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Background: Identifying determinants for histologically proven high-grade anal intraepithelial lesions (hHSIL) in HIV-positive MSM would allow better targeted screening. Methods: APACHES is a prospective study of anal HPV and related-lesions in 513 HIV-positive MSM aged ≥35 in six clinics across France. At baseline, participants underwent high resolution anoscopy (HRA) with biopsy of suspicious lesions, preceded by anal swabs for liquid-based cytology, p16/Ki67 immunostaining, and HPV DNA. hHSIL diagnosis was established by histopathological review panel consensus, and determinants assessed by logistic regression. Results: Baseline hHSIL prevalence was 10.4% and did not differ significantly by age, sexual behaviour or any HIV/immunodeficiency markers. hHSIL prevalence was significantly elevated in participants that smoked (ORadj=2.6, 95%CI 1.3–5.5) or who, in concurrent anal swabs, had ASCUS/LSIL (3.6, 95% CI 1.4–9.3) or ASC-H/HSIL (22.2, 95% CI 6.8–72.6) cytologic abnormalities, p16/Ki67 dual positivity (3.4, 95%CI 1.5–7.5), or non16-HR HPV (13.0, 95%CI 1.7–102), but most notably, HPV16 (46.3, 6.1–355) infection. Previous diagnosis of low- (2.3, 95%CI 1.0–5.4) or high- (3.8, 95%CI 1.5–9.9) grade anal lesion also conveyed higher hHSIL risk. After controlling for patient-specific determinants, there remained significant clinic-specific effects, especially in higher risk groups (HPV16-positive participants: 31.3% hHSIL in clinics A-D versus 5.1% in clinics E-F, p

Background: This study aimed to compare the humoral responses to mRNA COVID-19 vaccination in people living with HIV (PWH) and HIV-negative individuals., Methods: We included PWH with an undetectable viral load under ART and HIV-negative participants from the French nationwide ANRS COV-POPART cohort who had received two doses of vaccine as a primary vaccination. We compared humoral response between controls and PWH, stratified by CD4 cell count (<200/mm 3 and ≥200/mm 3 CD4 cell counts) at 1, 6, and 12 months after primary vaccination., Results: A total of 1776 participants were included in this analysis, 684 PWH (99% were on ART, median CD4 counts 673 cells/mm 3 ) and 1092 controls. At 1 month, after adjustment on age, sex, and BMI, PWH had lower seroneutralization titers than controls, and PWH with <200 CD4 cell/mm 3 had lower anti-Spike SARS-CoV-2 IgG antibodies. Same results were found at 6 months. However, in participants who received a booster dose between 6 and 12 months postprimary vaccination, we did not observe differences between PWH and controls at 12 months., Conclusion: PWH had high responses to primary mRNA COVID-19 vaccination. In those who received a booster dose after 6 months, the humoral response at 12 months increased to similar levels to controls, even in those with low CD4 counts at baseline., Competing Interests: Declarations of competing interest PL has received payment or honoraria for lectures, presentations, speakers bureau, manuscript writing, or educational events from AstraZeneca, GlaxoSmithKline, Janssen, Moderna, Merck Sharp & Dohme, Pfizer, Sanofi Pasteur, Seqirus. KL has received payment or honoraria for lectures, presentations or educational events from GlaxoSmithKline, Moderna, Merck Sharp & Dohme, Gilead. ZM has received payment or honoraria for lectures and presentations from Sanofi Pasteur, GlaxoSmithKline, Merck Sharp & Dohme, Pfizer. VP has received honoraria for lectures and presentations from Moderna. OL has received payment or honoraria for lectures, presentations, speakers bureau, or educational events from Sanofi Pasteur; Pfizer, Janssen, Moderna, Merck Sharp & Dohme, Seqirus and grants from Sanofi Pasteur; Pfizer, Janssen, GlaxoSmithKline, Moderna. The other authors declare having no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: Monitoring tools that could provide quick predictions of tuberculosis (TB) treatment outcomes are urgently needed. Here, we assessed whether the evolution of selected biomarkers of innate immunity may help monitoring TB treatment response within 2 weeks of treatment initiation., Methods: ANRS12394-LILAC-TB was a proof-of-concept prospective study: adults with a rifampicin-susceptible TB who are HIV-negative and HIV-infected documented by a positive Xpert MTB/RIF test were enrolled in Cambodia and Côte d'Ivoire. Plasma concentrations of interleukin-1 receptor antagonist (IL-1Ra), interferon-γ-induced protein-10 and clusters of differentiation (CD) (scavenging CD163) were measured by commercial enzyme-linked immunosorbent assay kits. A Wilcoxon test for paired data was used for longitudinal comparisons., Results: A total of 55 patients were enrolled (women: 31%, median age: 37 years; median CD4 count in the 10 of 13 participants with HIV: 53 cells/mm 3 ). Overall, 83% were considered in TB treatment success. Compared with baseline, the IL-1Ra plasma levels significantly decreased as soon as week (W) 1, independent of HIV status (-71% in HIV-positive vs -33% in HIV-negative; P <0.001). The IP-10 plasma levels significantly decreased at W1 and W2 compared with baseline (P <0.0001); however, that decrease was less marked in participants with HIV., Conclusions: Our findings suggest that measuring IL-1Ra plasma levels with a standard enzyme-linked immunosorbent assay technique at baseline and then 1 week after TB treatment onset could help clinicians to quickly assess TB treatment response., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

HIV infection has been controlled only since the introduction of triple therapy in 1996, combining, as antiretroviral agents, two nucleoside reverse transcriptase inhibitors (NRTIs) and one protease inhibitor (PI). However, among the NRTIs, the thymidine analogues stavudine and zidovudine led to lipoatrophy, either generalized or associated with visceral fat hypertrophy and buffalo hump. These molecules also increased insulin resistance and the prevalence of diabetes. They were replaced by other NRTIs or non-NRTIs (NNRTIs) that were considered to be free of adipose tissue (AT) toxicity. More recently, the NRTI tenofovir disoproxyfumarate (TDF) and the NNRTI efavirenz have been associated with inhibition of fat gain but not with clear lipoatrophy. Otherwise, the use of PIs led to a phenotype of trunk fat hypertrophy associated with cardiometabolic complications. To avoid their adverse effects, PIs have recently been replaced by a new class of antiretrovirals, the integrase inhibitors (INSTIs), which are well tolerated and effective in controlling HIV. However, this class has been associated with global weight gain, which may be important and concerning for some people living with HIV (PWH). Also, in the NRTI class, TDF has often been replaced by tenofovir alafenamide (TAF) due to bone and renal toxicities, and TAF has been associated with global fat gain. The cardiometabolic consequences of INTIs and TAF are primarily related to the associated weight gain. In the global obesogenic worldwide context, PWH are gaining weight as well in relation to poor health life conditions. Taking in charge obesity uses the same strategies as those used in the general population., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Setting: Health measures taken during the pandemic deeply modified the clinical research practices. At the same time, the demand for the results of the COVID-19 trials was urgent. Thus, the objective of this article is to share Inserm's experience in ensuring quality control in clinical trials in this challenging context., Objectives: DisCoVeRy is a phase III randomized study that aimed at evaluating the safety and efficacy of 4 therapeutic strategies in hospitalized COVID-19 adult patients. Between March, 22nd 2020 and January, 20th 2021, 1309 patients were included. In order to guarantee the best quality of data, the Sponsor had to adapt to the current sanitary measures and to their impact on clinical research activity, notably by adapting Monitoring Plan objectives, involving the research departments of the participating hospitals and a network of clinical research assistants (CRAs)., Results: Overall, 97 CRAs were involved and performed 909 monitoring visits. The monitoring of 100% of critical data for all patients included in the analysis was achieved, and despite of the pandemic context, a conform consent was recovered for more than 99% of patients. Results of the study were published in May and September 2021., Discussion/conclusion: The main monitoring objective was met thanks to the mobilization of considerable personnel resources, within a very tight time frame and external hurdles. There is a need for further reflection to adapt the lessons learned from this experience to the context of routine practice and to improve the response of French academic research during a future epidemic., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: CFL, VT, ADI, VPS, NM, ADE, AM, FM, DB and FA have nothing to disclose. CB has received consulting fees from MYLAN and Da Volterra and participated on a DSMB for 4Living Biotech. MH has received funding from The Belgian Centre for Knowledge (KCE), the Fonds-Erasme-COVID-19-Université Libre de Bruxelles and an EU-Horizon 2020 grant, payement or honoraria for lectures from Pfizer, Gilead and INSM, support for attending meetings and/or travel from Pfizer and Gilead, participated on a DSMB for Gilead and is President of the Belgian Society of Infectious Diseases and Clinical Microbiology and expert for Belgian Taskforce on COVID therapeutics. The institution employing AF, CD, HE, JS, SCC, MD and SLM received support from the French government, the European Commission, the Region Ile de France, Gilead Sciences, Inc., Sanofi, Merck group and AbbVie for the DisCoVeRy study., (Copyright © 2023. Published by Elsevier Inc.)

Objectives: Our aim was to compare the clinical and virological outcomes in Omicron BA.1- and BA.2-infected patients who received sotrovimab with those in patients who received nirmatrelvir for the prevention of severe COVID-19., Methods: In this multi-centric, prospective ANRS 0003S CoCoPrev cohort study, patients at a high risk of progression of mild-to-moderate BA.1 or BA.2 COVID-19 who received sotrovimab or nirmatrelvir were included. The proportion of patients with progression to severe COVID-19, time between the start of treatment to negative PCR conversion, SARS-CoV-2 viral decay, and characterization of resistance variants were determined. A multi-variable Cox proportional hazard model was used to determine the time to negative PCR conversion and a mixed-effect model for the dynamics of viral decay., Results: Amongst 255 included patients, 199 (80%) received ≥3 vaccine doses, 195 (76%) received sotrovimab, and 60 (24%) received nirmatrelvir. On day 28, new COVID-19-related hospitalization occurred in 4 of 193 (2%; 95% CI, 1-5%) sotrovimab-treated patients and 0 of 55 nirmatrelvir-treated patients (p 0.24). One out of the 55 nirmatrelvir-treated patients died (2%; 95% CI, 0-10%). The median time to negative PCR conversion was 11.5 days (95% CI, 10.5-13) in the sotrovimab-treated patients vs. 4 days (95% CI, 4-9) in the nirmatrelvir-treated patients (p < 0.001). Viral decay was faster in the patients who received nirmatrelvir (p < 0.001). In the multi-variable analysis, nirmatrelvir and nasopharyngeal PCR cycle threshold values were independently associated with faster conversion to negative PCR (hazard ratio, 2.35; 95% CI, 1.56-3.56; p < 0.0001 and hazard ratio, 1.05; 95% CI, 1.01-1.08; p 0.01, respectively)., Conclusions: Early administration of nirmatrelvir in high-risk patients compared with that of sotrovimab was associated with faster viral clearance. This may participate to decrease transmission and prevent viral resistance., (Copyright © 2022 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Competing Interests: Declaration of interests All authors are members of the French COVID-19 Scientific Council. J-FD is the President of the Council.

Objectives: We aimed to investigate the 1-month humoral response to two or three doses of a messenger RNA coronavirus disease 2019 (COVID-19) vaccine as a primary vaccination regimen in specific populations compared with that in healthy adults., Methods: Agence Nationale Recherche contre le Sida (ANRS)0001S-COV-POPART (NCT04824651) is a French nation-wide, multi-centre, prospective, observational cohort study assessing the immune response to COVID-19 vaccines routinely administered to 11 sub-groups of patients with chronic conditions and two control groups. Patients and controls who received at least two vaccine doses and whose results 1 month after the second dose were available were included. The humoral response was assessed 1 month after the first, second and third doses (if applicable) based on the percentage of responders (positive for anti-Spike severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] IgG antibodies), geometric means of anti-Spike SARS-CoV-2 IgG antibodies (enzyme-linked immunosorbent assay) and proportion of participants with anti-SARS-CoV-2-specific neutralizing antibodies (in vitro neutralization assay for the original SARS-CoV-2 strain). All analyses were centralized., Results: We included 4091 participants in this analysis: 2979 participants from specific sub-populations and 1112 controls. Only 522 (17.5%) participants from the specific populations received three doses as a primary vaccination regimen. Patients living with human immunodeficiency virus, cancer and diabetes had high percentages of responders after two doses, whereas patients with solid organ transplants, allogeneic hematopoietic stem cell transplants and hypogammaglobulinaemia had the lowest percentage of responders (35.9% [95% CI, 29.2-43.0], 57.4% [95% CI, 48.1-66.3] and 77.1% [95% CI, 65.6-86.3], respectively). In those who received the third dose, the percentage of responders reached 54.2% (95% CI, 42.9-65.2) (vs. 32.3% [95% CI, 16.7-51.4] after 2 doses) among those with solid organ transplants and 73.9% (95% CI, 58.9-85.7) (vs. 56.1% [95% CI, 46.2-65.7] after 2 doses) among those with hematopoietic stem cell transplants. Similar results were found with anti-SARS-CoV-2-specific neutralizing antibodies., Conclusions: A lower humoral response to COVID-19 vaccines was observed in the specific populations compared with that in the controls. The third dose of this vaccine in the primary regimen had a positive effect on the percentages of patients who developed anti-Spike IgG antibodies and specific neutralizing antibodies., (Copyright © 2022 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background & Aims: Identifying individuals at higher risk of developing hepatocellular carcinoma (HCC) is pivotal to improve the performance of surveillance strategies. Herein, we aimed to evaluate the ability of single nucleotide polymorphisms (SNPs) to refine HCC risk stratification., Methods: Six SNPs in PNPLA3, TM6SF2, HSD17B13, APOE, and MBOAT7 affecting lipid turnover and one variant involved in the Wnt-β-catenin pathway (WNT3A-WNT9A rs708113) were assessed in patients with alcohol-related and/or HCV-cured cirrhosis included in HCC surveillance programmes (prospective CirVir and CIRRAL cohorts). Their prognostic value for HCC occurrence was assessed using Fine-Gray models combined into a 7-SNP genetic risk score (GRS). The predictive ability of two clinical scores (a routine non-genetic model determined by multivariate analysis and the external aMAP score) with/without the GRS was evaluated by C-indices. The standardised net benefit was derived from decision curves., Results: Among 1,145 patients, 86 (7.5%) developed HCC after 43.7 months. PNPLA3 and WNT3A-WNT9A variants were independently associated with HCC occurrence. The GRS stratified the population into three groups with progressively increased 5-year HCC incidence (Group 1 [n = 627, 5.4%], Group 2 [n = 276, 10.7%], and Group 3 [n = 242, 15.3%]; p <0.001). The multivariate model identified age, male sex, diabetes, platelet count, gamma-glutamyltransferase levels, albuminemia and the GRS as independent risk factors. The clinical model performance for 5-year HCC prediction was similar to that of the aMAP score (C-Index 0.769). The addition of the GRS to both scores modestly improved their performance (C-Indices of 0.786 and 0.783, respectively). This finding was confirmed by decision curve analyses showing only fair clinical net benefit., Conclusions: Patients with cirrhosis can be stratified into HCC risk classes by variants affecting lipid turnover and the Wnt-β-catenin pathway. The incorporation of this genetic information modestly improves the performance of clinical scores., Impact and Implications: The identification of patients at higher risk of developing liver cancer is pivotal to improve the performance of surveillance. Risk assessment can be achieved by combining several clinical and biological parameters used in routine practice. The addition of patients' genetic characteristics can modestly improve this prediction and will ultimately pave the way for precision medicine in patients eligible for HCC surveillance, allowing physicians to trigger personalised screening strategies., (Copyright © 2022 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background and Aims: Patients chronically infected with hepatitis B virus (HBV) are at high risk of liver fibrosis, cirrhosis and liver cancer, despite recent therapeutic advances. It is therefore crucial to find non-pharmaceutical options for liver fibrosis prevention in this population. Using cross-sectional data from the ANRS CO22 Hepather cohort, we aimed to identify socio-demographic and modifiable risk factors for significant fibrosis in chronic HBV patients., Methods: Logistic regression or Firth's penalized maximum likelihood logistic regression (according to outcome prevalence) multivariable models were used to test for associations between explanatory variables and significant fibrosis, as assessed by three non-invasive markers: aspartate aminotransferase to platelet ratio index (APRI), FIB-4, and gamma glutamyltransferase to platelet ratio (GPR). Analyses were stratified by HBV treatment status., Results: The study population comprised 2065 untreated and 1727 treated chronic HBV patients. Elevated coffee consumption was consistently associated with a lower risk of elevated fibrosis biomarkers in all three treated-participant models, suggesting a dose-response relationship (adjusted odds ratios for ≥3 cups/day versus 0 cups/day: 0.16, 0.35 and 0.62, p ≤ 0.002, according to APRI, FIB-4 and GPR, respectively). Other modifiable risk factors included tobacco and alcohol use., Conclusion: Elevated coffee consumption was consistently associated with a lower risk of significant liver fibrosis, as assessed by three non-invasive markers in treated chronic HBV patients. This result can be immediately used in real-world situations, as increasing coffee consumption may be beneficial for patients at risk of advanced liver disease., Competing Interests: Conflict of interest Stanislas Pol has served as a speaker, a consultant and an advisory board member for Janssen, Gilead, Roche, MSD, Abbvie, Biotest, Shinogi, Vivv, and LFB. He has received research funding from Gilead, Abbvie, Roche and MSD not connected to the present work. Fabrice Carrat reports grants from INSERM-ANRS during the implementation of this study and personal fees from Imaxio, outside the submitted work. The other authors have no conflict of interest to declare., (Copyright © 2022 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Objectives: We evaluated the clinical, virological and safety outcomes of lopinavir/ritonavir, lopinavir/ritonavir-interferon (IFN)-β-1a, hydroxychloroquine or remdesivir in comparison to standard of care (control) in coronavirus 2019 disease (COVID-19) inpatients requiring oxygen and/or ventilatory support., Methods: We conducted a phase III multicentre, open-label, randomized 1:1:1:1:1, adaptive, controlled trial (DisCoVeRy), an add-on to the Solidarity trial (NCT04315948, EudraCT2020-000936-23). The primary outcome was the clinical status at day 15, measured by the WHO seven-point ordinal scale. Secondary outcomes included quantification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in respiratory specimens and pharmacokinetic and safety analyses. We report the results for the lopinavir/ritonavir-containing arms and for the hydroxychloroquine arm, trials of which were stopped prematurely., Results: The intention-to-treat population included 583 participants-lopinavir/ritonavir (n = 145), lopinavir/ritonavir-IFN-β-1a (n = 145), hydroxychloroquine (n = 145), control (n = 148)-among whom 418 (71.7%) were male, the median age was 63 years (IQR 54-71), and 211 (36.2%) had a severe disease. The day-15 clinical status was not improved with the investigational treatments: lopinavir/ritonavir versus control, adjusted odds ratio (aOR) 0.83, (95% confidence interval (CI) 0.55-1.26, p 0.39), lopinavir/ritonavir-IFN-β-1a versus control, aOR 0.69 (95%CI 0.45-1.04, p 0.08), and hydroxychloroquine versus control, aOR 0.93 (95%CI 0.62-1.41, p 0.75). No significant effect of investigational treatment was observed on SARS-CoV-2 clearance. Trough plasma concentrations of lopinavir and ritonavir were higher than those expected, while those of hydroxychloroquine were those expected with the dosing regimen. The occurrence of serious adverse events was significantly higher in participants allocated to the lopinavir/ritonavir-containing arms., Conclusion: In adults hospitalized for COVID-19, lopinavir/ritonavir, lopinavir/ritonavir-IFN-β-1a and hydroxychloroquine improved neither the clinical status at day 15 nor SARS-CoV-2 clearance in respiratory tract specimens., (Copyright © 2021 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

The rate of mother-to-child transmission (MTCT) of HIV from breastfeeding is increasing relative to other causes of MTCT. Early effective preconception and antenatal antiretroviral therapy (ART) reduces intrauterine and intrapartum MTCT, whereas maternal post-partum HIV acquisition, untreated maternal HIV, and suboptimal postnatal maternal ART adherence increase the risk of MTCT through breastfeeding. Although the absolute number of cases of MTCT acquired through breastfeeding is decreasing, the rate of decrease is less than the decrease in intrauterine and intrapartum MTCT. Unless current strategies are universally applied, they might not be sufficient to eliminate MTCT due to breastfeeding. Urgent action is needed to evaluate and implement additional preventive biomedical strategies in high HIV prevalence and incidence settings to eliminate MTCT from breastfeeding. Preventive strategies include: pre-exposure prophylaxis in breastfeeding women who have an increased risk of acquiring HIV; postnatal reinforcement strategies, such as maternal retesting for HIV, maternal care reinforcement, and prophylaxis in infants exposed to HIV via breastmilk; and active (vaccine) or passive immunoprophylaxis with long-acting broadly neutralising antibodies., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background & Aims: Refining hepatocellular carcinoma (HCC) surveillance programs requires improved individual risk prediction. Thus, we aimed to develop algorithms based on machine learning approaches to predict the risk of HCC more accurately in patients with HCV-related cirrhosis, according to their virological status., Methods: Patients with compensated biopsy-proven HCV-related cirrhosis from the French ANRS CO12 CirVir cohort were included in a semi-annual HCC surveillance program. Three prognostic models for HCC occurrence were built, using (i) Fine-Gray regression as a benchmark, (ii) single decision tree (DT), and (iii) random survival forest for competing risks survival (RSF). Model performance was evaluated from C-indexes validated externally in the ANRS CO22 Hepather cohort (n = 668 enrolled between 08/2012-01/2014)., Results: Out of 836 patients analyzed, 156 (19%) developed HCC and 434 (52%) achieved sustained virological response (SVR) (median follow-up 63 months). Fine-Gray regression models identified 6 independent predictors of HCC occurrence in patients before SVR (past excessive alcohol intake, genotype 1, elevated AFP and GGT, low platelet count and albuminemia) and 3 in patients after SVR (elevated AST, low platelet count and shorter prothrombin time). DT analysis confirmed these associations but revealed more complex interactions, yielding 8 patient groups with varying cancer risks and predictors depending on SVR achievement. On RSF analysis, the most important predictors of HCC varied by SVR status (non-SVR: platelet count, GGT, AFP and albuminemia; SVR: prothrombin time, ALT, age and platelet count). Externally validated C-indexes before/after SVR were 0.64/0.64 [Fine-Gray], 0.60/62 [DT] and 0.71/0.70 [RSF]., Conclusions: Risk factors for hepatocarcinogenesis differ according to SVR status. Machine learning algorithms can refine HCC risk assessment by revealing complex interactions between cancer predictors. Such approaches could be used to develop more cost-effective tailored surveillance programs., Lay Summary: Patients with HCV-related cirrhosis must be included in liver cancer surveillance programs, which rely on ultrasound examination every 6 months. Hepatocellular carcinoma (HCC) screening is hampered by sensitivity issues, leading to late cancer diagnoses in a substantial number of patients. Refining surveillance periodicity and modality using more sophisticated imaging techniques such as MRI may only be cost-effective in patients with the highest HCC incidence. Herein, we demonstrate how machine learning algorithms (i.e. data-driven mathematical models to make predictions or decisions), can refine individualized risk prediction., Competing Interests: Conflict of interest Dr. Nahon has received honoraria from and/or consults for Abbvie, AstraZeneca, Bayer, Bristol-Myers Squibb, Eisai, Gilead, Ipsen, MSD, Roche. He received research grants from Abbvie and Bristol-Myers Squibb. Dr. Pol consults for and has received grants from Bristol-Myers Squibb, Gilead, Roche, and MSD. He consults for Gilead, Bristol-Myers Squibb, Boehringer Ingelheim, Janssen, Abbvie, Roche and MSD. Dr. Guyader has received honoraria and/or grants from Abbvie, Gilead, Janssen and MSD. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

The West and Central African region (WCAR) still registers some of the highest rates of new HIV infections worldwide (16%) despite a low prevalence of HIV (1.9%). In this region, only 48% of people living with HIV are aware of their HIV status. To fill this gap, HIV Self testing (HIVST) could potentially be an additional approach to overcome the barriers to diagnose HIV infected patients, therefore being one of the keys to unlock the first 90 as recommended by the World Health Organization (WHO) since 2016. However, many challenges remain for the adoption of HIVST in routine clinical practice in low prevalence settings and need to be contextualized to WCAR settings. We report in this paper some of the challenges and discuss opportunities for a successful implementation of HIVST in the WCAR., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Scaling-up the access to hepatitis C virus (HCV) diagnostics for people who use injecting drugs (PWID) is essential to reduce the HCV incidence in low and middle-income countries., Methods: A decision tree model was developed to compare the cost-effectiveness of 12 strategies for diagnosing HCV in Senegal with a health sector perspective. Strategies included HCV-Ab screening and confirmation of viraemia (based on HCV-RNA or HCV core antigen detection) or only the latter step. Laboratory assays and decentralized tools (point-of-care (POC) tests and dried blood spot (DBS) samples) were included. The base-case assumed a 38.9% seroprevalence, as reported in the PWID population of Dakar., Results: Compared to the cheapest strategy (POC HCV-Ab followed by POC HCV-RNA (S 5 )), one strategy remained un-dominated in the base-case: POC HCV-Ab followed by venepuncture-based laboratory HCV-RNA (S 3 ). Above a lost to follow-up testing rate of 2.3%, combining POC HCV-Ab with HCV-RNA on DBS (S 4 ) became more cost-effective than S 3 . Above this threshold, a single-step POC HCV-RNA (S 12 ) was also found un-dominated (ICER to S 5 =€3,297.50). S 5 , S 12 and S 4 cost €14.21, €17.03 and €36.55/screened individual. Incremental cost-effectiveness ratios (€/additional true positive case) were 2,164.82 (S 12 versus S 5 ) and 3,297.50 (S 4 versus S 12 ). Whenever HCV seroprevalence reached 55.5%, S 12 became more cost-effective than S 5 . Moreover, S 4 required a budget 2 to 2.5 times higher than S 5 or S 12 for diagnosing 90% of HCV-infected PWID in Dakar., Conclusion: A two-step POC-based strategy (S 5 ) would be the most cost-effective option among those proposed in this study for diagnosing HCV in PWID in Senegal. This study illustrates how the lack of secure financing and of data on PWID in LMICs, render difficult to identify the most sustainable strategy in those countries, as well as its implementation., (Copyright © 2019. Published by Elsevier B.V.)

Objectives: Sub-Saharan Africa is a region with high incidence of both human immunodeficiency virus (HIV) and cervical cancer. We conducted the first national study in Togo to assess prevalence of human papillomavirus (HPV), HIV and other sexually transmitted infections (STIs) among female sex workers (FSW)., Methods: A multicentric cross-sectional study was conducted among FSW recruited in hot spots (clubs, streets) in four Togolese cities. HPV and STIs were tested from cervical and anal swabs. HIV and syphilis were screened with rapid tests., Results: In all, 310 FSW were recruited; HIV and cervical high-risk HPV (hrHPV) prevalence were 10.6% (33/310) and 32.9% (102/310), respectively. The most frequent hrHPV types were HPV58 (13.6%, 19/140), HPV35 (12.9%, 18/140), HPV31 (12.1%, 17/140) and HPV16 (10.7%, 15/140). Prevalence of hrHPV and multiple hrHPV infections showed higher rates in HIV-positive than in HIV-negative FSW (48.5% versus 31.0%, p 0.04 and 21.2% versus 9.0%, p 0.03; respectively). Prevalence of hrHPV was higher in cervical than anal swabs (34.1% versus 20.7%, p 0.0004). High-risk HPV anal infections were more frequent among HIV-positive than HIV-negative FSW (51.9% versus 17.3%, p 2 × 10 -5 ). Concomitant anal and cervical hrHPV infections were present in 43.2% (41/95) of hrHPV-positive FSW. Overall prevalence in the cervix of Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium and Trichomonas vaginalis were 4.2%, 6.1%, 5.5% and 6.5%, respectively., Conclusions: This first African study on paired cervical and anal samples showed a high prevalence of genital HPV infections with a rather high rate of concomitant HPV infections but low type concordance. We report an unusual distribution of hrHPV types. These findings highlight the critical need for implementation of a national HPV vaccination strategy., (Copyright © 2019 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Although direct-acting antivirals have been used extensively to treat patients with chronic hepatitis C virus (HCV) infection, their clinical effectiveness has not been well reported. We compared the incidence of death, hepatocellular carcinoma, and decompensated cirrhosis between patients treated with direct-acting antivirals and those untreated, in the French ANRS CO22 Hepather cohort., Methods: We did a prospective study in adult patients with chronic HCV infection enrolled from 32 expert hepatology centres in France. We excluded patients with chronic hepatitis B, those with a history of decompensated cirrhosis, hepatocellular carcinoma, or liver transplantation, and patients who were treated with interferon-ribavirin with or without first-generation protease inhibitors. Co-primary study outcomes were incidence of all-cause mortality, hepatocellular carcinoma, and decompensated cirrhosis. The association between direct-acting antivirals and these outcomes was quantified using time-dependent Cox proportional hazards models. This study is registered with ClinicalTrials.gov, number NCT01953458., Findings: Between Aug 6, 2012, and Dec 31, 2015, 10 166 patients were eligible for the study. 9895 (97%) patients had available follow-up information and were included in analyses. Median follow-up was 33·4 months (IQR 24·0-40·7). Treatment with direct-acting antivirals was initiated during follow-up in 7344 patients, and 2551 patients remained untreated at the final follow-up visit. During follow-up, 218 patients died (129 treated, 89 untreated), 258 reported hepatocellular carcinoma (187 treated, 71 untreated), and 106 had decompensated cirrhosis (74 treated, 32 untreated). Exposure to direct-acting antivirals was associated with increased risk for hepatocellular carcinoma (unadjusted hazard ratio [HR] 2·77, 95% CI 2·07-3·71) and decompensated cirrhosis (3·83, 2·29-6·42). After adjustment for variables (age, sex, body-mass index, geographical origin, infection route, fibrosis score, HCV treatment-naive, HCV genotype, alcohol consumption, diabetes, arterial hypertension, biological variables, and model for end-stage liver disease score in patients with cirrhosis), exposure to direct-acting antivirals was associated with a decrease in all-cause mortality (adjusted HR 0·48, 95% CI 0·33-0·70) and hepatocellular carcinoma (0·66, 0·46-0·93), and was not associated with decompensated cirrhosis (1·14, 0·57-2·27)., Interpretation: Treatment with direct-acting antivirals is associated with reduced risk for mortality and hepatocellular carcinoma and should be considered in all patients with chronic HCV infection., Funding: INSERM-ANRS (France Recherche Nord & Sud Sida-HIV Hépatites), ANR (Agence Nationale de la Recherche), DGS (Direction Générale de la Santé), MSD, Janssen, Gilead, AbbVie, Bristol-Myers Squibb, and Roche., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objectives: High adherence is needed to maintain antiretroviral therapy efficacy. Few attempts at therapeutic patient education (TPE) have been made in sub-Saharan Africa. We describe patients' achievements before intervention and identified needs, TPE programme implementation and evaluation, and patients' satisfaction., Methods: The TPE programme was proposed to patients in the ANRS-12286/MOBIDIP trial. Beforehand, a directory of competences to manage HIV infection was designed. Patients' HIV-related knowledge and skills assessment was realised, leading to an educational contract. Evaluation was performed using a standardised collection form and a satisfaction survey., Results: Of 154 patients, 146 underwent TPE. During a median of 1.8 years, 47% of patients had ≥3 consultations. Educational assessment revealed limited knowledge about HIV disease. Conversely, patients had frequently managed issues of adherence or disclosure. A median of 12 objectives were considered per patient, and 75% were attained. Objectives from the cognitive domain were less frequently attained. Patients appeared satisfied with the intervention: more emphasis was placed on psycho-affective aspects or experience-sharing than on the acquisition of knowledge., Conclusion: Active listening, know-how and a space for discussion appear more important for patients than knowledge on disease or treatments., Practice Implications: In HIV care, the directory of learning objectives should be revised to include more objectives concerning practical skills for disease management., (Copyright © 2018 Elsevier B.V. All rights reserved.)

More than 3 million children aged less than 15years are infected with HIV worldwide, mainly in Sub-Saharan Africa. The survival of HIV-infected children depends on their access to antiretroviral therapy whose success mainly depends on a good life-long compliance with antiretroviral therapy. Given its complexity and specificity, assessment and monitoring of pediatric compliance with antiretroviral therapy is a major challenge. There is no consensus on a gold standard for monitoring compliance with antiretroviral therapy. Compliance is also influenced by many factors related to the child, the caregiver, the healthcare staff, the healthcare system, and antiretroviral drugs. This review aimed to assess scientific knowledge on pediatric compliance with antiretroviral therapy in Sub-Saharan Africa, and to identify areas for future interventions to improve compliance. Good compliance is essential to achieve the "90% coverage of children on antiretroviral therapy" gold standard of the World Health Organization, and to eliminate HIV infection by 2030., (Copyright © 2017. Published by Elsevier SAS.)

Hepatitis C virus (HCV) infection is associated with reduced patient survival following combined liver-kidney transplantation (LKT). The aim of this study was to assess the efficacy and safety of second-generation direct-acting antivirals (DAAs) in this difficult-to-treat population. The ANRS CO23 "Compassionate use of Protease Inhibitors in Viral C Liver Transplantation" (CUPILT) study is a prospective cohort including transplant recipients with recurrent HCV infection treated with DAAs. The present work focused on recipients with recurrent infection following LKT. The study population included 23 patients. All patients received at least one NS5B inhibitor (sofosbuvir) in their antiviral regimen an average of 90 months after LKT. Ninety-six percent of recipients achieved a sustained virological response (SVR) at week 12 (SVR12). In terms of tolerance, 39% of recipients presented with at least one serious adverse event. None of the patients experienced acute rejection during therapy and there were no deaths during follow-up. The glomerular filtration rate (GFR) decreased significantly from baseline to the end of therapy. However, this study did not show that the decline in GFR persisted over time or that it was directly related to DAAs. The DAA-based regimen is well tolerated with excellent results in terms of efficacy. It will become the gold standard for the treatment of recurrent HCV following LKT., (© 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: We aimed to describe changes in hepatitis B screening practices over a 3-year period among HIV-infected patients in West Africa., Methods: A medical chart review was conducted in urban HIV treatment centers in Ivory Coast (3 sites), Benin, Burkina Faso, Senegal, and Togo (1 site each). Among patients who started antiretroviral treatment between 2010 and 2012, 100 per year were randomly selected from each clinic. Demographic, clinical, and laboratory data was collected using a standardized questionnaire. We assessed changes in the proportion of patients screened over time and identified predictors of screening in a multivariable logistic regression., Results: A total of 2097 patients were included (median age: 37 years, 65.4% of women). Overall, 313 (14.9%) patients had been screened for hepatitis B, with an increase from 10.6% in 2010 to 18.9% in 2012 (P<0.001) and substantial differences across countries. In multivariable analysis, being aged over 45 years (adjusted odds ratio: 1.34 [1.01-1.77]) and having an income-generating activity (adjusted odds ratio: 1.82 [1.09-3.03]) were associated with screening for hepatitis B infection. Overall, 62 HIV-infected patients (19.8%, 95% confidence interval: 15.5-24.7) were HBsAg-positive and 82.3% of them received a tenofovir-containing drug regimen., Conclusion: Hepatitis B screening among HIV-infected patients was low between 2010 and 2012. The increasing availability of HBsAg rapid tests and tenofovir in first-line antiretroviral regimen should improve the rates of hepatitis B screening., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Background & Aims: We report the first real-life results of the sofosbuvir+daclatasvir combination in hepatitis C virus (HCV) genotype 1 infected patients., Methods: The France REcherche Nord&Sud Sida-hiv Hépatites (ANRS) CO22 HEPATHER "Therapeutic options for hepatitis B and C: A French cohort" is a multicentre observational cohort which aims to include 15,000 HCV- and 10,000 HBV-infected patients. We selected all participants (n=768) with a HCV genotype 1 who initiated sofosbuvir (400mg/day) and daclatasvir (60mg/day) before October 1st 2014, with or without ribavirin (1-1.2g/day) for a duration of 12weeks or 24weeks. The main endpoint criterion was sustained virological response at 12weeks (SVR12), defined by the absence of detectable HCV-RNA 12weeks after the last treatment intake. Missing SVR12 measurements were imputed using SVR24 measurements (n=45), otherwise considered as virological failure (n=18)., Results: A SVR12 was obtained in 729/768 (95%) patients, ranging from 92% (12-week sofosbuvir+daclatasvir) to 99% (24-week sofosbuvir+daclatasvir+ribavirin). The SVR12 rates did not significantly differ between the 24-week (550/574 (96%)) and the 12-week (179/194 (92%); p=0.0688) durations or between regimens with (165/169 (98%)) or without ribavirin (564/599 (94%); p=0.0850). The SVR12 rate was greater than 97% in non-cirrhotic patients irrespective of the treatment duration or the addition of ribavirin. Among cirrhotic patients, the SVR12 rate was higher with 24 than 12-week regimen (423/444 (95%) vs. 105/119 (88%); p=0.0054)., Conclusion: The sofosbuvir+daclatasvir combination is associated with a high rate of SVR12 in patients infected by genotype 1, with an optimal duration of 12weeks in non-cirrhotic and 24weeks in cirrhotic patients. The number of patients receiving ribavirin was too low to adequately assess its impact., Lay Summary: The sofosbuvir+daclatasvir combination of antiviral drugs is associated with a high rate (95%) of viral eradication in patients infected by HCV genotype 1. The best duration of a ribavirin-free sofosbuvir+daclatasvir combination seems to be 12weeks in non-cirrhotic patients and 24weeks for those with cirrhosis. Clinical trial number: NCT01953458., (Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

The French contribution to global public health over the past two centuries has been marked by a fundamental tension between two approaches: State-provided universal free health care and what we propose to call State humanitarian verticalism. Both approaches have historical roots in French colonialism and have led to successes and failures that continue until the present day. In this paper, the second in The Lancet's Series on France, we look at how this tension has evolved. During the French colonial period (1890s to 1950s), the Indigenous Medical Assistance structure was supposed to bring metropolitan France's model of universal and free public health care to the colonies, and French State imperial humanitarianism crystallised in vertical programmes inspired by Louis Pasteur, while vying with early private humanitarian activism in health represented by Albert Schweitzer. From decolonisation to the end of the Cold War (1960-99), French assistance to newly independent states was affected by sans frontièrisme, Health for All, and the AIDS pandemic. Since 2000, France has had an active role in development of global health initiatives and favoured multilateral action for health assistance. Today, with adoption of the 2030 Sustainable Development Goals and the challenges of non-communicable diseases, economic inequality, and climate change, French international health assistance needs new direction. In the context of current debate over global health as a universal goal, understanding and acknowledging France's history could help strengthen advocacy in favour of universal health coverage and contribute to advancing global equity through income redistribution, from healthy populations to people who are sick and from wealthy individuals to those who are poor., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Strategies to prevent postnatal mother-to-child transmission of HIV-1 in Africa, including infant prophylaxis, have never been assessed past 6 months of breastfeeding, despite breastfeeding being recommended up to 12 months after birth. We aimed to compare the efficacy and safety of infant prophylaxis with the two drug regimens (lamivudine or lopinavir-ritonavir) to prevent postnatal HIV-1 transmission up to 50 weeks of breastfeeding., Methods: We did a randomised controlled trial in four sites in Burkina Faso, South Africa, Uganda, and Zambia in children born to HIV-1-infected mothers not eligible for antiretroviral therapy (CD4 count >350 cells per μL). An independent researcher electronically generated a randomisation schedule; we then used sequentially numbered envelopes to randomly assign (1:1) HIV-1-uninfected breastfed infants aged 7 days to either lopinavir-ritonavir or lamivudine (paediatric liquid formulations, twice a day) up to 1 week after complete cessation of breastfeeding or at the final visit at week 50. We stratified the randomisation by country and used permuted blocks of four and six. We used a study label on drug bottles to mask participants, study physicians, and assessors to the treatment allocation. The primary outcome was infant HIV-1 infection between age 7 days and 50 weeks, diagnosed every 3 months with HIV-1 DNA PCR, in the modified intention-to-treat population (all who attended at least one follow-up visit). This trial is registered with ClinicalTrials.gov, number NCT00640263., Findings: Between Nov 16, 2009, and May 7, 2012, we enrolled and randomised 1273 infants and analysed 1236; 615 assigned to lopinavir-ritonavir or 621 assigned to lamivudine. 17 HIV-1 infections were diagnosed in the study period (eight in the lopinavir-ritonavir group and nine in the lamivudine group), resulting in cumulative HIV-1 infection of 1.4% (95% CI 0.4-2.5) and 1.5% (0.7-2.5), respectively. Infection rates did not differ between the two drug regimens (hazard ratio [HR] of lopinavir-ritonavir versus lamivudine of 0.90, 95% CI 0.35-2.34; p=0.83). Clinical and biological severe adverse events did not differ between groups; 251 (51%) infants had a grade 3-4 event in the lopinavir-ritonavir group compared with 246 (50%) in the lamivudine group., Interpretation: Infant HIV-1 prophylaxis with lopinavir-ritonavir was not superior to lamivudine and both drugs led to very low rates of HIV-1 postnatal transmission for up to 50 weeks of breastfeeding. Infant pre-exposure prophylaxis should be extended until the end of HIV-1 exposure and mothers should be informed about the persistent risk of transmission throughout breastfeeding., Funding: INSERM/National Agency for Research on AIDS and Viral Hepatitis (including funds from the Total Foundation), European Developing Countries Clinical Trials Partnership, Research Council of Norway., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Standard first-line antiretroviral therapy for HIV-1 infection includes two nucleoside or nucleotide reverse transcriptase inhibitors (NtRTIs), but these drugs have limitations. We assessed the 96 week efficacy and safety of an NtRTI-sparing regimen., Methods: Between August, 2010, and September, 2011, we enrolled treatment-naive adults into this randomised, open-label, non-inferiority trial in treatment-naive adults in 15 European countries. The composite primary outcome was change to randomised treatment before week 32 because of insufficient virological response, no virological response by week 32, HIV-1 RNA concentration 50 copies per mL or higher at any time after week 32; death from any cause; any new or recurrent AIDS event; or any serious non-AIDS event. Patients were randomised in a 1:1 ratio to receive oral treatment with 400 mg raltegravir twice daily plus 800 mg darunavir and 100 mg ritonavir once daily (NtRTI-sparing regimen) or tenofovir-emtricitabine in a 245 mg and 200 mg fixed-dose combination once daily, plus 800 mg darunavir and 100 mg ritonavir once daily (standard regimen). This trial was registered with ClinicalTrials.gov, number NCT01066962., Findings: Of 805 patients enrolled, 401 received the NtRTI-sparing regimen and 404 the standard regimen, with median follow-up of 123 weeks (IQR 112-133). Treatment failure was seen in 77 (19%) in the NtRTI-sparing group and 61 (15%) in the standard group. Kaplan-Meier estimated proportions of treatment failure by week 96 were 17·8% and 13·8%, respectively (difference 4·0%, 95% CI -0·8 to 8·8). The frequency of serious or treatment-modifying adverse events were similar (10·2 vs 8·3 per 100 person-years and 3·9 vs 4·2 per 100 person-years, respectively)., Interpretation: Our NtRTI-sparing regimen was non-inferior to standard treatment and represents a treatment option for patients with CD4 cell counts higher than 200 cells per μL., Funding: European Union Sixth Framework Programme, Inserm-ANRS, Gilead Sciences, Janssen Pharmaceuticals, Merck Laboratories., (Copyright © 2014 Elsevier Ltd. All rights reserved.)