1160 people included in the study, 47% performed sport activity. The self-esteem score was better in the sporting group compared with the non sporting group (Rosenberg mean scale 32.7/40 versus 31.9 ; p=0.01). The FACIT-F total score showed a better strength in the sport...

Science, 2022

We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine i... more We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine individuals with this variant had a 0.54 to 0.74 log 10 increase (i.e., a ~3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6604 individuals with other subtype-B strains. Without treatment, advanced HIV—CD4 cell counts below 350 cells per cubic millimeter, with long-term clinical consequences—is expected to be reached, on average, 9 months after diagnosis for individuals in their thirties with this variant. Age, sex, suspected mode of transmission, and place of birth for the aforementioned 109 individuals were typical for HIV-positive people in the Netherlands, which suggests that the increased virulence is attributable to the viral strain. Genetic sequence analysis suggests that this variant arose in the 1990s from de novo mutation, not recombination, with increased transmissibility and an unfamiliar molecular mechanism of virul...

Infectious Diseases and Therapy, 2021

The two-drug regimen dolutegravir plus lamivudine demonstrated durable efficacy for up to 3 years... more The two-drug regimen dolutegravir plus lamivudine demonstrated durable efficacy for up to 3 years in phase III studies and a high barrier to resistance in treatment-naive and virologically suppressed people with HIV (PWH). This systematic literature review summarizes real-world evidence evaluating effectiveness and safety of dolutegravir plus lamivudine. We searched Ovid MEDLINE

Infection, 2021

Background The ISARIC prospective multinational observational study is the largest cohort of hosp... more Background The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs...

Journal of the European Academy of Dermatology and Venereology, 2020

BackgroundAlthough antiretroviral therapy (ART) has reduced the risk of Kaposi sarcoma (KS), KS c... more BackgroundAlthough antiretroviral therapy (ART) has reduced the risk of Kaposi sarcoma (KS), KS cases still occur in HIV‐infected people.ObjectiveTo describe all KS cases observed between 2010 and 2015 in a country with high ART coverage.MethodsRetrospective study using longitudinal data from 44 642 patients in the French Dat’AIDS multicenter cohort. Patients’ characteristics were described at KS diagnosis according to ART exposure and to HIV‐plasma viral load (HIV‐pVL) (≤50 or >50) copies/mL.ResultsAmong the 209 KS cases diagnosed during the study period, 33.2% occurred in ART naïve patients, 17.3% in ART‐experienced patients and 49.5% in patients on ART, of whom 23% for more than 6 months. Among these patients, 24 (11.5%) had HIV‐pVL ≤50 cp/mL, and 16 (66%) were treated with a boosted‐PI‐based regimen. The distribution of KS localization did not differ by ART status nor by year of diagnosis.LimitationsData on human herpesvirus 8, treatment modalities for KS and response rate we...

Clinical Infectious Diseases, 2019

Background We assessed prevalence of multimorbidity (MM) according to year of human immunodeficie... more Background We assessed prevalence of multimorbidity (MM) according to year of human immunodeficiency virus (HIV) diagnosis in elderly people living with HIV (PLWH). Methods This was a cross-sectional study of MM in PLWH aged ≥70 years from the Dat’AIDS French multicenter cohort. MM was defined as at least 3 coexistent morbidities of high blood pressure, diabetes mellitus, osteoporosis, non-AIDS cancer, chronic renal failure, cardiovascular and cerebrovascular disease, obesity, undernutrition, or hypercholesterolemia. Logistic regression models evaluated the association between MM and calendar periods of HIV diagnosis (1983–1996, 1997–2006, and 2007–2018). The secondary analysis evaluated MM as a continuous outcome, and a sensitivity analysis excluded PLWH with nadir CD4 count <200 cells/μL. Results Between January 2017 and September 2018, 2476 PLWH were included. Median age was 73 years, 75% were men, median CD4 count was 578 cells/μL, and 94% had controlled viremia. MM prevalenc...

PLOS ONE, 2019

¶ Membership of the Dat'AIDS study group is provided in the Acknowledgments.

Clinical Infectious Diseases, 2019

Background In late 2013, France was one of the first countries to recommend initiation of combina... more Background In late 2013, France was one of the first countries to recommend initiation of combination antiretroviral therapy (cART) irrespective of CD4 cell count. Methods To assess the impact of achieving the second and third Joint United Nations Programme on HIV/AIDS 90-90-90 targets (ie, 90% of diagnosed people on sustained cART, and, of those, 90% virologically controlled) on human immunodeficiency virus (HIV) incidence, we conducted a longitudinal study to describe the epidemiology of primary HIV infection (PHI) and/or recent HIV infection (patients with CD4 cell count ≥500/mm3 at HIV diagnosis; (PRHI) between 2007 and 2017 in a large French multicenter cohort. To identify changes in trends in PHI and PRHI, we used single breakpoint linear segmented regression analysis. Results During the study period, 61 822 patients were followed in the Dat’AIDS cohort; 2027 (10.0%) had PHI and 7314 (36.1%) had PRHI. The second and third targets were reached in 2014 and 2013, respectively. Th...

Value in Health, 2018

The total number of treatments avoided increased from 10,095 children after introduction of vacci... more The total number of treatments avoided increased from 10,095 children after introduction of vaccine to 30,286 children in fifth year. ConClusions: The introduction of Malaria vaccine for children younger than 5 years by Global fund in Rwanda may be affordable when compared to the amount money spent on treatment.

The Journal of antimicrobial chemotherapy, Jan 13, 2018

In the ANRS 165 DARULIGHT study (NCT02384967) carried out in HIV-infected patients, the use of a ... more In the ANRS 165 DARULIGHT study (NCT02384967) carried out in HIV-infected patients, the use of a darunavir/ritonavir-containing regimen with a switch to a reduced dose of darunavir maintained virological efficacy (≤50 copies/mL) for 48 weeks with a good safety profile. To assess the total and unbound blood plasma pharmacokinetics of darunavir and associated antiretrovirals, and their penetration into semen before and after dose reduction. Patients receiving a darunavir/ritonavir (800/100 mg q24h)-containing regimen for >6 months with plasma HIV-RNA ≤50 copies/mL for >12 months were switched to 400/100 mg darunavir/ritonavir q24h at week 0. A 24 h intensive pharmacokinetic blood sampling and a trough seminal sampling were performed before (week 0) and after (week 12) dose reduction. Individual pharmacokinetic parameter estimates were obtained using non-linear mixed-effect modelling for darunavir/ritonavir in blood plasma and used to test for bioequivalence, whereas darunavir/ri...

The Journal of antimicrobial chemotherapy, 2018

The OPTIPRIM-ANRS 147 trial compared intensive combination ART (darunavir/ritonavir, tenofovir di... more The OPTIPRIM-ANRS 147 trial compared intensive combination ART (darunavir/ritonavir, tenofovir disoproxil fumarate/emtricitabine, raltegravir and maraviroc) started early during primary HIV-1 infection with standard tritherapy with darunavir/ritonavir, tenofovir disoproxil fumarate and emtricitabine. From month 6 to 18, the percentage of viral load values <50 copies/mL was lower in the pentatherapy arm than in the tritherapy arm. Here we compared antiretroviral drug concentrations between the two arms. Plasma samples were collected from 50 patients at various times after drug administration. A Bayesian approach based on published population pharmacokinetic models was used to estimate residual drug concentrations (Ctrough) and exposures (AUC) in each patient. A mixed linear regression model was then used to compare the AUC and Ctrough values of each drug used in both groups. Published models adequately described our data and could be used to predict Ctrough and AUC. No significant...

Medicine, 2016

The aim of the study was to investigate the impact of first-line combined antiretroviral therapy ... more The aim of the study was to investigate the impact of first-line combined antiretroviral therapy (cART) regimen on the course of CD8 + T-cell counts in human immunodeficiency virus (HIV)-infected patients. A retrospective observational study conducted on the French DAT'AIDS Cohort of HIV-infected patients. We selected 605 patients initiating a first-line cART between 2002 and 2009, and which achieved a sustained undetectable HIV plasma viral load (pVL) for at least 12 months without cART modification. The evolution of CD8 + T-cell counts according to cART regimen was assessed. CD8 + T-cell counts were assessed in 572 patients treated with 2NRTIs+1PI/r (n= 297), 2NRTIs+1NNRTI (n= 207) and 3NRTIs (n= 68). In multivariate analysis, after 12 months of follow-up, the 3NRTIs regimen was associated with a significantly smaller decrease of CD8 + T-cell count compared with NNRTI-containing regimens (-10.2 cells/mL in 3NRTIs vs-105.1 cells/mL; P=0.02) but not compared with PI-containing regimens (10.2 vs-60.9 cells/mL; P=0.21). After 24 months, the 3NRTIs regimen was associated with a smaller decrease of CD8 + T-cell count and % compared with PI/r-and NNRTI-containing regimens (0.2 in 3NRTIs vs-9.9 with PI/rregimens, P=0.001, and vs-11.1 with NNRTI-regimens, p < 0.0001). A focus analysis on 11 patients treated with an INSTIcontaining cART regimen during the study period showed after 12 months of follow-up, a median decrease of CD8 + T-cell count of-155 [inter quartile range:-302;-22] cells/mL. Our data highlight the fact that cART regimens have differential effects on CD8 pool down regulation. Abbreviations: cART = combined antiretroviral therapy, HIV = human immunodeficiency virus, INSTI = integrase strand transfer inhibitor, NNRTI = non-nucleotide reverse transcriptase inhibitor, NRTI = nucleotide reverse transcriptase inhibitor, PI/r = Ritonavirboosted protease inhibitor, pVL = plasma viral load.

Médecine du Sommeil, 2016

Objectif Les troubles du sommeil (TS) sont frequemment rapportes chez les PVVIH, mais l’on manque... more Objectif Les troubles du sommeil (TS) sont frequemment rapportes chez les PVVIH, mais l’on manque d’etudes sur leur prevalence et les facteurs de risque, a l’ere des antiretroviraux (ARV) puissants et bien toleres. Methodes Etude transversale chez des PVVIH de 6 centres hospitaliers des « Pays-de-la-Loire ». Les donnees medico-sociales etaient recueillies en consultation et le patient completait 3 auto-questionnaires sur la qualite du sommeil (questionnaire de Pittsburgh, index PSQI), la depression (BDI II) et la qualite de vie (WHO QOL HIV BREF). Resultats Entre novembre 2012 et mai 2013, 1354 patients ont ete inclus : 73,5 % d’hommes, âge median 47 ans, 83 % nes en France, 14,7 % en Afrique, stade C 21 %, duree mediane d’infection VIH 12,4 ans, CD4 median 604/mm3, 94 % sous ARV, charge virale indetectable chez 87 %. Trente-neuf pour cent fument du tabac, 11,7 % du cannabis, 9 % sont buveurs excessifs, 56,7 % travaillent, 52 % vivent en couple. Le temps de sommeil moyen est de 7 heures. 47 % des PVVIH ont des TS (score PSQI > 5), plus frequents chez les femmes (56,4 %) que chez les hommes (43,9 %) (p 19). Les patients avec TS ont une qualite de vie significativement moins bonne (p 10 ans. Conclusion Les TS chez les PVVIH sont plus lies aux conditions sociales et psychologiques qu’a l’infection VIH. La depression est frequente, sa prise en charge pourrait ameliorer la qualite du sommeil.

The Journal of antimicrobial chemotherapy, Jan 21, 2015

Therapeutic control of HIV replication reduces the size of the viral reservoir, particularly amon... more Therapeutic control of HIV replication reduces the size of the viral reservoir, particularly among central memory CD4+ T cells, and this effect might be accentuated by early treatment. We examined the effect of ART initiated at the time of the primary HIV infection (early ART), lasting 2 and 6 years in 11 and 10 patients, respectively, on the HIV reservoir in peripheral resting CD4+ T cells, sorted into naive (TN), central memory (TCM), transitional memory (TTM) and effector memory (TEM) cells, by comparison with 11 post-treatment controllers (PTCs). Between baseline and 2 years, CD4+ T cell subset numbers increased markedly (P < 0.004) and HIV DNA levels decreased in all subsets (P < 0.009). TTM cells represented the majority of reservoir cells at both timepoints, T cell activation status normalized and viral diversity remained stable over time. The HIV reservoir was smaller after 6 years of early ART than after 2 years (P < 0.019), and did not differ between PTCs and pati...