Exclusive Oral Antibiotic Treatment for Hospitalized Community-Acquired Pneumonia: A Post-Hoc Analysis of a Randomized Clinical Trial.

OBJECTIVES: In this study, we aimed to assess the efficacy of different ways of administration and types of beta-lactams for hospitalized community-acquired pneumonia (CAP). METHODS: In this post-hoc analysis of a RCT on patients hospitalized for CAP (PTC trial) comparing 3-day versus 8-day durations of beta-lactams, which concluded to non-inferiority, we included patients who received either amoxicillin-clavulanate (AMC) or third-generation cephalosporin (3GC) regimens, and exclusively either intravenous or oral treatment for the first 3 days (followed by either 5 days of oral placebo or AMC according to randomization). Choice of route and molecule was left to the physician in charge. The main outcome was failure at 15 days after first antibiotic intake, defined as temperature>37.9°C, and/or absence of resolution/improvement of respiratory symptoms, and/or additional antibiotic treatment for any cause. The primary outcome according to route of administration was evaluated through logistic regression. Inverse probability treatment weighting (IPTW) with a propensity score model was used to adjust for non-randomization of treatment route and potential confounders. The difference in failure rates was also evaluated among several sub-populations (AMC versus 3GC treatments, or intravenous versus oral AMC, patients with multi-lobar infection, patients aged ≥ 65 years old, and patients with CURB65 scores of 3-4). RESULTS: We included 200 patients from the original trial, with 93/200 (46.5%) patients only treated with intravenous treatment and 107/200 (53.5%) patients only treated with oral therapy. Failure rate at Day 15 was not significantly different among patients treated with initial intravenous versus oral treatment (25/93 (26.9%) versus 28/107 (26.2%), aOR 0.973 (95%CI 0.519-1.823), p=0.932). Failure rates at Day 15 were not significantly different among the subgroup populations. CONCLUSIONS: Among hospitalized patients with CAP, there was no significant difference in efficacy between initial intravenous and exclusive oral treatment. TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov, NCT01963442.

Social conformism and confidence in systems as additional psychological antecedents of vaccination: a survey to explain intention for COVID-19 vaccination among healthcare and welfare sector workers, France, December 2020 to February 2021.

BackgroundThe start of the COVID-19 vaccination campaign among French healthcare and welfare sector workers in January 2021 offered an opportunity to study psychological antecedents of vaccination in this group.AimWe explored whether knowledge and attitude items related to social conformism and confidence in systems contributed to explaining intention for COVID-19 vaccination.MethodsWe developed a knowledge and attitude questionnaire with 30 items related to five established and two hypothetical psychological antecedents of vaccination (KA-7C). The online questionnaire was distributed from 18 December 2020 to 1 February 2021 through chain-referral via professional networks, yielding a convenience sample. We used multivariable logistic regression to explore the associations of individual and grouped KA-7C items with COVID-19 vaccine intention.ResultsAmong 5,234 participants, the vaccine intention model fit (pseudo R-squared values) increased slightly but significantly from 0.62 to 0.65 when adding social conformism and confidence in systems items. Intention to vaccinate was associated with the majority opinion among family and friends (OR: 11.57; 95% confidence interval (CI): 4.51-29.67) and a positive perception of employer's encouragement to get vaccinated (vs negative; OR: 6.41; 95% CI: 3.36-12.22). The strongest association of a knowledge item was identifying the statement 'Some stages of vaccine development (testing) have been skipped because of the epidemic emergency.' as false (OR: 2.36; 95% CI: 1.73-3.22).ConclusionThe results suggest that social conformism and confidence in systems are distinct antecedents of vaccination among healthcare and welfare workers, which should be taken into account in vaccine promotion.

Living conditions, HIV and gender affirmation care pathways of transgender people living with HIV in France: a nationwide, comprehensive, cross-sectional, community-based research protocol (ANRS Trans&HIV).

INTRODUCTION: Transgender identity is poorly accepted in France, and data on living conditions and the daily difficulties transgender people encounter are scarce. This lack of data reinforces their invisibility in social life, contributes to their stigmatisation and probably increases the burden of HIV infection, especially for HIV-positive transgender people (TRHIV). The main objective of the community-based research study ANRS Trans&HIV is to identify personal and social situations of vulnerability in TRHIV, the obstacles they encounter in terms of access to and retention in medical care, and their gender affirmation and HIV care needs. METHODS AND ANALYSIS: ANRS Trans&HIV is a national, comprehensive, cross-sectional survey of all TRHIV currently being followed in HIV care units in France. TRHIV women are exclusively included in the quantitative component, and TRHIV men in the qualitative component. Data are collected by community-based interviewers and will be analysed to explore patient care pathways and living conditions in the TRHIV population with regard to gender affirmation and HIV. Data collection began in October 2020 and should be completed in December 2021. The statistical analyses techniques used will be adapted to each of the study's objectives and to the type of data collected (cross-sectional (questionnaires) and retrospective (biographical trajectory)). The study's results will provide a greater understanding of TRHIV health needs in order to suggest possible national recommendations for comprehensive HIV and gender affirmation medical care. ETHICS AND DISSEMINATION: ANRS Trans&HIV was approved by Inserm's Ethical Evaluation Committee (no 20-694 on 12 May 2020) and is registered with the National Commission on Informatics and Liberty under number 2518030720. Potential participants are informed about the study through an information note provided by their attending HIV physician. All results published in peer-reviewed journals will be disseminated to the HIV transgender community, institutional stakeholders and healthcare providers. TRIAL REGISTRATION NUMBER: NCT04849767.

Management and characteristics of patients suffering from Clostridiodes difficile infection in primary care.

BACKGROUND: Clostridioides difficile infection (CDI) is rising and increases patient healthcare costs due to extended hospitalisation, tests and medications. Management of CDI in French primary care is poorly reported. OBJECTIVES: To characterise patients suffering from CDI, managed in primary care and describe their clinical outcomes. METHODS: Retrospective observational study based on survey data among 500 randomly selected General Practitioners (GPs) surveyed in France from September 2018 to April 2019. GPs were asked to complete a multiple-choice questionnaire for each reported patient presenting a CDI. Responses were analysed according to clinical characteristics. Treatment strategies were compared according to the outcome: recovery or recurrent infection. RESULTS: Participation rate was 8.6% (n = 43/500) with two incomplete questionnaires. Data from 41 patients with an actual diagnosis of CDI were analysed. Recovery was observed in 61% of patients with a confirmed diagnosis of CDI. In the recovery group, this was exclusively a primary episode, most patients (72%) had no comorbidities, were significantly younger (p = 0.02) than the ones who relapsed and 92% were successfully treated with oral metronidazole. Duration of diarrhoea after antimicrobial treatment initiation was significantly shorter in the recovery group (≤ 48 h) (p = 0.03). Cooperation with hospital specialists was reported in 28% of the recovery group versus 87.5% of the recurrent group (p = 0.0003). Overall, GPs managed successfully 82.9% of cases without need of hospital admission. CONCLUSION: GPs provide relevant ambulatory care for mild primary episodes of CDI using oral metronidazole. Persistent diarrhoea despite an appropriate anti-Clostridiodes regimen should be interpreted as an early predictor of relapse.

Factors Associated With Treatment Failure in Moderately Severe Community-Acquired Pneumonia: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Failure of treatment is the most serious complication in community-acquired pneumonia (CAP). Objective: To assess the potential risk factors for treatment failure in clinically stable patients with CAP. Design, Setting, and Participants: This secondary analysis assesses data from a randomized clinical trial on CAP (Pneumonia Short Treatment [PTC] trial) conducted from December 19, 2013, to February 1, 2018. Data analysis was performed from July 18, 2019, to February 15, 2020. Patients hospitalized at 1 of 16 centers in France for moderately severe CAP who were clinically stable at day 3 of antibiotic treatment were included in the PTC trial and analyzed in the per-protocol trial population. Interventions: Patients were randomly assigned (1:1) on day 3 of antibiotic treatment to receive ß-lactam (amoxicillin-clavulanate [1 g/125 mg] 3 times daily) or placebo for 5 extra days. Main Outcomes and Measures: The main outcome was failure at 15 days after first antibiotic intake, defined as a temperature greater than 37.9 °C and/or absence of resolution or improvement of respiratory symptoms and/or additional antibiotic treatment for any cause. The association among demographic characteristics, baseline clinical and biological variables available (ie, at the first day of ß-lactam treatment), and treatment failure at day 15 among the per-protocol trial population was assessed by univariate and multivariable logistic regressions. Results: Overall, 310 patients were included in the study; this secondary analysis comprised 291 patients (174 [59.8%] male; mean [SD] age, 69.6 [18.5] years). The failure rate was 26.8%. Male sex (odds ratio [OR], 1.74; 95% CI, 1.01-3.07), age per year (OR, 1.03; 95% CI, 1.01-1.05), Pneumonia Severe Index score (OR, 1.01; 95% CI, 1.00-1.02), the presence of chronic lung disease (OR, 1.85; 95% CI, 1.03-3.30), and creatinine clearance (OR, 0.99; 95% CI, 0.98-1.00) were significantly associated with failure in the univariate analysis. When the Pneumonia Severe Index score was excluded to avoid collinearity with age and sex in the regression model, only male sex (OR, 1.92; 95% CI, 1.08-3.49) and age (OR, 1.02; 95% CI, 1.00-1.05) were associated with failure in the multivariable analysis. Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, among patients with CAP who reached clinical stability after 3 days of antibiotic treatment, only male sex and age were associated with higher risk of failure, independent of antibiotic treatment duration and biomarker levels. Another randomized clinical trial is needed to evaluate the impact of treatment duration in populations at higher risk for treatment failure.

Discontinuing ß-lactam treatment after 3 days for patients with community-acquired pneumonia in non-critical care wards (PTC): a double-blind, randomised, placebo-controlled, non-inferiority trial.

BACKGROUND: Shortening the duration of antibiotic therapy for patients admitted to hospital with community-acquired pneumonia should help reduce antibiotic consumption and thus bacterial resistance, adverse events, and related costs. We aimed to assess the need for an additional 5-day course of ß-lactam therapy among patients with community-acquired pneumonia who were stable after 3 days of treatment. METHODS: We did this double-blind, randomised, placebo-controlled, non-inferiority trial (the Pneumonia Short Treatment [PTC]) in 16 centres in France. Adult patients (aged ≥18 years) admitted to hospital with moderately severe community-acquired pneumonia (defined as patients admitted to a non-critical care unit) and who met prespecified clinical stability criteria after 3 days of treatment with ß-lactam therapy were randomly assigned (1:1) to receive ß-lactam therapy (oral amoxicillin 1 g plus clavulanate 125 mg three times a day) or matched placebo for 5 extra days. Randomisation was done using a web-based system with permuted blocks with random sizes and stratified by randomisation site and Pneumonia Severity Index score. Participants, clinicians, and study staff were masked to treatment allocation. The primary outcome was cure 15 days after first antibiotic intake, defined by apyrexia (temperature ≤37·8°C), resolution or improvement of respiratory symptoms, and no additional antibiotic treatment for any cause. A non-inferiority margin of 10 percentage points was chosen. The primary outcome was assessed in all patients who were randomly assigned and received any treatment (intention-to-treat [ITT] population) and in all patients who received their assigned treatment (per-protocol population). Safety was assessed in the ITT population. This study is registered with ClinicalTrials.gov, NCT01963442, and is now complete. FINDINGS: Between Dec 19, 2013, and Feb 1, 2018, 706 patients were assessed for eligibility, and after 3 days of ß-lactam treatment, 310 eligible patients were randomly assigned to receive either placebo (n=157) or ß-lactam treatment (n=153). Seven patients withdrew consent before taking any study drug, five in the placebo group and two in the ß-lactam group. In the ITT population, median age was 73·0 years (IQR 57·0-84·0) and 123 (41%) of 303 participants were female. In the ITT analysis, cure at day 15 occurred in 117 (77%) of 152 participants in the placebo group and 102 (68%) of 151 participants in the ß-lactam group (between-group difference of 9·42%, 95% CI -0·38 to 20·04), indicating non-inferiority. In the per-protocol analysis, 113 (78%) of 145 participants in the placebo treatment group and 100 (68%) of 146 participants in the ß-lactam treatment group were cured at day 15 (difference of 9·44% [95% CI -0·15 to 20·34]), indicating non-inferiority. Incidence of adverse events was similar between the treatment groups (22 [14%] of 152 in the placebo group and 29 [19%] of 151 in the ß-lactam group). The most common adverse events were digestive disorders, reported in 17 (11%) of 152 patients in the placebo group and 28 (19%) of 151 patients in the ß-lactam group. By day 30, three (2%) patients had died in the placebo group (one due to bacteraemia due to Staphylococcus aureus, one due to cardiogenic shock after acute pulmonary oedema, and one due to heart failure associated with acute renal failure) and two (1%) in the ß-lactam group (due to pneumonia recurrence and possible acute pulmonary oedema). INTERPRETATION: Among patients admitted to hospital with community-acquired pneumonia who met clinical stability criteria, discontinuing ß-lactam treatment after 3 days was non-inferior to 8 days of treatment. These findings could allow substantial reduction of antibiotic consumption. FUNDING: French Ministry of Health.

The first wave of COVID-19 in hospital staff members of a tertiary care hospital in the greater Paris area: A surveillance and risk factors study.

INTRODUCTION: Understanding how hospital staff members (HSMs), including healthcare workers, acquired severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the first wave can guide the control measures in the current second wave in Europe. METHODS: From March 5 to May 10, 2020, the Raymond-Poincaré Hospital held a weekday consultation for HSMs for PCR testing. HSMs were requested to complete a questionnaire on their potential exposure to SARS-CoV-2. RESULTS: Of 200 HSMs screened, 70 tested positive for SARS-CoV-2. Ninety-nine HSMs completed the questionnaire of whom 28 tested positive for SARS-CoV-2. In the multivariable analysis, age of ≥44 years (aOR = 5.2, 95% CI [1.4-22.5]) and not systematically using a facemask when caring for a patient (aOR = 13.9, 95% CI [1.8-293.0]) were significantly associated with SARS-CoV-2 infection. Working in a COVID-19-dedicated ward (aOR = 0.7, 95% CI [0.2-3.2]) was not significantly associated with infection. Community-related exposure in and outside the hospital, hospital meetings without facemasks (aOR = 21.3, 95% CI [4.5-143.9]) and private gatherings (aOR = 10, 95% CI [1.3-91.0]) were significantly associated with infection. CONCLUSIONS: Our results support the effectiveness of barrier precautions and highlight in-hospital infections not related to patient care and infections related to exposure in the community. Protecting HSMs against COVID-19 is crucial in fighting the second wave of the epidemic.

Quantifying preferences around vaccination against frequent, mild disease with risk for vulnerable persons: A discrete choice experiment among French hospital health care workers.

The individual determinants of vaccine acceptance among health workers (HCWs) have been described in the literature, but there is little evidence regarding the impact of vaccine characteristics and contextual factors (e.g., incentives, communication) on vaccination intentions. We developed a single profile discrete choice experiment (DCE) to assess the impact of seven attributes on stated vaccination intention against an unnamed disease, described as frequent with rapid clinical evolution and epidemic potential (similar to influenza or pertussis). Attributes evaluated vaccine characteristics (effectiveness, security profile), inter-individual aspects (epidemic risk, controversy, potential for indirect protection, vaccine coverage) and incentives (e.g., badge, hierarchical injunction). A total of 1214 French hospital-based HCWs, recruited through professional organizations, completed the online DCE questionnaire. The relative impact of each attribute was estimated using random effects logit models on the whole sample and among specific subgroups. Overall, 52% of included HCWs were vaccinated against influenza during 2017-18 and the average vaccination acceptance rate across all scenarios was 58%. Aside from the management stance, all attributes' levels had significant impact on vaccination decisions. Poor vaccine safety had the most detrimental impact on stated acceptance (OR 0.04 for the level controversy around vaccine safety). The most motivating factor was protection of family (OR 2.41) and contribution to disease control (OR 2.34). Other motivating factors included improved vaccine effectiveness (OR 2.22), high uptake among colleagues (OR 1.89) and epidemic risk declared by health authorities (OR 1.76). Social incentives (e.g., a badge I'm vaccinated) were dissuasive (OR 0.47). Compared to HCWs previously vaccinated against influenza, unvaccinated HCWs who were favorable to vaccination in general were most sensitive towards improved vaccine effectiveness. Our study suggests that vaccine safety considerations dominate vaccine decision-making among French HCWs, while adapted communication on indirect protection and social conformism can contribute to increase vaccination acceptance.

HIV-Sheltering Platelets From Immunological Non-Responders Induce a Dysfunctional Glycolytic CD4+ T-Cell Profile.

Immunological non-responders (InRs) are HIV-infected individuals in whom the administration of combination antiretroviral therapy (cART), although successful in suppressing viral replication, cannot properly reconstitute patient circulating CD4+ T-cell number to immunocompetent levels. The causes for this immunological failure remain elusive, and no therapeutic strategy is available to restore a proper CD4+ T-cell immune response in these individuals. We have recently demonstrated that platelets harboring infectious HIV are a hallmark of InR, and we now report on a causal connection between HIV-containing platelets and T-cell dysfunctions. We show here that in vivo, platelet-T-cell conjugates are more frequent among CD4+ T cells in InRs displaying HIV-containing platelets (<350 CD4+ T cells/µl blood for >1 year) as compared with healthy donors or immunological responders (IRs; >350 CD4+ T cells/µl). This contact between platelet containing HIV and T cell in the conjugates is not infectious for CD4+ T cells, as coculture of platelets from InRs containing HIV with healthy donor CD4+ T cells fails to propagate infection to CD4+ T cells. In contrast, when macrophages are the target of platelets containing HIV from InRs, macrophages become infected. Differential transcriptomic analyses comparing InR and IR CD4+ T cells reveal an upregulation of genes involved in both aerobic and anaerobic glycolysis in CD4+ T cells from InR vs. IR individuals. Accordingly, InR platelets containing HIV induce a dysfunctional increase in glycolysis-mediated energy production in CD4+ T cells as compared with T cells cocultured with IR platelets devoid of virus. In contrast, macrophage metabolism is not affected by platelet contact. Altogether, this brief report demonstrates a direct causal link between presence of HIV in platelets and T-cell dysfunctions typical of InR, contributing to devise a platelet-targeted therapy for improving immune reconstitution in these individuals.

Platelets from HIV-infected individuals on antiretroviral drug therapy with poor CD4+ T cell recovery can harbor replication-competent HIV despite viral suppression.

In addition to hemostasis, human platelets have several immune functions and interact with infectious pathogens including HIV in vitro. Here, we report that platelets from HIV-infected individuals on combined antiretroviral drug therapy (ART) with low blood CD4+ T cell counts (<350 cells/µl) contained replication-competent HIV despite viral suppression. In vitro, human platelets harboring HIV propagated the virus to macrophages, a process that could be prevented with the biologic abciximab, an anti-integrin αIIb/ß3 Fab. Furthermore, in our cohort, 88% of HIV-infected individuals on ART with viral suppression and with platelets containing HIV were poor immunological responders with CD4+ T cell counts remaining below <350 cells/µl for more than one year. Our study suggests that platelets may be transient carriers of HIV and may provide an alternative pathway for HIV dissemination in HIV-infected individuals on ART with viral suppression and poor CD4+ T cell recovery.

Elvitegravir-Cobicistat-Emtricitabine-Tenofovir Alafenamide Single-tablet Regimen for Human Immunodeficiency Virus Postexposure Prophylaxis.

We evaluated an elvitegravir-cobicistat-emtricitabine-tenofovir alafenamide single-tablet regimen for human immunodeficiency virus postexposure prophylaxis. The completion rate and adherence were good, and the tolerance was acceptable; no seroconversion was observed. We confirm that this regimen could be appropriate for postexposure prophylaxis. CLINICAL TRIALS REGISTRATION: NCT02998320.

Impact of a primary care national policy on HIV screening in France: a longitudinal analysis between 2006 and 2013.

BACKGROUND: Early diagnosis of HIV infection is a major public health issue worldwide. In 2009, the French National Authority for Health (Haute Autorité de Santé) developed specific guidelines and recommended mass screening of 15-70-year-olds across the general population. The guidelines were supported by communication directed at healthcare professionals, especially GPs. AIM: To assess the impact of the national mass screening policy on HIV testing. DESIGN AND SETTING: The study used data from the French National Health Insurance Fund database, from January 2006 to December 2013. Males and females aged 15-70 years, excluding HIV-positive individuals and pregnant females, were followed up throughout the 2006-2013 period. During the study period, 2 176 657 person-years and a total of 329 748 different individuals were followed up. METHOD: Standardised and non-standardised rates of HIV screening were calculated for each year; the impact of the policy was assessed using adjusted segmented regression analyses. RESULTS: Overall, annual HIV screening rates increased over the study period, from 4.2% (95% confidence interval [CI] = 4.2 to 4.3) in 2006 to 5.8% (95% CI = 5.7 to 5.9) in 2013 with a more pronounced trend after 2010 (P<0.0001). This increase was more significant for those who regularly consulted a GP. For these individuals, the policy led to a 20.4% increase (95% CI = 17.0 to 23.8) in HIV screening in 2013 compared with only a 4.5% increase (95% CI = 4.4 to 4.5) for those who did not consult a GP regularly in 2013. CONCLUSION: The results show that the mass screening policy coordinated by GPs had a significant impact on HIV testing in France, which could result in positive impacts on public and individual health outcomes.

High efficacy of first-line ART in a West African cohort, assessed by dried blood spot virological and pharmacological measurements.

OBJECTIVES: The objectives of this study were to determine the rate of viral success in HIV-infected patients on first-line ART by the assessment of dried blood spot (DBS) viral load (VL) and to assess the performance of DBS sampling for VL measurement, genotypic resistance and antiretroviral concentration determinations. METHODS: HIV-infected patients treated for >1 year with first-line ART in Niamey, Niger were included. VL based on nucleic acid sequence-based amplification (NASBA) assay (limit of quantification <800 copies/mL) was measured on DBS capillary samples. Resistance genotype was assessed for all detectable VLs (limit of detection >100 copies/mL); antiretroviral concentrations were interpreted using standard plasma cut-offs after extrapolation of blood to plasma results. Median (IQR) results are presented. RESULTS: Two hundred and eighteen patients (61% women), aged 41 (34-46) years, with 138 (56-235) CD4 cells/mm3 at baseline were included. After 4 (2-6) years of follow-up under therapy, CD4 gain was +197 (98-372) cells/mm3; 81% had VL <800 copies/mL. Antiretroviral concentrations were adequate in 87% of patients and nevirapine/efavirenz concentrations were related to viral success (P < 0.001). DBS genotypic resistance amplification succeeded in 71% of failing patients: NRTI drug resistance mutations were identified in 73% including resistance to lamivudine/emtricitabine (67%), abacavir (30%) and tenofovir (21%); and NNRTI drug resistance mutations were identified in 82% including resistance to rilpivirine (39%) and etravirine (15%). CONCLUSIONS: This study demonstrated a good response after 4 years of first-line ART in Niger. Adherence was high, according to antiretroviral concentrations, and the majority of failures were explained by selection of drug resistance mutations detected in the DBS genotype. Using DBS might improve the assessment of ART failure in HIV-infected patients in low-income countries.

Cohort Profile: French hospital database on HIV (FHDH-ANRS CO4).

The French Hospital Database on HIV (FHDH) is a hospital-based multicentre open cohort with inclusions ongoing since 1989. The research objectives focus mainly on mid- and long-term clinical outcomes and therapeutic strategies, as well as severe AIDS and non-AIDS morbidities, and public health issues relative to HIV infection. FHDH also serves to describe HIV-infected patients receiving hospital care in France. FHDH includes data on more than 120,000 HIV-infected patients from 70 French general or university hospitals distributed throughout France. Patients are eligible for inclusion if they are infected by HIV-1 or HIV-2 and give their written informed consent. Standardized variables are collected at each outpatient visit or hospital admission during which a new clinical manifestation is diagnosed, a new treatment is prescribed or a change in biological markers is noted, and/or at least every 6 months. Since its inception, variables collected in FHDH include demographic characteristics, HIV-related biological markers, the date and type of AIDS and non AIDS-defining events, antiretroviral treatments and the date and causes of death, as reported in the medical records. Since 2005, data have also been collected on: co-infection with hepatitis B or C virus; alcohol and tobacco use; and non HIV-related biomarkers. Anyone can submit a research project by completing a standardized form available on the FHDH website (http://www.ccde.fr/_fold/fl-1385734776-429.pdf) or from the corresponding author, describing the context and objectives of the study. All projects are reviewed by the scientific committee.

Impact of late presentation on the risk of death among HIV-infected people in France (2003-2009).

OBJECTIVE: A recent consensus defines "late presentation" (LP) during the course of HIV infection as presentation with AIDS whatever the CD4 cell count or with CD4 <350 cells per cubic millimeter. Here, using this new definition, we examined the frequency and predictors of LP and its impact on mortality. METHODS: In antiretroviral-naive patients enrolled in the French Hospital Database on HIV between 2003 and 2009, we studied risk factors for LP by multivariable logistic regression. The impact of LP on mortality was analyzed according to the level of immunodeficiency by using Cox multivariable models adjusted for potential confounders, with follow-up categorized into 0-6, 6-12, and 12-48 months. RESULTS: There were 11,038 (53.9%) late presenters among the 20,496 patients included in the study. Compared with patients presenting for care with CD4 ≥350 cells per cubic millimeter, patients presenting with AIDS had a very high risk of death with crude hazard ratio ranging from 48.3 during the first 6 months of follow-up to 4.8 during months 12-48; the corresponding values among AIDS-free patients with CD4 ≤200 cells per cubic millimeter were 8.1 and 2.3. Importantly, patients presenting with CD4 between 200 and 350 cells per cubic millimeter also had a significantly increased risk of death beyond 6 months of follow-up (hazard ratio: 3.0 and 1.8 for months 6-12 and 12-48, respectively). Results were similar after adjustment. CONCLUSIONS: LP with HIV infection is still very frequent in France and is associated with higher mortality, even among patients with only moderate immunodeficiency. Encouraging early testing and access to care is still urgently needed.

[Assessing the implementation of the 2010-2014 National Plan against HIV in the Regional Coordination Centers for the Fight against HIV (COREVIHs)]. / Déclinaison du plan national de lutte contre le VIH 2010/2014 au sein des COREVIH.

INTRODUCTION: In France, 50,000 people are unaware of their HIV status because they have not been screened. Every year, there are nearly 7,000 new HIVinfections. To address this issue, the French Ministry of Health and Sport published the 2010-2014 National Plan against HIV/AIDS and other sexually transmitted diseases. A national survey was conducted among the Regional Coordination Centers for the Fight against HIV (COREVIHs) to assess their views of the National Plan and their current funding levels. METHOD: A questionnaire was sent to the presidents and coordinators of the 28 COREVIHs. RESULTS: After two reminders, 19 of the 28 COREVIHs responded. The National Plan was the original impetus for an assessmentofcurrent practices, accompanied by the implementation ofnew measures and new working groups. There is evidence that the COREVIHs are committed to developing incentive measures to promote screening and that they are also working to coordinate regional training programs in the area of screening and testing. The assessment also found that 11 COREVIHs were considering a reorganization of the CDAG/CIDDIST centers (CDAG: Free Anonymous Testing Center/ CIDDIST: STI Information, Testing and Diagnosis Center). Some COREVIHs have been involved in coordinating therapeutic education at a regional level. Most COREVIHs are also actively involved in the fight against discrimination. However, a number of obstacles to the implementation of the plan were identified. DISCUSSION: The purpose of this study was to examine the involvement of the COREVIHs in the implementation of the 2010-2014 National Plan against HIV The results indicate that implementing a system involving a specific form ofregionalcoordination of a public health problem is possible and should provide a basis for the decentralized implementation of public health plans.

[Aging and HIV infection: 4 years follow-up of 149 HIV infected patients older than 60 years in West Paris agglomeration (COREVIH Île-de-France Ouest)]. / Vieillissement et infection par le VIH: suivi de 149 patients âgés de plus de 60ans infectés par le VIH (COREVIH Île-de-France Ouest).

UNLABELLED: In France, patients over 50 years represent more than 23.6% of all registered cases in the French Hospital Database for HIV (FHDH), and 18% of newly HIV-diagnosed patients. OBJECTIVE: To describe the long-term evolution after 4 years of a cohort of HIV infected patients older than 60 years recruited in COREVIH Île-de-France Ouest. RESULTS: One hundred and forty-nine participants, 115 men (77%) and 34 women (23%), were included in the cohort analysis in 2004, and baseline characteristics were: median age 65.4 years (60.3-86.3), CDC stage C: 36%, HBV and HCV co-infections: four (2.7%) and eight (5.4%) patients, median time from first HIV infection diagnosis: 8.5 years (0.25-19.5), ongoing HAART regimen: 88%, median duration of ARV treatment: 7.5 years (0.2-15.5), baseline CD4 cells count: 372/mm(3) (18-1860), HIV viral load less than 200 c/ml: 104 (70%). After a 4-year follow-up, 111 patients were alive, all but one treated with HAART, 17/149 (11.5%) were lost for follow-up, and 21/149 were deceased (14%). Causes of death were acute cardiovascular disease (4/21), neoplasia (11/21), neurological disease 1/21, end stage liver disease 3/21, unknown 2/21. The prevalence of co-morbidities after 4 years of follow-up were: arterial hypertension 40/111 (36%), hypercholesterolemia 48/111 (43%), diabetes 23/111 (21%), kidney disease with renal insufficiency (creatinine clairance<60 ml/min): 36/111 (32%). At the end of follow-up, median CD4 cells count was 494/mm(3), and viral load was undetectable less than 200 c/ml in 107/111 patients (96%). No new opportunistic infection occurred during the 4-year follow-up, but 24 patients had a new diagnosis of neoplasia (incidence 40/1000 person-year). Cancer was the cause of death in 11/24. CONCLUSION: Clinical and immunological improvement was continuous under HAART in these aged HIV infected patients, but co-morbidities are frequently observed in this population, with high incidence of cardiovascular disease and neoplasia, and related mortality. A multidisciplinary approach, with preventive consultations, oncology and cardiovascular screening, as done in geriatrics, is warranted in the aging HIV population.

High number of CD56(bright) NK-cells and persistently low CD4+ T-cells in a hemophiliac HIV/HCV co-infected patient without opportunistic infections.

BACKGROUND: Both the human immunodeficiency virus (HIV) and hepatitis C virus (HCV), either alone or as coinfections, persist in their hosts by destroying and/or escaping immune defenses, with high morbidity as consequence. In some cases, however, a balance between infection and immunity is reached, leading to prolonged asymptomatic periods. We report a case of such an indolent co-infection, which could be explained by the development of a peculiar subset of Natural Killer (NK) cells. RESULTS: Persistently high peripheral levels of CD56+ NK cells were observed in a peculiar hemophiliac HIV/HCV co-infected patient with low CD4 counts, almost undetectable HIV viral load and no opportunistic infections. Thorough analysis of NK-subsets allowed to identify a marked increase in the CD56bright/dim cell ratio and low numbers of CD16+/CD56- cells. These cells have high levels of natural cytotoxicity receptors but low NCR2 and CD69, and lack both CD57 and CD25 expression. The degranulation potential of NK-cells which correlates with target cytolysis was atypically mainly performed by CD56bright NK-cells, whereas no production of interferon γ (IFN-γ) was observed following NK activation by K562 cells. CONCLUSIONS: These data suggest that the expansion and lytic capacity of the CD56bright NK subset may be involved in the protection of this « rare ¼ HIV/HCV co-infected hemophiliac A patient from opportunistic infections and virus-related cancers despite very low CD4+ cell counts.

Risk of Kaposi sarcoma during the first months on combination antiretroviral therapy.

OBJECTIVE: To determine whether incident AIDS-defining Kaposi sarcoma or Pneumocystis jiroveci pneumonia (PJP) is associated with combination antiretroviral therapy (cART) initiation. DESIGN: Compare risk for Kaposi sarcoma and PJP by time on cART and CD4 reconstitution. METHODS: : In the FHDH-ANRS CO4 cohort (N = 66 369), Kaposi sarcoma (N = 1811) and PJP (N = 1718) incidence rates were computed by demographic and HIV strata. Crude and adjusted relative risk (RR) with 95% confidence intervals (CIs) following cART initiation were calculated by Poisson regression with untreated patients during 1996-2009 as reference. CD4 cell counts were compared by Wilcoxon rank sum tests. RESULTS: The risk of Kaposi sarcoma was very high during months 1-3 on cART (N = 160, RRCrude 3.94, 95% CI 3.26-4.76), which was incompletely attenuated by adjustment for demographics and contemporaneous CD4 cell count (RRAdj 1.25, 95% CI 1.02-1.53). Corresponding PJP risk was minimally elevated (N = 84, RRCrude 1.80, 95% CI 1.42-2.30) and markedly reduced with adjustment on the same variables and PJP prophylaxis (RRAdj 0.52, CI 0.41-0.67). HIV load had no added effect. Median CD4 cell count at cART initiation was much lower in patients with incident Kaposi sarcoma (82 cells/µl) or PJP (61 cells/µl) within 3 months than in those who did not develop these conditions (>250 cells/µl). Notably, median CD4 cell count change was +44 cells/µl per month with incident Kaposi sarcoma within 3 months of cART initiation versus 0 cells/µl per month with incident PJP (P = 0.0003). CONCLUSION: Failure of CD4 cell count reconstitution during months 1-3 on cART fully accounted for incident PJP. In contrast, there were 1.6 additional Kaposi sarcoma cases per 1000 person-years during months 1-3 on cART, suggesting that immune reconstitution may contribute to the risk for AIDS-defining Kaposi sarcoma.