High-flow cannula for frail patients with SARS-CoV-2 infection non-eligible for intensive care unit management.

OBJECTIVES: High-flow nasal cannula (HFNC) was widely used during the COVID-19 pandemic in intensive care units (ICU), but there is no recommendation for elderly patients non-eligible for ICU management. We aimed to describe the outcomes of HFNC treatment in patients with COVID-19 who are not eligible for ICU management. METHODS: Retrospective bicentric cohort study performed between September 1, 2020 and June 30, 2021 in two infectious diseases departments of Colmar Hospital and Antoine Beclere University Hospital, France. RESULTS: Sixty-four patients were treated with HFNC: 33 in Colmar and 31 in Beclere hospital (median age: 85 years; IQ, 82-92). Of these, 16 patients survived (25%). Surviving patients had a lower Charlson comorbidity index score than deceased patients (five vs six; p = 0.02). CONCLUSIONS: Despite a high death rate, with survivors being younger and having fewer comorbidities, HFNC is an easy tool to implement in non-ICU wards for the frailest patients.

Factors associated with hospital admission and adverse outcome for COVID-19: Role of social factors and medical care.

BACKGROUND: Beyond sex, age, and various comorbidities, geographical origin and socioeconomic deprivation are associated with Coronavirus Disease (COVID-19) morbidity and mortality in the general population. We aimed to assess factors associated with severe forms of COVID-19 after a hospital emergency department visit, focusing on socioeconomic factors. METHODS: Patients with laboratory-confirmed COVID-19 attending the emergency department of Béclère Hospital (France) in March-April 2020 were included. Postal addresses were used to obtain two geographical deprivation indices at the neighborhood level. Factors associated with hospitalization and factors associated with adverse outcomes, i.e. mechanical ventilation or death, were studied using logistic and Cox analyses, respectively. RESULTS: Among 399 included patients, 321 were hospitalized. Neither geographical origin nor socioeconomic deprivation was associated with any of the outcomes. Being male, older, overweight or obese, diabetic, or having a neuropsychiatric disorder were independent risk factors for hospitalization. Among 296 patients hospitalized at Béclère Hospital, 91 experienced an adverse outcome. Older age, being overweight or obese, desaturation and extent of chest CT scan lesions>25% at admission (aHR: 2.2 [95% CI: 1.3-3.5]) and higher peak CRP levels and acute kidney failure (aHR: 2.0 [1.2-3.3]) during follow-up were independently associated with adverse outcomes, whereas treatment with hydrocortisone reduced the risk of mechanical ventilation or death by half (aHR: 0.5 [0.3-0.8]). CONCLUSION: No association between geographical origin or socioeconomic deprivation and the occurrence of a severe form of COVID-19 was observed in our population after arrival to the emergency department. Empirical corticosteroid use with hydrocortisone had a strong protective impact.

Does region of origin influence the timing and outcome of first-line antiretroviral therapy in France?

OBJECTIVES: The aim of the study was to assess whether the timing of combination antiretroviral therapy (cART) initiation, the choice of cART and virological response differ in migrants versus European natives in the north and east of Paris area, after dissemination of French recommendations for universal treatment. METHODS: Antiretroviral therapy-naïve HIV-1-infected adults with at least two follow-up visits at one of 15 participating centres between 1 January 2014 and 31 March 2015 were included in the study. Factors associated with cART initiation before 31 March 2015, with protease inhibitor (PI)-containing cART among individuals initiating cART, and with 1-year virological success after cART initiation were assessed using multivariable logistic regression models. Sex, age, region of origin [Western Europe, sub-Saharan Africa (SSA) or other], HIV transmission group, baseline AIDS status, CD4 cell count and plasma viral load (VL), and hepatitis B and/or C virus infection were considered in the analyses. RESULTS: Among 912 individuals, only 584 (64%) started cART during the study period. After adjustment, migrants from SSA were half as likely to initiate cART and to have a subsequent virological response compared with individuals from Western Europe [adjusted odds ratio (aOR) 0.54; 95% confidence interval (CI) 0.36-0.82; and aOR 0.52; 95% CI 0.28-0.98, respectively]. PI-containing cART was more frequently prescribed in migrants from SSA, in people with lower CD4 cell counts and in people with higher VL. CONCLUSIONS: Even in the context of universal cART recommendations and of free access to care, migrants from SSA still have delayed access to cART and a lower virological response. Efforts are still necessary to provide immediate cART to all people living with HIV.

Risk factors for loss to follow-up, transfer or death among people living with HIV on their first antiretroviral therapy regimen in Mali.

OBJECTIVES: Risk factors for loss to follow-up (LTFU) were assessed for people living with HIV (PLHIV) at various reference out-patient clinics (expertise level II) and hospitals (expertise level III) in Mali. METHODS: HIV-1-positive adults starting antiretroviral therapy (ART) in 2006-2013 were eligible for inclusion. Risk factors for LTFU, defined as no visit in the 6 months preceding the last database update, were assessed with the Cox model, taking into account the competing risks of transfer and death. Potential risk factors at the start of ART were demographic and socioeconomic variables, World Health Organization (WHO) stage, CD4 count, period of ART initiation, type of ART, region of care, expertise level and distance from home. RESULTS: We included 9821 PLHIV, 33% of whom were male, starting ART at nine out-patient clinics and seven hospitals [five and two in the capital Bamako and four and five in the 'regions' (i.e. districts outside the capital), respectively] with a median (interquartile range) CD4 count of 153 (56-270) cells/µL. Five-year cumulative incidences of LTFU, transfer and death were 35.2, 9.7 and 6.7%, respectively. People followed at Bamako hospitals > 5 km from home, at regional hospitals or at regional out-patient clinics < 5 km from home were at higher risk of LTFU than people followed at Bamako out-patient clinics, whereas people followed at regional out-patient clinics 5-50 km away from home were at lower risk for LTFU. Deaths were less frequent at hospitals, whether in Bamako or in the regions, than at Bamako out-patient clinics, and more frequent at regional out-patient clinics. CONCLUSIONS: Expertise level and distance to care were associated with LTFU. Stigmatization may play a role for PLHIV living close to the centres in the regions.

Factors Associated with HIV Status Disclosure in HIV-Infected Sub-Saharan Migrants Living in France and Successfully Treated with Antiretroviral Therapy: Results from the ANRS-VIHVO Study.

To estimate rates and identify correlates of HIV disclosure in migrants from sub-Saharan Africa (SSA) successfully treated, a sub-analysis was conducted in HIV-1 native SSA migrants, living in France with undetectable viral load on antiretroviral, included in the VIHVO adherence study. Logistic regression models assessed factors associated with HIV disclosure. Among 246 individuals (40 % male, median age 41), 79 % of those in a steady heterosexual partnership (n = 167) had disclosed their status to their partner, 55 % of the total 246 to a relative, and 33 % to (an)other person(s). Disclosure to one's steady partner was associated with a follow-up duration since HIV diagnosis of more than 5 years, a higher literacy level, a better social context and marital status. Women were more likely to disclose their HIV status to relatives. Interventions targeting this population should be provided to improve disclosure which in turn ensures better social support, testing of the partner and lower rates of undiagnosed HIV.

Lack of effect of doxycycline on trough concentrations of protease inhibitors or non-nucleoside reverse transcriptase inhibitors in HIV-infected patients.

BACKGROUND: Many HIV-treated patients travel to malaria-infected zones, but very few data are available on potential interactions between antiretroviral and antimalarial drugs. METHOD: We performed a pharmacokinetic study on the interaction of doxycycline (100 mg/d) on 2 protease inhibitors (PIs), atazanavir and lopinavir, and 2 non-nucleoside reverse transcriptase inhibitors (NNRTIs), efavirenz and nevirapine, given at usual daily doses in HIV-infected migrants native from sub-Saharan Africa included in the VIHVO ANRS-study before travelling to a sub-Saharan country. Antiretroviral trough plasma concentrations were measured at enrollment visit during the month preceding the travel before doxycycline introduction and on the week following the patients' return to France when they had been taking doxycycline for at least 15 days. Impact of doxycycline on antiretroviral concentrations was tested either with antiretroviral drugs separately or within the therapeutic classes (PI or NNRTI) in patients with an HIV RNA level <50 copies/mL at both visits and with good declared adherence. The Two One-Sided Test that was adapted to the Wilcoxon test was used to evidence the lack of interaction. Sixty-five patients receiving regimens containing atazanavir (n = 1), ritonavir-boosted atazanavir (n = 14), ritonavir-boosted lopinavir (n = 23), efavirenz (n = 17), nevirapine (n = 10) were included. RESULTS: Lack of pharmacokinetic interaction was statistically significant when tested by therapeutic class (PI, P = .02; NNRTI, P = .005) and was not demonstrated for each antiretroviral when tested separately. CONCLUSION: This study is the first to assess the interaction of doxycycline on PI and NNRTI. This lack of pharmacokinetic interaction supports the choice of doxycycline as the antimalarial drug in patients treated with PI or NNRTI.

The incidence of AIDS-defining illnesses at a current CD4 count ≥ 200 cells/µL in the post-combination antiretroviral therapy era.

BACKGROUND: Few studies consider the incidence of individual AIDS-defining illnesses (ADIs) at higher CD4 counts, relevant on a population level for monitoring and resource allocation. METHODS: Individuals from the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) aged ≥14 years with ≥1 CD4 count of ≥200 µL between 1998 and 2010 were included. Incidence rates (per 1000 person-years of follow-up [PYFU]) were calculated for each ADI within different CD4 strata; Poisson regression, using generalized estimating equations and robust standard errors, was used to model rates of ADIs with current CD4 ≥500/µL. RESULTS: A total of 12 135 ADIs occurred at a CD4 count of ≥200 cells/µL among 207 539 persons with 1 154 803 PYFU. Incidence rates declined from 20.5 per 1000 PYFU (95% confidence interval [CI], 20.0-21.1 per 1000 PYFU) with current CD4 200-349 cells/µL to 4.1 per 1000 PYFU (95% CI, 3.6-4.6 per 1000 PYFU) with current CD4 ≥ 1000 cells/µL. Persons with a current CD4 of 500-749 cells/µL had a significantly higher rate of ADIs (adjusted incidence rate ratio [aIRR], 1.20; 95% CI, 1.10-1.32), whereas those with a current CD4 of ≥1000 cells/µL had a similar rate (aIRR, 0.92; 95% CI, .79-1.07), compared to a current CD4 of 750-999 cells/µL. Results were consistent in persons with high or low viral load. Findings were stronger for malignant ADIs (aIRR, 1.52; 95% CI, 1.25-1.86) than for nonmalignant ADIs (aIRR, 1.12; 95% CI, 1.01-1.25), comparing persons with a current CD4 of 500-749 cells/µL to 750-999 cells/µL. DISCUSSION: The incidence of ADIs was higher in individuals with a current CD4 count of 500-749 cells/µL compared to those with a CD4 count of 750-999 cells/µL, but did not decrease further at higher CD4 counts. Results were similar in patients virologically suppressed on combination antiretroviral therapy, suggesting that immune reconstitution is not complete until the CD4 increases to >750 cells/µL.

Treatment for tuberculosis-associated immune reconstitution inflammatory syndrome in 34 HIV-infected patients.

BACKGROUND: Paradoxical tuberculosis immune reconstitution inflammatory syndrome (TB-IRIS) frequently follows the initiation of antiretroviral therapy (ART) in patients with tuberculosis (TB) and human immunodeficiency virus (HIV) co-infection. Treatment recommendations are nearly exclusively based on expert opinion. OBJECTIVE: To assess the clinical outcomes of patients treated using various strategies for TB-IRIS. METHODS: In a retrospective analysis of patients treated in Paris hospitals from 1996 to 2008, we describe TB-IRIS outcome, frequency of relapses and CD4 cell count changes after 12 months of ART for the following strategies: no treatment, interrupted ART and use of steroids. RESULT: Among 34 patients, TB-IRIS outcome was favourable in 10/10 with no treatment, 11/13 with ART interruption, 3/3 with ART interruption and simultaneous use of steroids and 8/8 with steroids alone. Relapses were observed in both the ART interruption (6/13, 46%) and steroids (4/8, 50%) groups, but were less frequent in the no-treatment group (1/10, 10%). Steroids were prescribed in 61% of the patients and had no significant side effects; steroid use was associated with a trend towards a lower median CD4 cell count at 12 months of ART compared to the others (230 vs. 322 cells/mm(3)), despite no baseline differences. CONCLUSION: TB-IRIS outcome was favourable regardless of the therapeutic strategies employed. Although steroids were widely used and well-tolerated, an initial wait-and-see attitude in the case of non-severe IRIS remains an interesting strategy to be evaluated.

The effect of injecting drug use history on disease progression and death among HIV-positive individuals initiating combination antiretroviral therapy: collaborative cohort analysis.

BACKGROUND: We examined whether determinants of disease progression and causes of death differ between injecting drug users (IDUs) and non-IDUs who initiate combination antiretroviral therapy (cART). METHODS: The ART Cohort Collaboration combines data from participating cohort studies on cART-naïve adults from cART initiation. We used Cox models to estimate hazard ratios for death and AIDS among IDUs and non-IDUs. The cumulative incidence of specific causes of death was calculated and compared using methods that allow for competing risks. RESULTS: Data on 6269 IDUs and 37 774 non-IDUs were analysed. Compared with non-IDUs, a lower proportion of IDUs initiated cART with a CD4 cell count <200 cells/µL or had a prior diagnosis of AIDS. Mortality rates were higher in IDUs than in non-IDUs (2.08 vs. 1.04 per 100 person-years, respectively; P<0.001). Lower baseline CD4 cell count, higher baseline HIV viral load, clinical AIDS at baseline, and later year of cART initiation were associated with disease progression in both groups. However, the inverse association of baseline CD4 cell count with AIDS and death appeared stronger in non-IDUs than in IDUs. The risk of death from each specific cause was higher in IDUs than non-IDUs, with particularly marked increases in risk for liver-related deaths, and those from violence and non-AIDS infection. CONCLUSION: While liver-related deaths and deaths from direct effects of substance abuse appear to explain much of the excess mortality in IDUs, they are at increased risk for many other causes of death, which may relate to suboptimal management of HIV disease in these individuals.

Comparative effectiveness of continuing a virologically effective first-line boosted protease inhibitor combination or of switching to a three-drug regimen containing either efavirenz, nevirapine or abacavir.

OBJECTIVES: To compare virological effectiveness in patients who continued on a virologically successful first-line boosted protease inhibitor (PI)-containing combination antiretroviral therapy (cART) regimen or who switched to a PI-free cART including efavirenz, nevirapine or abacavir. METHODS: From the French Hospital Database on HIV, we selected 439 patients with undetectable viral load (VL) on a first-line boosted PI-containing cART regimen who switched to a PI-free combination including efavirenz, nevirapine or abacavir. Each of these patients was matched with three patients who continued to take their first-line cART regimen, on the basis of gender, age, CD4 cell count, VL, date of cART initiation and the duration of VL undetectability. Time to virological failure (VF) was analysed with Kaplan-Meier curves and Cox models. RESULTS: The 12 month probabilities of VF were 3.7% and 5.7% in non-switch and switch patients, respectively, and 3.9%, 7.2% and 9.0% in patients switching to efavirenz-, nevirapine- and abacavir-containing cART, respectively. After adjustment, only patients switching to abacavir-containing cART had a higher risk of VF than non-switch patients (adjusted hazard ratio, 1.99; 95% confidence interval, 1.05-3.79). CONCLUSIONS: Switching from a virologically successful first-line boosted PI-containing cART regimen to a non-nucleoside reverse transcriptase inhibitor-containing cART regimen containing either efavirenz or nevirapine is virologically safe, while switching to abacavir-containing cART should be avoided.

[Multidrug-resistant tuberculosis management in three French hospitals]. / Prise en charge de la tuberculose multirésistante dans trois hôpitaux français.

INTRODUCTION: Multidrug-resistant tuberculosis (MDR-TB) management is based on specific WHO guidelines. OBJECTIVES: The authors report MDR-TB management, in three French hospitals. METHOD: The authors retrospectively included patients with positive sample for multidrug-resistant Mycobacterium tuberculosis (isoniazid+rifampicin) from January 1, 2000 to December 31, 2005. The management was compared to the French and international prevalent guidelines. RESULTS: Sixteen patients were initially managed for MDR-TB by eight different medical teams over 6 successive years: 12 (75%) presented with primary MDR-TB. Management advice from the national referee center (NRC) for tuberculosis was reported in seven out of 14 treated cases. The median length of the intensive treatment was 2 months (IQR: 1-3). Eight patients (58%) had an overall treatment length of 18 months. The median number of effective drugs prescribed was 4 (IQR: 4-5). Nine patients (64%) were also managed in a sanatorium. Only eight patients (57%) completed the prescribed treatment. Nine patients were clinically cured and still followed-up, six of whom were bacteriologically cured. CONCLUSION: TB-MDR management was not conform to WHO guidelines in our study. Management in a sanatorium, NRC involvement, ambulatory DOT were highly beneficial.

Does enfuvirtide increase the risk of bacterial pneumonia in patients receiving combination antiretroviral therapy?

BACKGROUND: Pooled analysis of the TORO comparative clinical trial data sets showed a significantly higher incidence rate (IR) of bacterial pneumonia (BP) among patients treated with enfuvirtide-containing combination antiretroviral therapy (ENF-cART) than in those treated with other cART regimens. OBJECTIVES: To examine the possible impact of ENF-cART on the risk of BP. METHODS: From the French Hospital Database on HIV, we selected two groups of patients among cART-treated patients who were prescribed a new cART regimen during the period 2001-2006, when their CD4 counts were <350 cells/mm(3). The ENF-cART and cART groups consisted of 1220 and 9374 patients, respectively. Poisson regression models were used to quantify the relationship between ENF-cART therapy and the risk of BP. RESULTS: At baseline the median CD4 counts were 100 and 211 cells/mm(3) and the median plasma viral load (pVL) values were 60 276 and 2702 copies/mL in the ENF-cART and cART groups, respectively. The respective BP IRs were 0.65 [95% confidence interval (CI) 0.25-1.06] and 0.31 (95% CI 0.25-0.38) cases per 100 person-years. After adjustment for age, the HIV transmission group, the time period, co-trimoxazole prophylaxis, and stratified CD4 cell counts and pVL values, we found that the BP risk ratio was not increased by enfuvirtide treatment (relative rate 1.39; 95% CI 0.46-4.13). In contrast, lower CD4 cell counts and higher pVL values were significantly associated with a higher risk of BP. CONCLUSIONS: ENF-cART is not associated with a significantly higher risk of BP than other cART regimens, although the value of the adjusted risk and the upper limit of the CI do not allow us to exclude a small increased risk.

[Metastatic extraskeletal osteosarcoma revealed by an occipital mass]. / Ostéosarcome extrasquelettique d'emblée métastatique révélé par une masse occipitale.

BACKGROUND: Extraskeletal osteosarcoma is a rare mesenchymatous tumour occurring in adults aged over 50 years and is located mainly in the limbs or retroperitoneum. We report a case of metastatic extraskeletal osteosarcoma revealed by a cutaneous occipital tumour site. CASE-REPORT: A 53-year-old woman was admitted for dyspnea and weight loss. An occipital tumour, noticed for one year by the patient, was discovered. It was freely movable on the bone, of hard consistency and responsible for alopecia. In addition to left-sided pleural effusion, a chest CAT revealed a large mass in the left lung, including areas of necrosis and calcifications with intracardiac extension. Histological examination of biopsies of the skin and of pulmonary and intracardiac lumps showed an osteosarcomatous proliferation. No primary osteosarcoma was found in the bones. A diagnosis was made of metastatic extraskeletal osteosarcoma. Intravenous chemotherapy was given followed by radiotherapy. After a six-month stabilization period, the disease progressed. DISCUSSION: Extraskeletal cutaneous locations of osteosarcoma are extremely rare. They may comprise either the primary tumour or a metastatic lesion. In this patient, the immediately metastatic nature of the disease was a poor prognostic factor for this high-grade sarcoma.

Anti-PGL-Tb1 responses as an indicator of the immune restoration syndrome in HIV-TB patients.

A prospective and multi-centre study has allowed us to analyse antibody responses and Mycobacterium tuberculosis clinical isolate genotypes on 24 consecutive HIV-TB co-infected patients treated with Highly Active Antiretroviral Therapy (HAART) who either went on to develop a TB Immune Restoration Syndrome (TB-IRS), or not. Circulating free and immune-complexed antibodies against ManLAM, ESAT-6/CFP10 and PGL-Tb1 in HIV-TB co-infected patients were measured by ELISA at the initiation of anti-TB treatment, at the date of HAART initiation and thereafter. Presence of circulating B cells was also monitored by in vitro antibody production (IVAP) against ESAT-6/CFP10 and PGL-Tb1. Finally, 16 out of 24M. tuberculosis clinical isolates from patients with TB-IRS were genotyped using spoligotyping and MIRUs-VNTR typing. Eleven patients (45.8%) experienced TB-IRS (TB-IRS+). Significantly, lower anti-PGL-Tb1 antibody levels were identified in TB-IRS+ compared to TB-IRS-negative patients prior to TB-IRS development. These very low levels were neither related to CD4 counts nor with complexed antibodies. No difference in antibody levels was observed with the other tested antigens. In addition, no specific strain genotype was associated with TB-IRS. The presence of specific anti-PGL-Tb1 antibodies only in TB-IRS-negative patients represents for the first time an indicator of a potential protective response or a diagnostic biomarker for the detection of non-progression to TB-IRS in HIV-TB co-infected patients starting HAART.

Tumors in organ transplant recipients may give clues to their control by immunity.

Tumors in solid organ transplant recipients are an important complication of surgery. They can be due to the recurrence of malignancy existing in the recipient prior to transplantation, tumors of donor origin transmitted inadvertently and de novo malignancies. These patients constitute a sort of experimental group in whom the normal immune control of the host has been weakened and can provide valuable information. The reported distribution of the tumors developed in these patients may indicate those whose development is controlled by the immune system. Some of the reported data has been unexpected. For example, patients grafted to treat a primary cancer or in whom an asymptomatic tumor was discovered at the time of transplantation rarely have a recurrence. Many of these were skin tumors, but why the SCC/BCC incidence ratio is far from 1 is unclear. Melanomas are not more frequent among immunosuppressed grafted patients, in spite of the fact that they have specific antigens which could be targets for immune and tumor growth control. Some tumors regress and disappear when the immunosuppression regimen is withdrawn. Tumor types rarely observed in grafted patients are thus immune-insensitive and would not normally regress due to immunotherapy.

Incidence and risk factors for toxoplasmic encephalitis in human immunodeficiency virus-infected patients before and during the highly active antiretroviral therapy era.

The occurrence of toxoplasmic encephalitis (TE) was studied among 19,598 and 17,016 patients enrolled in the French Hospital Database on human immunodeficiency virus whose CD4 cell counts decreased to < or =200x10(6) cells/L before (1992-1995) or after (1996-1998) the availability of highly active antiretroviral therapy, respectively. The incidence of TE decreased from 3.9 cases per 100 person-years in the first period (95% confidence interval [CI], 3.7-4.1) to 1.0 cases per 100 person-years in the second period (95% CI, 0.9-1.1). After adjustment for known risk factors for TE, patients who received cotrimoxazole prophylaxis had a lower risk of TE (adjusted relative hazard, 0.6 and 0.5, respectively, for the first and second periods; P < .001). For patients treated with cotrimoxazole at inclusion, discontinuation of cotrimoxazole increased the risk of TE in both periods (adjusted relative hazard, 4.8 and 4.2, respectively; P < .001). Among patients whose CD4 cell counts increased to > 200 x 10(6) cells/L while undergoing highly active antiretroviral therapy, the incidence of TE was 0.1 cases per 100 person-years (95% CI, 0.0-0.2) and was not increased by discontinuation of cotrimoxazole.

Risk factors for esophageal candidiasis in a large cohort of HIV-infected patients treated with nucleoside analogues.

To assess the risk factors for esophageal candidiasis (EC), a cohort study and a case-control study were conducted using 1,368 French patients who were already participating in the Delta trial (which compared different types of antiretroviral therapy in HIV-infected patients) and who had no previous history of EC. During a median follow-up period of 19 months, 87 (6%) patients developed EC. The results of the cohort study showed an increased risk of EC associated with a low baseline CD4+ cell count (P<0.0001), a high baseline plasma HIV RNA level (P < 0.0001) and prior zidovudine therapy (P = 0.02) at entry to the study. The case-control study revealed an increased risk of EC in patients with a recent low CD4+ cell count (P < 0.0002), recent antibacterial chemotherapy (P = 0.01) and oral candidiasis (P < 0.05). Cotrimoxazole prophylaxis also increased the risk of EC (P = 0.04) in the case-control study.