Increased risk of severe COVID-19 in hospitalized patients with SARS-CoV-2 Alpha variant infection: a multicentre matched cohort study.

BACKGROUND: The impact of the variant of concern (VOC) Alpha on the severity of COVID-19 has been debated. We report our analysis in France. METHODS: We conducted an exposed/unexposed cohort study with retrospective data collection, comparing patients infected by VOC Alpha to contemporaneous patients infected by historical lineages. Participants were matched on age (± 2.5 years), sex and region of hospitalization. The primary endpoint was the proportion of hospitalized participants with severe COVID-19, defined as a WHO-scale > 5 or by the need of a non-rebreather mask, occurring up to day 29 after admission. We used a logistic regression model stratified on each matched pair and accounting for factors known to be associated with the severity of the disease. RESULTS: We included 650 pairs of patients hospitalized between Jan 1, 2021, and Feb 28, 2021, in 47 hospitals. Median age was 70 years and 61.3% of participants were male. The proportion of participants with comorbidities was high in both groups (85.0% vs 90%, p = 0.004). Infection by VOC Alpha was associated with a higher odds of severe COVID-19 (41.7% vs 38.5%-aOR = 1.33 95% CI [1.03-1.72]). CONCLUSION: Infection by the VOC Alpha was associated with a higher odds of severe COVID-19.

Is Rifampin Use Associated With Better Outcome in Staphylococcal Prosthetic Valve Endocarditis? A Multicenter Retrospective Study.

BACKGROUND: International guidelines recommend rifampin-based combinations for staphylococcal prosthetic valve endocarditis (PVE). However, no robust clinical data support this recommendation, and rifampin tolerability is an issue. We aimed to evaluate the impact of rifampin for the treatment of staphylococcal PVE. METHODS: An observational retrospective cohort study of all adults with staphylococcal PVE (modified Duke criteria) was conducted in 3 referral centers for endocarditis, during years 2000-2018. Primary outcome measurement was 1-year mortality. RESULTS: We enrolled 180 patients with PVE due to Staphylococcus aureus (n = 114, 63.3%), or coagulase-negative staphylococci (n = 66, 36.7%), on bioprosthesis (n = 111, 61.7%), mechanical valve (n = 67, 37.2%), or both (n = 2). There were 132 males (73.3%), and mean age was 70.4 ± 12.4 years. Valvular surgery was performed in 51/180 (28.3%) cases. Despite all isolates were susceptible to rifampin, only 101 (56.1%) were treated with rifampin, for a median duration of 33.0 days, whereas 79 (43.9%) received no rifampin. Baseline characteristics were similar in both groups. One-year mortality was, respectively, 37.6% (38/101), and 31.6% (25/79), in patients treated with, or without, rifampin (P = .62). Relapse rates were 5.9% (6/101), and 8.9% (7/79), P = .65. Patients treated with rifampin had longer hospital length-of-stay: 42.3 ± 18.6 vs 31.3 ± 14.0 days (P < .0001). On multivariate analysis, only cerebral emboli (odds ratio [OR] 2.95, 95% confidence interval [CI], 1.30-6.70, P = .009), definite endocarditis (OR 7.15, 95% CI, 1.47-34.77, P = .018), and methicillin-resistant S. aureus (OR 6.04, 95% CI, 1.34-27.26, P = .019), were associated with 1-year mortality. CONCLUSIONS: A large proportion (43.9%) of staphylococcal PVE received no rifampin. One-year survival and relapse rates were similar in patients treated with or without rifampin.

Likely effect of the 2014 Ebola epidemic on HIV care in Liberia.

OBJECTIVE: Liberia's health system has been severely struck by the 2014 Ebola epidemic. We aimed to assess the potential effect of this epidemic on the care of HIV patient in two clinics [John F. Kennedy (JFK) and Redemption Hospitals] in Monrovia, which stayed open throughout the epidemic. DESIGN AND METHODS: A preexisting electronic database of HIV patient's follow-up visits was used to estimate three weekly parameters from January 2012 to October 2014: number of visits, number of new patient, and proportion of patients with follow-up delay. We used segmented negative binomial regressions to assess trends before and after the week of the Ebola outbreak defined in June 2014 by WHO. RESULTS: The cumulative number of patients in care comprised 5948 patients with a total of 56 287 visits between January 2012 and October 2014. From June 2014, the number of visit per week, stable since 2012, abruptly decreased (59%) in Redemption (P < 0.001) and progressively decreased by 3% per week in JFK (P < 0.001). In both the clinics, the weekly proportion of patient with follow-up delay sharply increased after the point break from June 2014 (P value < 0.001). From June 2014, a significant decrease in new patients per week occurred in both the clinics: by 57% (P value < 0.001) in Redemption and by 4.6% per week (P value < 0.001) in JFK. CONCLUSION: The Ebola epidemic had a significant effect on HIV care in Monrovia. Given the particular impact on the rate of patients with follow-up delay, a long-term impact is feared.

Prevalence of HIV-1 drug resistance among patients failing first-line ART in Monrovia, Liberia: a cross-sectional study.

OBJECTIVES: To assess the prevalence of acquired drug resistance in HIV-1-infected patients living in Monrovia, Liberia, who had clinical and/or immunological failure of first-line ART according to WHO criteria. PATIENTS AND METHODS: Patients receiving ART for >1 year with clinical and/or immunological failure were included. Sequencing of protease and reverse transcriptase regions was performed using Agence Nationale de Recherche sur le SIDA et les hépatites virales (ANRS) procedures and sequences were interpreted using the ANRS resistance algorithm. RESULTS: Ninety patients were enrolled. They had been receiving ART for a median time of 42 months and half were receiving zidovudine/lamivudine/nevirapine. Seventy-five per cent of patients were infected with CRF02_AG. Twenty-seven per cent of patients displayed a plasma viral load <50 copies/mL. Among the 66 patients with detectable viraemia, the median viral load was 4.7 log10 copies/mL (IQR = 3.0-5.6). The prevalence of NRTI and NNRTI resistance-associated mutations (RAMs) was 63% and 71%, respectively; and the median number of NRTI and NNRTI RAMs was 2 and 3, respectively. Two patients (4%) displayed viruses with PI RAMs. Regarding NRTI drug resistance, 29%, 38%, 63%, 29% and 25% of patients had viruses resistant to zidovudine, stavudine, lamivudine/emtricitabine, abacavir and tenofovir, respectively. Regarding the NNRTI drug class, 56%, 65%, 33% and 42% of patients had viruses resistant to efavirenz, nevirapine, etravirine and rilpivirine, respectively. CONCLUSIONS: The high prevalence of acquired drug resistance in patients followed in two centres of the Liberian capital city, documented after a median of 3 years on a first-line ART regimen, jeopardizes the activity of second-line regimens and highlights the need for virological monitoring in these settings.

Prevalence of and risk factors for acute mountain sickness among a cohort of high-altitude travellers who received pre-travel counselling.

BACKGROUND: Acute mountain sickness (AMS) is common in high-altitude travellers, and may lead to life-threatening high-altitude cerebral oedema. To better target pre-travel counselling, we aimed to characterize the risk factors for AMS that may be identified prior to departure. METHODS: We performed a descriptive study of high-altitude travellers who consulted at a travel clinic before departure. Data were collected by phone after their return, using a standardized questionnaire. RESULTS: 162 adults were enrolled. Most subjects (81.5%) were informed about AMS before departure, by a medical doctor in 40% of cases. AMS symptoms were reported by 77 travellers (47.5%). Variables significantly associated with AMS symptoms were female sex (56% versus 38.5%, p = 0.01), trip organised by a travel agency (55.2% versus 43.3%, p = 0.03), travel duration (mean, 4.2 ± 3.5 weeks in patients with AMS, versus 6.6 ± 7.5 weeks in patients without AMS, p = 0.014), and acetazolamide use (71.4% versus 47.5%, p = 0.045). In multivariate analysis, only female sex was independently predictive of AMS (adjusted OR 2.15 [1.14-4.40]). CONCLUSIONS: AMS symptoms occur in almost half of high-altitude travellers. Women, and travellers leaving for short duration, within trips organised by travel agencies, should be targeted for enhanced pre-travel counselling to prevent AMS.

Short communication: Prevalence of HIV-1 transmitted drug resistance in Liberia.

No data on HIV-transmitted drug resistance (TDR) are available in Liberia in which the HIV prevalence in the general population is estimated at 1.5%. The aim of the study was to assess the prevalence of TDR in HIV-1 from recently diagnosed and untreated patients living in Monrovia, Liberia. The study was performed in the John F. Kennedy Medical Center and in the Redemption Hospital, both located in Monrovia. All newly HIV-1 diagnosed patients attending voluntary counseling testing centers and antiretroviral therapy naive were consecutively included. Protease and reverse transcriptase (RT) regions sequencing was performed using the ANRS procedures (www.hivfrenchresistance.org). Drug resistance mutations (DRM) were identified according to the 2009 updated WHO surveillance DRM list. Among the 116 HIV-1-infected patients enrolled in the study, 85 (73%) were women. Protease and RT sequencing was successful in 109 (94%) and 102 (88%) samples, respectively. Seventy-five (66%) patients were infected with CRF02_AG. One DRM was observed in six samples, leading to a TDR prevalence of 5.9% (CI 95%=1.7-10.1). DRM were observed in two patients (2.0%; CI 95%=0.0-4.7), four patients (3.9%; CI 95%=0.1-7.7), and one patient (0.9%; CI 95%=0.0-2.7) for nucleoside RT inhibitors (NRTI), non-NRTI (NNRTI), and protease inhibitors, respectively. Overall, one patient exhibited dual class-resistant viruses, harboring NRTI and NNRTI resistance mutations (1.0%; CI 95%=0.0-2.9). This first survey study in Liberia reported a TDR prevalence of 5.9%, classified as moderate according to the WHO criteria, indicating that further surveillance is warranted to follow the level and evolution of TDR prevalence in recently HIV-1 diagnosed patients.

Short-term decline in all-cause acquired infections with the routine use of a decontamination regimen combining topical polymyxin, tobramycin, and amphotericin B with mupirocin and chlorhexidine in the ICU: a single-center experience.

OBJECTIVES: In a multicenter, placebo-controlled, randomized, double-blind trial, we showed that acquired infections in intubated patients were reduced by the combination of topical polymyxin plus tobramycin and nasal mupirocin plus chlorhexidine body wash. Because intubated patients are particularly at risk for acquired infections, we reassessed the impact of this protocol as a routine procedure to control acquired infections in the ICU. DESIGN: Nonrandomized study comparing acquired infections in ICU patients during two 1-year periods: the last year before (group A, n = 925) and the first year after the implementation of the protocol (group B, n = 1,022). Acquired infections were prospectively recorded. SETTING: Polyvalent medical ICU at a university-affiliated hospital. PATIENTS: All patients admitted to the ICU. INTERVENTIONS: Administration of polymyxin/tobramycin/amphotericin B in the oropharynx and the gastric tube plus a mupirocin/chlorhexidine regimen in intubated patients and standard care in the other patients. MEASUREMENTS AND MAIN RESULTS: The comparison of acquired infection rates between groups was adjusted for differences at baseline. Infection rates were lower in group B compared with group A (5.3% vs 11.0%; p < 0.001), as were the incidence rates of total acquired infections (9.4 vs 23.6 per 1,000 patient-days; p < 0.001), intubation-related pneumonia (5.1 vs 17.1 per 1,000 ventilator-days; p < 0.001), and catheter-related bloodstream infections (1.0 vs 3.5 per 1,000 catheter-days; p = 0.03). There were fewer acquired infections caused by ceftazidime-resistant Enterobacteriaceae (0.8‰ vs 3.6‰; p < 0.001), ciprofloxacin-resistant Enterobacteriaceae (0.8‰ vs 2.5‰; p = 0.02), ciprofloxacin-resistant Pseudomonas aeruginosa (0.5‰ vs 1.6‰; p = 0.05), and colistin-resistant Gram-negative bacilli (0.7‰ vs 1.9‰; p = 0.04). Fewer patients got acquired infections due to multidrug-resistant aerobic Gram-negative bacilli (p = 0.008). CONCLUSIONS: In intubated patients, the use of topical polymyxin/tobramycin/amphotericin B plus mupirocin/chlorhexidine was associated with the reduction of all-cause ICU-acquired infections. Long-term emergence of multidrug-resistant organisms deserves further investigation.

Full-text automated detection of surgical site infections secondary to neurosurgery in Rennes, France.

The surveillance of Surgical Site Infections (SSI) contributes to the management of risk in French hospitals. Manual identification of infections is costly, time-consuming and limits the promotion of preventive procedures by the dedicated teams. The introduction of alternative methods using automated detection strategies is promising to improve this surveillance. The present study describes an automated detection strategy for SSI in neurosurgery, based on textual analysis of medical reports stored in a clinical data warehouse. The method consists firstly, of enrichment and concept extraction from full-text reports using NOMINDEX, and secondly, text similarity measurement using a vector space model. The text detection was compared to the conventional strategy based on self-declaration and to the automated detection using the diagnosis-related group database. The text-mining approach showed the best detection accuracy, with recall and precision equal to 92% and 40% respectively, and confirmed the interest of reusing full-text medical reports to perform automated detection of SSI.

The effects of a maintenance therapy with peg-interferon alpha-2a on liver fibrosis in HIV/HCV co-infected patients: a randomized controlled trial.

OBJECTIVE: We hypothesized that, in Human Immunodeficiency Virus and Hepatitis C Virus (HIV/HCV) co-infected patients who did not respond to peg-interferon and ribavirin, a maintenance therapy with peg-interferon could induce fibrosis regression. METHODS: This was a randomized study with two parallel groups. HIV/HCV co-infected patients received peg-interferon α-2a at 180 µg/week or remained on observation for 96 weeks. The primary endpoint was the percentage of patients who experienced a decrease of at least one point in their Metavir fibrosis score between initial and final liver biopsies. Secondary endpoints included plasma fibrosis markers at week 96, occurrence of HCV-related complications, and survival. RESULTS: A total of 52 patients were randomized (peg-interferon: 25; control: 27) including 18 with cirrhosis. The median (interquartile range) age was 44 (40-46) years, and 69% were male. A total of 64% had ALT levels >1.5 normal values, and the CD4 cell count was 391 (296-537) cells/mm(3); 67% of patients had HIV RNA <200 copies/mL at entry. The main endpoint was assessed in 41 patients. Response rates were 3/20 (15%) and 4/21 (19%) in the peg-interferon and control groups, respectively (p = 0.99). There was no significant difference between peg-interferon and control groups on plasma fibrosis markers at the final visit. Severe liver-related complications were observed in 2 and 5 patients in peg-interferon and control groups, respectively. Three deaths were observed, all in the control group. CONCLUSIONS: A maintenance therapy with peg-interferon α-2a over 96 weeks in HIV/HCV co-infected patients, who were non-responders to HCV treatment, did not change liver fibrosis. ClinicalTrials.gov Identifier: NCT00122616.

Mitochondrial abnormalities in patients with HIV-HCV co-infection as compared to patients with HCV mono-infection.

INTRODUCTION: Mitochondrial dysfunction is a classic complication of HIV infection and its treatment and has also been reported in hepatitis C virus (HCV)-infected patients. Little is known about interactions between both viruses on mitochondrial metabolism. METHODS: We performed a cross-sectional study of HCV-infected patients who underwent liver biopsy as part of their routine care. Mitochondrial function was assessed by (a) liver morphological (histology) and functional (spectro-photometry) studies, and (b) serum lactate kinetics, oxygen uptake, and anaerobic threshold measurement during standardized incremental exercise. Three predefined groups of patients were compared. RESULTS: Thirty-eight HCV-infected patients were included: 13 not HIV infected (group 1), 7 with HIV co-infection and low nucleoside reverse transcriptase inhibitor (NRTI) exposure (none over the last 2 years; group 2), and 18 with HIV co-infection and high NRTI exposure (group 3). On liver biopsies, respiratory chain complex IV activity was impaired, at 5 (2-7) nmol/min/mg substrates in group 1, 5 (3-8) in group 2, and 8 (2-13) in group 3 (normal values, 20-56). Maximal power output was diminished and anaerobic threshold occurred earlier in HIV-infected patients, regardless of NRTI exposure. CONCLUSION: HCV has deleterious effects on liver mitochondrial metabolism, notably on respiratory chain complex IV. No significant interaction with HIV was observed.

The use of drug resistance algorithms and genotypic inhibitory quotient in prediction of lopinavir-ritonavir treatment response in human immunodeficiency virus type 1 protease inhibitor-experienced patients.

BACKGROUND: Different approaches using genotypic, pharmacokinetic parameters or combination of both have been recently developed to monitor antiretroviral treatment in HIV-1-infected individuals. Their uses in clinical practice may improve the benefit of protease inhibitor-based salvage therapy while reducing treatment toxicity and emergence of viral resistance. OBJECTIVES: To assess the prediction of genotypic inhibitory quotient (GIQ) using different genotypic drug resistance interpretation's algorithms and lopinavir plasma concentration in PI-experienced patients treated by lopinavir/ritonavir (LPV/r). Genotypic susceptibility score (GSS) was also evaluated. STUDY DESIGN: Forty-seven HIV-1 PI-experienced, but LPV naïve patients were included in a retrospective cohort study. Plasma HIV-1 viral load (VL), CD4 cell count and LPV plasma concentrations were assessed at weeks (W) 12 and 24. Interpretation of baseline resistance genotype was achieved according to four different algorithms and GSS calculated using two expert systems. GIQ was defined as the ratio of LPV concentration to the number of LPV resistance mutations at day 0 (D0) and patients classified by units of GIQ. The end point of the study was the virological response expressed in HIV VL median decrease from D0 to W24. RESULTS: The overall median VL decrease from D0 to W24 was -2.42 log(10)copies/mL and 60% of patients had VL below 400 copies/mL. The LPV mutation score was predictive of response for all algorithms whereas plasma concentrations of LPV were not. Mean VL decrease was greater for higher GIQ classes and difference reached statistical significance at W24. When considering virological response at W24, GSS calculated with ANRS and Stanford system were good predictor scores as areas under the receiver operating characteristics (ROC) curves were 0.76 for both. CONCLUSION: GIQ was found to be a useful drug-monitoring tool which could be helpful in targeting LPV concentrations in order to achieve long-term undetectable viral load, particularly in genotypic resistant patients.

Increasing incidence of severe Epstein-Barr virus-related infectious mononucleosis: surveillance study.

Older patients are more susceptible to severe Epstein-Barr virus (EBV)-related infectious mononucleosis (IM). This condition may increase in industrialized countries where primary EBV infection occurs later in life. Between 1990 and 2004, 38 patients were admitted to our department with EBV-related IM. Two patients died. The annual incidence increased significantly (r = 0.623; P = 0.013).

Mitochondrial abnormalities in HIV-infected lipoatrophic patients treated with antiretroviral agents.

BACKGROUND: Lipodystrophy is now widely described in HIV infected patients under antiretroviral regimen with important psychological impact. But physiopathology of loss of fat mass is still debated and the role of mitochondrial impairment is not clearly defined. OBJECTIVE: To correlate clinical lipoatrophy (LA) in HIV patients with long-term treatment by nucleoside reverse transcriptase inhibitors (NRTIs) and muscular impairment related to mitochondrial dysfunction. METHODS: Ten consecutive patients with clinical LA and 10 nonlipodystrophic (NLD) individuals on antiretroviral therapy were included. Patients underwent the following investigations: dual-energy x-ray absorptiometry (DEXA) scanning and lactate kinetics during standardized exercise. The mitochondrial respiratory complex activity (III and IV) and histoenzymatic abnormalities (classified as none, mild, or severe) were evaluated on muscle tissue obtained by biopsy in deltoid muscle. RESULTS: Mean NRTI exposure was longer in the LA group than in the NLD group (81 +/- 30 months vs. 59 +/- 15 months), but mean protease inhibitor exposure was identical in both groups. Mean fat mass distribution for leg in the LA and NLD groups was 860 +/- 381 g versus 1895 +/- 999 g, respectively. The lactic acidosis threshold during exercise was reached in the LA group at lower workloads (mean: 45 +/- 17 W in the LA group vs. 68 +/- 11 W in the NLD group), and maximum power output exercise was restricted in LA patients (mean: 115 +/- 30 W vs. 153 +/- 28 W). Total complex activities in muscular tissue were lower in LA patients: the median (range) for complex III was 67 (1-128) versus 112 (28-143), and the median (range) for complex IV was 28 (1-70) versus 42 (1-75). Six patients had severe histoenzymatic abnormalities in the LA group versus none in the NLD group. CONCLUSION: Clinical LA, confirmed by DEXA, in long-term NRTI-treated patients was associated with muscular mitochondrial dysfunction as shown by rapid lactic acidemia increase, impairment of respiratory chain activity for complexes III and IV, and mitochondrial histoenzymatic abnormalities.

Simultaneous quantitative assay of six HIV protease inhibitors, one metabolite, and two non-nucleoside reverse transcriptase inhibitors in human plasma by isocratic reversed-phase liquid chromatography.

A rapid (less than 30 min), sensitive, and specific liquid chromatography method for simultaneous assay of nine antiretroviral drugs in human plasma is described. This technique allows therapeutic drug monitoring of six approved protease inhibitors (amprenavir, indinavir, lopinavir, nelfinavir, ritonavir, and saquinavir) and two approved non-nucleoside reverse transcriptase inhibitors (efavirenz and nevirapine). Assays were performed after diethyl ether liquid-liquid extraction from 250-microL plasma samples. Chromatographic separation was achieved on an X-TERRA (Waters; Saint Quentin, France) column using a 58% water (with 3 mmol/L pyrrolidine) and 42% acetonitrile mobile phase. Three ultraviolet wavelengths were used for detection with a diode array detector. This method allowed quantitative assay of all nine antiretroviral drugs within a concentration range of 25 ng/mL to 9000 ng/mL. The method has been validated extensively and has been in routine use in our laboratory for several months for drug monitoring in plasma samples from patients treated with antiretroviral drugs.

Salvage therapy with amprenavir and ritonavir: prospective study in 17 heavily pretreated patients.

OBJECTIVE: To evaluate the safety profile and efficacy of salvage regimens containing amprenavir (APV) 600 mg twice daily and ritonavir (RTV) 200 mg twice daily. DESIGN: Prospective, single-center study. METHOD: The patient database of the department of infectious diseases was screened for patients who had failed at least two successive three-drug combinations. These patients were proposed to take APV and RTV in association with two to four other drugs. They were followed monthly for 6 months. RESULTS: Seventeen patients were included. They had been previously treated for 70 +/- 23 months. At baseline, viral load (VL) was 4.86 +/- 0.98 log10 copies/mL and CD4 187 +/- 145 10(6)/L. On week 24, using intent-to-treat analysis, VL decreased to 2.95 +/- 1.59 log10 copies/mL and CD4 increased to 365 +/- 210 10(6)/L. Nine patients (53%) had a VL < 2.3 log10 copies/mL. The most common adverse events were grade 1 or 2 diarrhea and an increase of cholesterol and triglyceride levels. Mean APV trough concentration was 1727 +/- 1749 ng/mL on week 24. CONCLUSION: These data show that the combination of low-dose RTV and reduced doses of APV is safe. This combination can be added to nonnucleoside analogs.