Severe Scabies: A French Multi-centre Study Involving 95 Patients with Crusted and Profuse Disease and Review of the Literature.

The aim of this multi-centre French retrospective study was to identify severe, i.e. crusted and profuse, scabies patients. Records were retrieved from 22 Dermatology or Infectious Diseases departments in the Ile-de-France from January 2009 to January 2015 to characterize epidemiology, demography, diagnosis, contributing factors, treatment features, and outcomes in severe scabies. A total of 95 inpatients (57 crusted and 38 profuse) were included. A higher number of cases was observed among elderly patients (>75 years), mostly living in institutions. Thirteen patients (13.6%) reported a history of previously treated scabies. Sixty-three patients (66.3%) had been seen by a previous practitioner for the current episode (up to 8 previous visits). Initial misdiagnosis (e.g. eczema, prurigo, drug-related eruptions, psoriasis) was documented in 41 patients (43.1%). Fifty-eight patients (61%) had already received 1 or more previous treatments for their current episode. Forty percent received corticosteroids or acitretin for an initial diagnosis of eczema or psoriasis. Median time from the onset of symptoms to the diagnosis of severe scabies was 3 months (range 0.3-22). Itch was present in all patients at diagnosis. Most patients (n=84, 88.4%) had comorbidities. Diagnostic and therapeutic approaches varied. Complications occurred in 11.5% of cases. To date, there is no consensus for diagnosis and treatment, and future standardization of is required for optimal management.

Factors Associated With Being Overweight and Obesity in People Living With Human Immunodeficiency Virus on Antiretroviral Therapy: Socioclinical, Inflammation, and Metabolic Markers.

BACKGROUND: We investigated the association between socioclinical, inflammatory, and metabolic markers and weight gain in people with human immunodeficiency virus (HIV) on combination antiretroviral therapy (cART). METHODS: Individuals from the COPANA cohort of normal weight (body mass index [BMI], 18.5-24.9 [ calculated as weight in kilograms divided by height in meters squared) at cART initiation who achieved virological suppression (viral load, <50 copies/mL) and maintained it through 36 months of treatment were selected. Clinical, immunovirological, and socioeconomic data and inflammation (high-sensitivity C-reactive protein, CXCL10, CXCL8, interleukin 6, soluble tumor necrosis factor receptors 1 and 2, soluble CD14, and soluble CD16) and serum metabolic (glucose, insulin, lipid profile, adiponectin, and leptin) markers were assessed. Factors associated with becoming overweight (BMI, 25-29.9) or obese (BMI, ≥30) at 36 months were assessed using multivariate logistic regression models. RESULTS: After 36 months of cART, 32 of 158 people with HIV (20%) became overweight or obese (21% female; 65% born in France and 23% born in sub-Saharan Africa; median BMI at cART initiation, 22 [interquartile range, 21-23]). After adjustment, higher BMI, originating from sub-Saharan Africa, living in a couple, and higher soluble tumor necrosis factor receptor 2 and lower adiponectin concentrations at cART initiation were associated with becoming overweight or obese. CONCLUSION: Weight gain on cART is multifactorial. Special attention should be given to migrants from sub-Saharan Africa. Monocyte activation and adipocyte dysfunction at cART initiation affect weight regulation.

Intravenous Artesunate for the Treatment of Severe Imported Malaria: Implementation, Efficacy, and Safety in 1391 Patients.

BACKGROUND: Intravenous artesunate is the World Health Organization-recommended first-line treatment for severe malaria worldwide, but it is still not fully licensed in Europe. Observational studies documenting its safety and efficacy in imported malaria are thus essential. METHODS: We prospectively collected clinical and epidemiological features of 1391 artesunate-treated patients among 110 participant centers during the first 7 years (2011-2017) of a national program implemented by the French Drug Agency. RESULTS: Artesunate became the most frequent treatment for severe malaria in France, rising from 9.9% in 2011 to 71.4% in 2017. Mortality was estimated at 4.1%. Treatment failure was recorded in 27 patients, but mutations in the Kelch-13 gene were not observed. Main reported adverse events (AEs) were anemia (136 cases), cardiac events (24, including 20 episodes of conduction disorders and/or arrhythmia), and liver enzyme elevation (23). Mortality and AEs were similar in the general population and in people with human immunodeficiency virus, who were overweight, or were pregnant, but the only pregnant woman treated in the first trimester experimented a hemorrhagic miscarriage. The incidence of post-artesunate-delayed hemolysis (PADH) was 42.8% when specifically assessed in a 98-patient subgroup, but was not associated with fatal outcomes or sequelae. PADH was twice as frequent in patients of European compared with African origin. CONCLUSIONS: Artesunate was rapidly deployed and displayed a robust clinical benefit in patients with severe imported malaria, despite a high frequency of mild to moderate PADH. Further explorations in the context of importation should assess outcomes during the first trimester of pregnancy and collect rare but potentially severe cardiac AEs.

Atherosclerotic Cardiovascular Events in Patients Infected With Human Immunodeficiency Virus and Hepatitis C Virus.

BACKGROUND: An increased risk of cardiovascular disease (CVD) was reported in patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV), without identifying factors associated with atherosclerotic CVD (ASCVD) events. METHODS: HIV-HCV coinfected patients were enrolled in the Agence Nationale de Recherches sur le Sida et les hépatites virales (ANRS) CO13 HEPAVIH nationwide cohort. Primary outcome was total ASCVD events. Secondary outcomes were coronary and/or cerebral ASCVD events, and peripheral artery disease (PAD) ASCVD events. Incidences were estimated using the Aalen-Johansen method. Factors associated with ASCVD were identified using cause-specific Cox proportional hazards models. RESULTS: At baseline, median age of the study population (N = 1213) was 45.4 (interquartile range [IQR] 42.1-49.0) years and 70.3% were men. After a median follow-up of 5.1 (IQR 3.9-7.0) years, the incidence was 6.98 (95% confidence interval [CI], 5.19-9.38) per 1000 person-years for total ASCVD events, 4.01 (2.78-6.00) for coronary and/or cerebral events, and 3.17 (2.05-4.92) for PAD ASCVD events. Aging (hazard ratio [HR] 1.06; 95% CI, 1.01-1.12), prior CVD (HR 8.48; 95% CI, 3.14-22.91), high total cholesterol (HR 1.43; 95% CI, 1.11-1.83), high-density lipoprotein cholesterol (HR 0.22; 95% CI, 0.08-0.63), statin use (HR 3.31; 95% CI, 1.31-8.38), and high alcohol intake (HR 3.18; 95% CI, 1.35-7.52) were independently associated with total ASCVD events, whereas undetectable baseline viral load (HR 0.41, 95% CI, 0.18-0.96) was associated with coronary and/or cerebral events. CONCLUSIONS: HIV-HCV coinfected patients experienced a high incidence of ASCVD events. Some traditional cardiovascular risk factors were the main determinants of ASCVD. Controlling cholesterol abnormalities and maintaining undetectable HIV RNA are essential to control cardiovascular risk.

Once-daily etravirine/raltegravir (400/800 mg q24h) dual therapy maintains viral suppression over 48 weeks in HIV-infected patients switching from a twice-daily etravirine/raltegravir (200/400 mg q12h) regimen.

BACKGROUND: Etravirine/raltegravir dual therapy has been shown to be highly effective as a twice-daily (q12h) regimen in suppressed HIV-infected patients enrolled in the ANRS-163 study. OBJECTIVES: As a once-daily (q24h) regimen is easier for daily life, we aimed to evaluate the capacity of etravirine/raltegravir (400/800 mg) q24h to maintain viral suppression in patients on etravirine/raltegravir q12h. METHODS: Patients on a suppressive etravirine/raltegravir q12h regimen for at least 96 weeks were switched to etravirine/raltegravir q24h in this prospective, multicentre, open-label, single-arm study. Primary outcome was the rate of virological failure (VF: confirmed pVL >50 copies/mL, single pVL >400 copies/mL or single pVL >50 copies/mL with ART change) at Week 48 (W48). Secondary outcomes included treatment strategy success rate (no VF and no treatment discontinuation), regimen tolerability, plasma drug concentrations and resistance profile in the case of VF. RESULTS: A total of 111 patients were enrolled, with a median (IQR) age of 57 years (52-62), CD4 count of 710 cells/mm3 (501-919) and viral suppression for 7.9 years (5.9-10.7). Two patients experienced viral rebound at W24 and W48, leading to a VF rate of 2.0% (95% CI 0.5-7.8) at W48, associated with INSTI resistance in one case. Both had past NNRTI mutations. Ten patients discontinued treatment for adverse events (n = 2), investigator or patient decisions (n = 3), lost to follow-up (n = 3), death (n = 1) or pregnancy (n = 1). Overall, the strategy success rate was 89% (95% CI 81.5-93.6) at W48. In a subgroup of 64 patients, median (IQR) plasma C24h concentrations were 401 ng/mL (280-603) for etravirine and 62 ng/mL (31-140) for raltegravir. CONCLUSIONS: Switching patients virally suppressed on etravirine/raltegravir q12h to the same regimen but given q24h was highly effective in maintaining virological suppression in HIV-infected patients.

Severe long-delayed malaria caused by Plasmodium malariae in an elderly French patient.

BACKGROUND: Plasmodium malariae is the cause of the rare but severe form of malaria that sometimes affects individuals travelling to malaria-endemic regions. This report presents the unique case of a patient exhibiting severe malaria symptoms caused by P. malariae with no record of recent travel to any malaria-endemic areas. CASE PRESENTATION: An 81-year-old French woman was admitted to the emergency department with sustained fever and severe weakness for the past 5 days. She suffered from anaemia, thrombocytopenia, confusion, somnolence, pulmonary complications, and hypoxaemia. In the absence of any concrete aetiology that could explain the fever together with thrombocytopenia, physicians suspected malaria as a probable diagnosis. The LAMP-PCR and lateral flow test confirmed the presence of malaria parasite, Plasmodium sp. Microscopic examination (May-Grünwald Giemsa-stained thin blood smear) revealed the presence of trophozoites, schizonts, and gametocytes with 0.93 % parasitaemia. Conventional PCR amplification targeting 510 bp DNA fragment of small subunit ribosomal RNA (ssrRNA) and bidirectional sequencing identified the parasite as Plasmodium malariae. The travel history of this patient revealed her visits to several countries in Europe (Greece), North Africa (Tunisia and Morocco), and the West Indies (Dominican Republic). Of these, the latter was the only country known to be endemic for malaria at the time (three malaria parasite species were prevalent: Plasmodium falciparum, Plasmodium vivax, and P. malariae). The patient had most likely got infected when she visited the Dominican Republic in the summer of 2002. This time interval between the initial parasite infection (2002) till the onset of symptoms and its subsequent diagnosis (2020) is a reminder of the ability of P. malariae to persist in the human host for many years. CONCLUSIONS: This report highlights the persistent nature and ability of P. malariae to cause severe infection in the host even after a prolonged time interval.

Longitudinal study based on a safety registry for malaria patients treated with artenimol-piperaquine in six European countries.

BACKGROUND: European travellers to endemic countries are at risk of malaria and may be affected by a different range of co-morbidities than natives of endemic regions. The safety profile, especially cardiac issues, of artenimol (previously dihydroartemisinin)-piperaquine (APQ) Eurartesim® during treatment of uncomplicated imported falciparum malaria is not adequately described due to the lack of longitudinal studies in this population. The present study was conducted to partially fill this gap. METHODS: Participants were recruited through Health Care Provider's safety registry in 15 centres across 6 European countries in the period 2013-2016. Adverse events (AE) were collected, with a special focus on cardiovascular safety by including electrocardiogram QT intervals evaluated after correction with either Bazett's (QTcB) or Fridericia's (QTcF) methods, at baseline and after treatment. QTcB and/or QTcF prolongation were defined by a value > 450 ms for males and children and > 470 ms for females. RESULTS: Among 294 participants, 30.3% were women, 13.7% of Caucasian origin, 13.5% were current smoker, 13.6% current alcohol consumer and 42.2% declared at least one illness history. The mean (SD) age and body mass index were 39.8 years old (13.2) and 25.9 kg/m2 (4.7). Among them, 75 reported a total of 129 AE (27 serious), 46 being suspected to be related to APQ (11 serious) and mostly labelled as due to haematological, gastrointestinal, or infection. Women and Non-African participants had significantly (p < 0.05) more AEs. Among AEs, 21 were due to cardiotoxicity (7.1%), mostly QT prolongation, while 6 were due to neurotoxicity (2.0%), mostly dizziness. Using QTcF correction, QT prolongation was observed in 17/143 participants (11.9%), only 2 of them reporting QTcF > 500 ms (milliseconds) but no clinical symptoms. Using QTcB correction increases of > 60 ms were present in 9 participants (6.3%). A trend towards increased prolongation was observed in those over 65 years of age but only a few subjects were in this group. No new safety signal was reported. The overall efficacy rate was 255/257 (99.2%). CONCLUSIONS: APQ appears as an effective and well-tolerated drug for treatment of malaria in patients recruited in European countries. AEs and QT prolongation were in the range of those obtained in larger cohorts from endemic countries. Trial registration This study has been registered in EU Post-Authorization Studies Register as EUPAS6942.

The association of metabolic syndrome and COVID-19 deterioration.

BACKGROUND AND AIMS: To evaluate the prevalence and prognostic value of metabolic syndrome (MetS) in patients admitted for coronavirus disease 2019 (COVID-19). METHODS AND RESULTS: In this monocentric cohort retrospective study, we consecutively included all adult patients admitted to COVID-19 units between April 9 and May 29, 2020 and between February 1 and March 26, 2021. MetS was defined when at least three of the following components were met: android obesity, high HbA1c, hypertension, hypertriglyceridemia, and low HDL cholesterol. COVID-19 deterioration was defined as the need for nasal oxygen flow ≥6 L/min within 28 days after admission. We included 155 patients (55.5% men, mean age 61.7 years old, mean body mass index 29.8 kg/m2). Fifty-six patients (36.1%) had COVID-19 deterioration. MetS was present in 126 patients (81.3%) and was associated with COVID-19 deterioration (no-MetS vs MetS: 13.7% and 41.2%, respectively, p < 0.01). Logistic regression taking into account MetS, age, gender, ethnicity, period of inclusion, and Charlson Index showed that COVID-19 deterioration was 5.3 times more likely in MetS patients (95% confidence interval 1.3-20.2) than no-MetS patients. CONCLUSIONS: Over 81.3% of patients hospitalized in COVID-19 units had MetS. This syndrome appears to be an independent risk factor of COVID-19 deterioration.

Spatial determinants of excess all-cause mortality during the first wave of the COVID-19 epidemic in France.

BACKGROUND: The first wave of the COVID-19 pandemic in France was associated with high excess mortality, and anecdotal evidence pointed to differing excess mortality patterns depending on social and environmental determinants. In this study we aimed to investigate the spatial distribution of excess mortality during the first wave of the COVID-19 pandemic in France and relate it at the subnational level to contextual determinants from various dimensions (socioeconomic, population density, overall health status, healthcare access etc.). We also explored whether the determinants identified at the national level varied depending on geographical location. METHODS: We used available national data on deaths in France to calculate excess mortality by department for three age groups: 0-49, 50-74 and > 74 yrs. between March 1st and April 27th, 2020. We selected 15 variables at the department level that represent four dimensions that may be related to overall mortality at the ecological level, two representing population-level vulnerabilities (morbidity, social deprivation) and two representing environmental-level vulnerabilities (primary healthcare supply, urbanization). We modelled excess mortality by age group for our contextual variables at the department level. We conducted both a global (i.e., country-wide) analysis and a multiscale geographically weighted regression (MGWR) model to account for the spatial variations in excess mortality. RESULTS: In both age groups, excess all-cause mortality was significantly higher in departments where urbanization was higher (50-74 yrs.: ß = 15.33, p < 0.001; > 74 yrs.: ß = 18.24, p < 0.001) and the supply of primary healthcare providers lower (50-74 yrs.: ß = - 8.10, p < 0.001; > 74 yrs.: ß = - 8.27, p < 0.001). In the 50-74 yrs. age group, excess mortality was negatively associated with the supply of pharmacists (ß = - 3.70, p < 0.02) and positively associated with work-related mobility (ß = 4.62, p < 0.003); in the > 74 yrs. age group our measures of deprivation (ß = 15.46, p < 0.05) and morbidity (ß = 0.79, p < 0.008) were associated with excess mortality. Associations between excess mortality and contextual variables varied significantly across departments for both age groups. CONCLUSIONS: Public health strategies aiming at mitigating the effects of future epidemics should consider all dimensions involved to develop efficient and locally tailored policies within the context of an evolving, socially and spatially complex situation.

Imported loiasis in France: a retrospective analysis of 167 cases with comparison between sub-Saharan and non sub-Saharan African patients.

BACKGROUND: Imported loiasis is a rare cause of consultation at the return of stay in central Africa, which often poses difficult diagnostic and therapeutic questions to practitioners especially those who are unaccustomed to tropical medicine. These difficulties can lead to risks for the patients especially if inappropriate treatment is given. Large series of imported loiasis are scarce. METHODS: We retrospectively studied the data including outcome in patients diagnosed with imported loiasis between 1993 and 2013 in the Paris area on the basis of a parasitological diagnosis (microfilaremia > 1/ml and/or serologic tests). We compared sub-Saharan and non sub-Saharan African patients. RESULTS: Of the 177 identified cases, 167 could be analysed. Sex ratio was 1, mean age 41 years and 83% were sub-Saharan Africans. Cameroon was the main country of exposure (62%). Incubation time may be long (up to 18 months). Of the 167 cases, 57% presented with characteristic symptoms (Calabar swellings, creeping dermatitis, eyeworm) whereas 43% were diagnosed fortuitously. Microfilaremia was evidenced in 105 patients (63%), and specific antibodies in 53%. Compared to sub-Saharan Africans, other patients were presenting less frequently with eyeworm migration and microfilaremia whereas they had higher eosinophilia and positive serology. Prevalence of Calabar swellings was not significantly different between the two groups. Cure rates were 52% with ivermectin alone, and 77% with ivermectin followed by diethylcarbamazine. No severe adverse event was reported. CONCLUSIONS: Presentation of imported loiasis varies according to ethnicity. A systematic screening should be recommended in patients with potential exposure in endemic country. Treatment with ivermectin followed by diethylcarbamazine could be a valuable option.

Dual therapy combining raltegravir with etravirine maintains a high level of viral suppression over 96 weeks in long-term experienced HIV-infected individuals over 45 years on a PI-based regimen: results from the Phase II ANRS 163 ETRAL study.

BACKGROUND: Dual therapy combining integrase inhibitors and NNRTIs represents a promising regimen in ageing HIV-infected individuals with long exposure to nucleoside analogues and PIs. METHODS: The ANRS 163 ETRAL trial (NCT02212379) was a 96 week, multicentre, single-arm study evaluating the efficacy and safety of raltegravir (400 mg twice daily)/etravirine (200 mg twice daily) in individuals >45 years, on a PI-containing regimen who were integrase inhibitor and etravirine naive. The primary endpoint was the proportion of participants with virological success, defined by the absence of virological failure up to week 48. Main secondary outcomes included evolution of metabolic parameters, CD4/CD8 count, bone mineral density and inflammatory markers. The study was designed to show an efficacy >90%, assuming a success rate ≥95%, with a power of 80% and a 5% type-1 error. RESULTS: One hundred and sixty-five participants (median age 52 years, duration of ART 16.9 years, viral suppression 6.9 years and CD4 count 700 cells/mm3) were enrolled. By ITT analysis, viral suppression was maintained in 99.4% of participants (95% CI = 95.6%-99.9%) at week 48 and 98.7% (95% CI = 95.0%-99.7%) at week 96. Two virological failures occurred (week 24 and week 64) without emergence of integrase inhibitor resistance. Eight participants discontinued raltegravir/etravirine for adverse events, leading to a strategy success rate of 95.1% (95% CI = 90.5%-97.5%) at week 48 and 92.7% (95% CI = 87.5%-95.8%) at week 96. Over 96 weeks, lipid fractions improved (P < 0.001), CD4/CD8 ratio increased, IFNγ-induced protein 10 (IP-10) decreased (-8.1%), soluble CD14 decreased (-27%, P < 0.001) bone mineral density improved and BMI increased. CONCLUSIONS: Raltegravir plus etravirine dual therapy demonstrated durable efficacy in virologically suppressed ageing patients.

Plasmodium vivax severe imported malaria in two migrants in France.

BACKGROUND: With less than one severe case per year in average, Plasmodium vivax is very rarely associated with severe imported malaria in France. Two cases of P. vivax severe malaria occurred in patients with no evident co-morbidity. Interestingly, both cases did not occur at the primary infection but during relapses. CASE PRESENTATIONS: Patient 1: A 27-year old male, born in Afghanistan and living in France since 2012, was admitted on August 2015 to the Avicenne hospital because of abdominal pain, intense headache, fever and hypotension. The patient was haemodynamically unstable despite 5 L of filling solution. A thin blood film showed P. vivax trophozoites within the red blood cells. To take care of the septic shock, the patient was given rapid fluid resuscitation, norepinephrine (0.5 mg/h), and intravenous artesunate. Nested polymerase chain reactions of the SSUrRNA gene were negative for Plasmodium falciparum but positive for P. vivax. The patient became apyretic in less than 24H and the parasitaemia was negative at the same time. Patient 2: A 24-year old male, born in Pakistan and living in France, was admitted on August 2016 because of fever, abdominal pain, headache, myalgia, and nausea. The last travel of the patient in a malaria endemic area occurred in 2013. A thin blood film showed P. vivax trophozoites within the red blood cells. The patient was treated orally by dihydroartemisinin-piperaquine and recovered rapidly. Nine months later, the patient returned to the hospital with a relapse of P. vivax malaria. The malaria episode was uncomplicated and the patient recovered rapidly. Three months later, the patient came back again with a third episode of P. vivax malaria. Following a rapid haemodynamic deterioration, the patient was transferred to the intensive care unit of the hospital. In all the patient received 10 L of filling solution to manage the septic shock. After 5 days of hospitalization and a specific treatment, the patient was discharged in good clinical conditions. CONCLUSION: Clinicians should be aware of the potential severe complications associated with P. vivax in imported malaria, even though the primary infection is uncomplicated.

Artenimol-piperaquine in children with uncomplicated imported falciparum malaria: experience from a prospective cohort.

BACKGROUND: Although malaria remains one of the major public health threats in inter-tropical areas, there is limited understanding of imported malaria in children by paediatricians and emergency practitioners in non-endemic countries, often resulting in misdiagnosis and inadequate treatment. Moreover, classical treatments (atovaquone-proguanil, quinine, mefloquine) are limited either by lengthy treatment courses or by side effects. Since 2010, the World Health Organization (WHO) has recommended the use of oral artemisinin-based combination therapy for the treatment of uncomplicated Plasmodium falciparum malaria worldwide. The benefits of artenimol-piperaquine in children have been validated in endemic countries but experience remains limited in cases of imported malaria. METHODS: This prospective observational study in routine paediatric care took place at the Emergency Department, Robert-Debré Hospital (Paris, France) from September 2012 to December 2014. Tolerance and efficacy of artenimol-piperaquine in children presenting with the following inclusion criteria were assessed: P. falciparum positive on thin or thick blood smear; and the absence of WHO-defined features of severity. RESULTS: Among 83 children included in this study, treatment with artenimol-piperaquine was successful in 82 children (98.8%). None of the adverse events were severe and all were considered mild with no significant clinical impact. This also applied to cardiological adverse events despite a significant increase of the mean post-treatment QTc interval. CONCLUSION: Artenimol-piperaquine displays a satisfying efficacy and tolerance profile as a first-line treatment for children with imported uncomplicated falciparum malaria and only necessitates three once-daily oral intakes of the medication. Comparative studies versus artemether-lumefantrine or atovaquone-proguanil would be useful to confirm the results of this study.

Social and structural factors and engagement in HIV care of sub-Saharan African migrants diagnosed with HIV in the Paris region.

Migrants from sub-Saharan Africa (SSA) are often diagnosed at an advanced stage of HIV, and many of them have harsh living conditions. We aimed to evaluate the entry into care after HIV diagnosis and examine the related social determinants. The ANRS PARCOURS study is a life-event survey conducted in 2012-2013 in the Paris region among. Time between HIV diagnosis of SSA migrants living diagnosed HIV positive in France and HIV care and the determinants was assessed yearly by using mixed-effects logistic regression models. Among a total of 792 participants, 94.2% engaged in HIV care within the year of HIV diagnosis, 4.3% in the following year and 2.5% beyond the second year after diagnosis. The participants were more likely to engage in HIV care during years when they were effectively covered by health insurance and if the HIV test was carried out at the initiative of the doctor. Immigration for economic reasons or owing to threats in his/her country of origin was associated with delayed engagement in HIV care. Additionally, 4.3% of treated participants discontinued HIV care at least once at the time of the survey and more often if diagnosed at an advanced HIV disease stage and financially dependent.

[Malaria prevention]. / Prévention du paludisme.

Malaria prevention. Due to the huge difference in risk of infection between tropical Asia and America on the one hand and sub-saharan Africa on the other (ratio of 1 to 1000) and lack of transmission of Plasmodium falciparum in Asia and tropical America, it is now recommended to no longer prescribe chemoprophylaxis in these low-risk areas in the vast majority of cases (conventional stays), retaining the simple adage: Sub-Saharan Africa yes, elsewhere no ! In any case, travelers should be advised to limit the mosquito bites at night (especially repellents but also mosquito nets impregnated and impregnation of clothing) and to signal the tropical stay in case of fever at the return. African migrants being the main target of imported malaria should be informed of the importance of this prevention.

Prévention du paludisme. En raison de l'énorme différence de risque d'infection entre l'Asie et l'Amérique tropicales d'une part et l'Afrique subsaharienne d'autre part (rapport de 1 à 1 000) et de l'absence de transmission urbaine de Plasmodium falciparum en Asie et Amérique tropicales, il est licite maintenant de ne plus prescrire de chimioprophylaxie dans ces zones à faible risque dans la grande majorité des cas (séjours conventionnels) en retenant l'adage simple : Afrique subsaharienne oui, ailleurs non ! Dans tous les cas, on recommande aux voyageurs de limiter les piqûres de moustiques la nuit (répulsifs surtout mais aussi moustiquaires imprégnées et imprégnation des vêtements) et de bien signaler le séjour tropical en cas de fièvre au retour. Les migrants africains étant la cible principale du paludisme d'importation doivent être informés de l'importance de cette prévention.

Week 96 efficacy of lopinavir/ritonavir monotherapy in virologically suppressed patients with HIV: a randomized non-inferiority trial (ANRS 140 DREAM).

Background: Sparing of antiretroviral drug classes could reduce the toxicity and cost of maintenance treatment for HIV infection. Objectives: To evaluate the non-inferiority of efficacy and the safety of lopinavir/ritonavir (r) monotherapy versus a single-tablet regimen of efavirenz, emtricitabine and tenofovir (EFV/FTC/TDF) over 2 years. Methods: Adults on stable ART with plasma HIV-1 RNA viral load <50 copies/mL for the past 12 months and no documented treatment failure were randomized to receive either lopinavir/r or EFV/FTC/TDF for 2 years. The primary endpoint was the proportion of patients without treatment failure at week 96 (viral load <50 copies/mL at week 96, confirmed at week 98), without study treatment discontinuation, a new AIDS-defining illness, or death. Results: In the ITT analysis, the primary endpoint was reached by, respectively, 64% and 71% of patients in the lopinavir/r (n = 98) and EFV/FTC/TDF arms (n = 97), yielding a difference of -6.8% (lower limit of the 95% two-sided CI: -19.9%). Sanger and UltraDeep sequencing showed the occurrence of PI mutations in the lopinavir/r arm (n = 4) and of NNRTI and/or NRTI mutations in the EFV/FTC/TDF arm (n = 2). No unexpected serious clinical events occurred. Conclusions: Lopinavir/r monotherapy cannot be considered non-inferior to EFV/FTC/TDF. PI resistance rarely emerged in the lopinavir/r arm and did not undermine future PI options. Two years of lopinavir/r monotherapy had no deleterious clinical impact when compared with EFV/FTC/TDF.

Four-days-a-week antiretroviral maintenance therapy in virologically controlled HIV-1-infected adults: the ANRS 162-4D trial.

Background: Intermittent treatment could improve the convenience, tolerability and cost of ART, as well as patients' quality of life. We conducted a 48 week multicentre study of a 4-days-a-week antiretroviral regimen in adults with controlled HIV-1-RNA plasma viral load (VL). Methods: Eligible patients were adults with VL < 50 copies/mL for at least 1 year on triple therapy with a ritonavir-boosted PI (PI/r) or an NNRTI. The study protocol consisted of the same regimen taken on four consecutive days per week followed by a 3 day drug interruption. The primary outcome was the proportion of participants remaining in the strategy with VL < 50 copies/mL up to week 48. The study was designed to show an observed success rate of > 90%, with a power of 87% and a 5% type 1 error. The study was registered with ClinicalTrials.gov (NCT02157311) and EudraCT (2014-000146-29). Results: One hundred patients (82 men), median age 47 years (IQR 40-53), were included. They had been receiving ART for a median of 5.1 (IQR 2.9-9.3) years and had a median CD4 cell count of 665 (IQR 543-829) cells/mm3. The ongoing regimen included PI/r in 29 cases and NNRTI in 71 cases. At 48 weeks, 96% of participants (95% CI 90%-98%) had no failure while remaining on the 4-days-a-week regimen. Virological failure occurred in three participants, who all resumed daily treatment and became resuppressed. One participant stopped the strategy. No severe treatment-related events occurred. Conclusions: Antiretroviral maintenance therapy 4 days a week was effective for 48 weeks in 96% of patients, leading to potential reduction of long-term toxicities, high adherence to the antiretroviral regimen and drug cost saving.

Refusal to provide healthcare to sub-Saharan migrants in France: a comparison according to their HIV and HBV status.

Background: In this study, we aim to measure and compare the frequency of reported denial of care in sub-Saharan African migrants living in the Paris area, according to their HIV and HBV status and social and migration characteristics. Methods: The ANRS-PARCOURS study is a life-event survey conducted in 2012-13 in healthcare facilities in the Paris area, among three groups of sub-Saharan migrants recruited in primary care centres (N = 760; reference group), in dedicated centres for HIV care (N = 922; HIV group) and in centres for chronic hepatitis B care (N = 777; CHB group). Characteristics associated with refusal of care since arrival in France were identified using a logistic regression model. Results: Compared to the reference group (6%, P < 0.001), the reported refusal of care was twice as high in the HIV group (12%) and the CHB group (10%). In the multivariate analysis, men and women living with HIV were at greater risk of being denied care (aOR = 2.20[1.14-4.25] and 2.24[1.25-4.01]). Women covered by the specific health insurance (HI) for precarious or undocumented migrants were also at higher risk (aOR = 2.07[1.10-3.89] and 2.69[1.18-6.10], respectively). The risk was also increased in men who remained for at least one year without permit of residence or without HI and among those who were threatened in their country. Conclusion: Refusals to provide healthcare are frequent and deleterious situations especially for migrants living with HIV. Health decision makers, public insurance bodies and health professional councils must address this issue to improve equity in the healthcare system.

Efficacy and safety of direct-acting antiviral regimens in HIV/HCV-co-infected patients - French ANRS CO13 HEPAVIH cohort.

BACKGROUND & AIMS: There is little data available on the use of new oral direct-acting antiviral (DAA) regimens to treat human immunodeficiency virus and hepatitis C virus (HIV/HCV) co-infected patients in real-life settings. Here, the efficacy and safety of all-oral DAA-based regimens in HIV/HCV-co-infected patients enrolled in the French nationwide ANRS CO13 HEPAVIH observational cohort are reported. METHODS: HIV/HCV-co-infected patients enrolled in the ANRS CO13 HEPAVIH observational cohort were included if they began an all-oral DAA-based regimen before 1st May 2015 (12-week regimens) or 1st February 2015 (24-week regimens). Treatment success (SVR12) was defined by undetectable HCV-RNA 12weeks after treatment cessation. Exact logistic regression analysis was used to identify factors associated with SVR12. RESULTS: A total of 323 patients (74% men) with a median age of 53years were included, 99% of whom were on combination antiretroviral therapy (cART). HIV RNA load was <50 copies/ml in 88% of patients; median CD4 cell count was 540/mm3; 60% of patients were cirrhotic; 68% had previously received unsuccessful anti-HCV treatment. cART was protease inhibitor (PI)-based in 23%, non-nucleoside reverse transcriptase inhibitor (NNRTI)-based in 15%, and integrase inhibitor (II)-based in 38%, while 24% of patients received other regimens. The SVR12 rate was 93.5% overall (95% confidence interval [CI]: 90.2-95.9), 93.3% (88.8-96.4) in patients with cirrhosis and 93.8% (88.1-97.3) in patients without cirrhosis. The SVR12 rates were 93.1% (84.5-97.7), 91.8% (80.4-97.7) and 95.8% (90.5-98.6) respectively, in patients receiving PI-based, NNRTI-based and II-based cART. In adjusted analysis, SVR12 was not associated with HIV RNA load, the cART regimen, cirrhosis, prior anti-HCV treatment, the duration of anti-HCV therapy, or ribavirin use. The most common adverse effects were fatigue and digestive disorders. CONCLUSIONS: New all-oral DAA regimens were well-tolerated and yielded high SVR12 rates in HIV/HCV-co-infected patients. LAY SUMMARY: We evaluated efficacy and safety of all-oral DAA regimens in a large French nationwide observational cohort study of HIV/HCV co-infected patients. Sustained virological response 12weeks after treatment cessation was 93.5% overall. The all-oral DAA regimens were well-tolerated and most common adverse effects were fatigue and digestive disorders.