Spreading of SARS-CoV-2 in West Africa and assessment of risk factors.

Although the African continent is, for the moment, less impacted than the rest of the world, it still faces the risk of a spread of COVID-19. In this study, we have conducted a systematic review of the information available in the literature in order to provide an overview of the epidemiological and clinical features of COVID-19 pandemic in West Africa and of the impact of risk factors such as comorbidities, climatic conditions and demography on the pandemic. Burkina Faso is used as a case study to better describe the situation in West Africa. The epidemiological situation of COVID-19 in West Africa is marked by a continuous increase in the numbers of confirmed cases. This geographic area had on 29 July 2020, 131 049 confirmed cases by polymerase chain reaction, 88 305 recoveries and 2102 deaths. Several factors may influence the SARS-CoV-2 circulation in Africa: (i) comorbidities: diabetes mellitus and high blood pressure could lead to an increase in the number of severe cases of SARS-CoV-2; (ii) climatic factors: the high temperatures could be a factor contributing to slow the spread of the virus and (iii) demography: the West Africa population is very young and this could be a factor limiting the occurrence of severe forms of SARS-CoV-2 infection. Although the spread of the SARS-CoV-2 epidemic in West Africa is relatively slow compared to European countries, vigilance must remain. Difficulties in access to diagnostic tests, lack of hospital equipment, but also the large number of people working in the informal sector (such as trading, businesses, transport and restoration) makes it difficult to apply preventive measures, namely physical distancing and containment.

Usutu virus: A new threat?

Usutu virus (USUV) is an emerging arbovirus that was first isolated in South Africa in 1959. This Flavivirus is maintained in the environment through a typical enzootic cycle involving mosquitoes and birds. USUV has spread to a large part of the European continent over the two decades mainly leading to substantial avian mortalities with a significant recrudescence of bird infections recorded throughout Europe within the few last years. USUV infection in humans is considered to be most often asymptomatic or to cause mild clinical signs. Nonetheless, a few cases of neurological complications such as encephalitis or meningoencephalitis have been reported. USUV and West Nile virus (WNV) share many features, like a close phylogenetic relatedness and a similar ecology, with co-circulation frequently observed in nature. However, USUV has been much less studied and in-depth comparisons of the biology of these viruses are yet rare. In this review, we discuss the main body of knowledge regarding USUV and compare it with the literature on WNV, addressing in particular virological and clinical aspects, and pointing data gaps.

Efficacy, safety and patient-reported outcomes of ledipasvir/sofosbuvir in NS3/4A protease inhibitor-experienced individuals with hepatitis C virus genotype 1 and HIV coinfection with and without cirrhosis (ANRS HC31 SOFTRIH study).

OBJECTIVES: Studies evaluating the efficacy and safety of the fixed-dose combination ledipasvir (LDV)/sofosbuvir (SOF) in patients coinfected with HIV-1 and hepatitis C virus (HCV) have mainly included treatment-naïve patients without cirrhosis. We aimed to evaluate the efficacy and safety of this combination in treatment-experienced patients with and without cirrhosis. METHODS: We conducted a multicentre, open-label, double-arm, nonrandomized study in patients coinfected with HIV-1 and HCV genotype 1 with and without cirrhosis, who had good viral suppression on their antiretroviral regimens. All patients were pretreated with a first-generation NS3/4A protease inhibitor (PI) plus pegylated interferon/ribavirin. Patients received a fixed-dose combination of LDV/SOF for 12 weeks, or for 24 weeks if cirrhosis was present. The primary endpoint was a sustained virological response (SVR) 12 weeks after the end of therapy. Secondary endpoints included safety, pharmacokinetics and patient-reported outcomes. RESULTS: Of the 68 patients enrolled, 39.7% had cirrhosis. Sixty-five patients [95.6%; 95% confidence interval (CI): 87.6-99.1%; P < 0.0001] achieved an SVR, with similar rates of SVR in those with and without cirrhosis. Tolerance was satisfactory, with mainly grade 1 or 2 adverse events. Among patient-reported outcomes, only fatigue significantly decreased at the end of treatment compared with baseline [odds ratio (OR): 0.36; 95% CI: 0.14-0.96; P = 0.04]. Mean tenofovir area under the plasma concentration-time curve (AUC) at week 4 was high, with mean ± SD AUC variation between baseline and week 4 higher in cirrhotic than in noncirrhotic patients (3261.57 ± 1920.47 ng/mL vs. 1576.15 ± 911.97 ng/mL, respectively; P = 0.03). Mild proteinuria (54.4%), hypophosphataemia (50.0%), blood bicarbonate decrease (29.4%) and hypokalaemia (13.2%) were reported. The serum creatinine level was not modified. CONCLUSIONS: LDV/SOF provided a high SVR rate in PI-experienced subjects coinfected with HCV genotype 1 and HIV-1, including patients with cirrhosis.

Developmental determinants in non-communicable chronic diseases and ageing.

Prenatal and peri-natal events play a fundamental role in health, development of diseases and ageing (Developmental Origins of Health and Disease (DOHaD)). Research on the determinants of active and healthy ageing is a priority to: (i) inform strategies for reducing societal and individual costs of an ageing population and (ii) develop effective novel prevention strategies. It is important to compare the trajectories of respiratory diseases with those of other chronic diseases.

Automated versus manual sample inoculations in routine clinical microbiology: a performance evaluation of the fully automated InoqulA instrument.

The process of plate streaking has been automated to improve the culture readings, isolation quality, and workflow of microbiology laboratories. However, instruments have not been well evaluated under routine conditions. We aimed to evaluate the performance of the fully automated InoqulA instrument (BD Kiestra B.V., The Netherlands) in the automated seeding of liquid specimens and samples collected using swabs with transport medium. We compared manual and automated methods according to the (i) within-run reproducibility using Escherichia coli-calibrated suspensions, (ii) intersample contamination using a series of alternating sterile broths and broths with >10(5) CFU/ml of either E. coli or Proteus mirabilis, (iii) isolation quality with standardized mixed bacterial suspensions of diverse complexity and a 4-category standardized scale (very poor, poor, fair to good, or excellent), and (iv) agreement of the results obtained from 244 clinical specimens. By involving 15 technicians in the latter part of the comparative study, we estimated the variability in the culture quality at the level of the laboratory team. The instrument produced satisfactory reproducibility with no sample cross-contamination, and it performed better than the manual method, with more colony types recovered and isolated (up to 11% and 17%, respectively). Finally, we showed that the instrument did not shorten the seeding time over short periods of work compared to that for the manual method. Altogether, the instrument improved the quality and standardization of the isolation, thereby contributing to a better overall workflow, shortened the time to results, and provided more accurate results for polymicrobial specimens.

[Determinants of low birth weight among newborns to HIV-infected mothers not eligible for antiretroviral treatment in Africa]. / Déterminants du faible poids de naissance chez des enfants nés de mères séropositives pour le VIH, non éligibles au traitement antirétroviral, en Afrique.

BACKGROUND: Low birth weight (LBW) increases the risk of infant death, but little is known about its rate and determinants among babies born to HIV-infected mothers in sub-Saharan Africa. METHODS: This study was conducted in South Africa, Burkina Faso, Uganda and Zambia, during the recruitment process of the PROMISE-PEP (ANRS 12174) clinical trial. The study sample included 1196 subjects screened between August 2009 and December 2011, respectively 254 in South Africa, 221 in Burkina Faso, 197 in Uganda and 524 in Zambia, all ineligible for antiretroviral therapy. Data were collected during ANRS12174 clinical trial antenatal and postnatal screening visits, and during an inclusion visit for completion of an electronic case report form (eCRF). RESULTS: The mean (±SD) age of mothers was 27±5years and their mean CD4 count was 576±195cells/µL. Most mothers lived in a couple (78.7%), had no employment (72.3%) and had a good level of education (74% had gone to school). Male newborns predominated (51.7%). The mean birth weight was 3043g±435g, and 7.8% ([95%CI: 6.3%-9.3%]) of newborns weighed less than 2500g. In univariate analyses, being married or cohabiting, body mass index, WHO HIV disease stage II, female newborn and low gestational age were associated with risk of LBW. In multivariate regression model, low gestational age (aOR=3.74, P<0.0001) and female newborn (aOR=1.63, P=0.04) were significantly associated with LBW. CONCLUSION: The risk factors for LBW found in HIV-infected women ineligible for antiretroviral therapy were the same as in the general population. There was no evidence of additional risk factors associated with HIV infection.

Long-term hepatitis B virus surface antigen decay in HIV-1/hepatitis B virus-coinfected adults initiating a tenofovir-containing regimen.

Hepatitis B virus (HBV) surface antigen (HBsAg) decay was explored in HIV-1- and HBV-coinfected patients beginning antiretroviral (ARV) therapy containing tenofovir disoproxil fumarate (TDF). The mean HBsAg decay was 0.38 log(10) IU/ml/year (95% confidence interval [CI], 0.71 to 0.05) in 18 patients with sustained plasma HIV-1 RNA suppression and 0.15 log(10) IU/ml/year (0.21 to 0.09) in 12 patients experiencing HIV-1 virologic failure due to suboptimal adherence to ARV (P = 0.17). We estimated that six of these 18 patients will attain HBsAg values below 10 IU/ml after 10 years of treatment.

Intrafamilial cluster of pulmonary tuberculosis due to Mycobacterium bovis of the African 1 clonal complex.

A new clonal complex of Mycobacterium bovis present at high frequency in cattle from west central African countries has been described as the African 1 (Af1) clonal complex. Here, the first intrafamilial cluster of human tuberculosis cases due to M. bovis Af1 clonal complex strains is reported. We discuss hypotheses regarding modes of transmission.

HIV-infected patients aged above 75years.

BACKGROUND: Little data is available on HIV-infected patients aged over 75years. METHODS: A descriptive study of HIV-infected patients aged over 75years was conducted in six hospitals of the Pays de la Loire region, France. Socio-demographic, immuno-virological, and therapeutic characteristics were collected via an electronic medical record software (Nadis®). To assess frailty, a simplified geriatric assessment was conducted during an HIV routine visit. RESULTS: Among the 3965 patients followed in the six centers, 65 (1.6%) were aged over 75years. From January to May 2016, 51 patients were included in the study: median age 78.7years, male patients 74.5%, homosexual transmission 41.2%, living at home 98% and single in 54.5% of cases, median duration of HIV infection 18.8years, median CD4 nadir 181 cells/mm3; CDC stage C 36.4%. All patients were on antiretroviral therapy and 98% of them had an HIV RNA<50c/mL; 82% of patients had at least one comorbidity and 58% at least two comorbidities. Eleven of 51 patients (21.6%) were diagnosed as at risk of frailty and 2/51 (3.9%) were considered frail. Cognitive disorders were diagnosed in 60.8%, depression in 35.3%, malnutrition in 25.5%, and vitamin D deficiency in 45.9%. CONCLUSIONS: HIV-infected patients aged above 75years are well-managed, but the prevalence of geriatric comorbidities is high.

Detection of SARS-CoV-2 antibodies using commercial assays and seroconversion patterns in hospitalized patients.

OBJECTIVES: SARS-CoV-2 antibody assays are needed for serological surveys and as a complement to molecular tests to confirm COVID-19. However, the kinetics of the humoral response against SARS-CoV-2 remains poorly described and relies on the performance of the different serological tests. METHODS: In this study, we evaluated the performance of six CE-marked point-of-care tests (POC) and three ELISA assays for the diagnosis of COVID-19 by exploring seroconversions in hospitalized patients who tested positive for SARS-CoV-2 RNA. RESULTS: Both the ELISA and POC tests were able to detect SARS-CoV-2 antibodies in at least half of the samples collected seven days or more after the onset of symptoms. After 15 days, the rate of detection rose to over 80% but without reaching 100%, irrespective of the test used. More than 90% of the samples collected after 15 days tested positive using the iSIA and Accu-Tell® POC tests and the ID.Vet IgG ELISA assay. Seroconversion was observed 5 to 12 days after the onset of symptoms. Three assays suffer from a specificity below 90% (EUROIMMUN IgG and IgA, UNscience, Zhuhai Livzon). CONCLUSIONS: The second week of COVID-19 seems to be the best period for assessing the sensitivity of commercial serological assays. To achieve an early diagnosis of COVID-19 based on antibody detection, a dual challenge must be met: the immunodiagnostic window period must be shortened and an optimal specificity must be conserved.

Influence of darunavir coadministration on nevirapine pharmacokinetics in HIV-infected patients: a population approach.

OBJECTIVE: The influence of ritonavir-boosted darunavir coadministration on nevirapine pharmacokinetics was investigated in HIV-infected patients using a population-based approach. METHODS: The population was composed of 51 patients (89 samples; 42 patients treated with an antiretroviral regimen containing nevirapine and nucleoside/nucleotide reverse transcriptase inhibitors and nine patients treated with a regimen containing a combination of nevirapine and darunavir). A one-compartment model with first-order absorption was fitted to the data using nonmem version V (GloboMax, Ellicott City, MD, USA). RESULTS: Relationships were established between nevirapine clearance (Cl) and age (Cl/F=2.42+47.2/age, where F denotes bioavailability) and between nevirapine volume of distribution (V(d)) and the presence of darunavir in the antiretroviral regimen [V(d)/F=38.0+75.0 (1 - darunavir coadministration), where darunavir coadministration is 1 for patients treated with a combination of nevirapine and darunavir and 0 for other patients]. According to this final model, a significant decrease in the means of Cl/F (3.84 +/- 0.92 vs. 2.76 +/- 1.00 L/h; P<0.05) and V(d)/F (93.2 +/- 31.10 vs. 39.8 +/- 6.97 L; P<0.0001) and an increase in the mean of nevirapine trough plasma concentrations (3.68 +/- 1.69 vs. 5.35 +/- 3.20 mg/L; P<0.05) are observed if nevirapine is used in combination with darunavir. CONCLUSIONS: These results suggest that nevirapine exposure is increased when nevirapine is administered in combination with darunavir and that therapeutic drug monitoring of nevirapine should be performed if this antiretroviral regimen is considered.

Detection of Mycobacterium tuberculosis in paucibacillary sputum: performances of the Xpert MTB/RIF ultra compared to the Xpert MTB/RIF, and IS6110 PCR.

The Xpert MTB/RIF Ultra assay has recently been launched to improve the detection of smear negative disease. This retrospective study compares the sensitivity of Xpert MTB/RIF Ultra with that of Xpert MTB/RIF tests and IS6110 real-time PCR in sputum. Diagnostic performance of three molecular tests was evaluated using 48 culture-positive clinical respiratory specimens diluted to obtain paucibacillary sputum specimens. Xpert MTB/RIF Ultra had the highest sensitivity of 100% compared to 42% (P < 0.001) for Xpert MTB/RIF and 64.5% (P = 0.02) for IS6110-PCR. All "very low" or "low" positive specimens using Xpert MTB/RIF Ultra were tested positive using IS6110-PCR, but 35.4% were found negative using Xpert MTB/RIF. Xpert MTB/RIF Ultra is more sensitive than the two other tests for sputum with a low bacterial load. Adding detection of IS6110 and IS1081 to rpoB, is a key evolution of the assay and improves the detection of Mycobacterium tuberculosis' DNA in paucibacillary sputum.

Germline mutation p.N363K in POLE is associated with an increased risk of colorectal cancer and giant cell glioblastoma.

Germline mutations of the POLE gene are responsible for polymerase proofreading-associated polyposis syndrome (PPAP). These mutations were hypothesised to predispose to extra-gastrointestinal tumours (ovary, endometrium, brain), but this association has not been confirmed so far. We report a family with an autosomal dominant inheritance of PPAP due to a c.1089C>A; p.Asn363Lys mutation in the proofreading exonuclease domain of POLE. Ten patients presenting a history of colorectal tumours and three patients with polyposis are indexed in this family. Three carriers (including siblings and a distant cousin at 30, 45 and 52 respectively) and another member (at 37 not tested) presented glioblastoma. This is the second family reported to carry this mutation. Among the four glioblastomas in the family that we report, both show similar pathology: giant cell glioblastoma. These cases suggest that the c.1089C>A germline POLE mutation may confer an increased risk of brain cancer [incidence 17.4% (4/23) in mutation carriers combining the two families]. More observations are needed to support this hypothesis. It seems that not all mutations of POLE are equally associated with extra-gastrointestinal tumours. Although carriers of a mutation responsible for PPAP should benefit from screening for colorectal and uterine cancer, due to the rapid evolution of glioblastoma the value of neurological follow-up and brain imaging screening remains questionable. Nevertheless, considering the limitations of standard therapy for glioblastoma, mutation status could be useful for targeting therapy. The biological mechanism linking POLE mutation to glioblastoma remains to be determined.

Switching from abacavir/lamivudine plus nevirapine to abacavir/lamivudine/dolutegravir in virologically controlled HIV-infected adults (SWAD study).

INTRODUCTION: The metabolic pathways of dolutegravir suggest a potential predator effect of nevirapine on dolutegravir pharmacokinetics and switching from a nevirapine- to a dolutegravir-containing regimen could lead to a lower and suboptimal exposure to dolutegravir several weeks after the switch in case of persistent inducer effect. PATIENTS AND METHOD: Prospective, pilot, single-arm, open-label, non-comparative, bicentric study to evaluate the pharmacokinetics, virologic outcomes, safety, and patient satisfaction of switching from abacavir/lamivudine and nevirapine to a single tablet of abacavir/lamivudine/dolutegravir. The primary endpoint was the maintenance of virologic suppression (HIV-1 RNA<50 copies/mL) at week 12. Secondary endpoints were virologic suppression at week 48, safety and tolerability, patient satisfaction, and pharmacokinetic interaction between nevirapine and dolutegravir. Fifty-three adults on stable abacavir/lamivudine and nevirapine regimen for a median duration of 6years and virologically suppressed for 9.6years were included. RESULTS: Dolutegravir reached steady state by week 4/week 12 when expected by day 5/day 10. All subjects maintained plasma HIV-RNA˂50 copies/mL at week 12 and week 48. Abacavir/lamivudine/dolutegravir was well-tolerated, with two cases of serious adverse events deemed unrelated to study drugs (coronary syndrome in both cases), and one discontinuation for renal impairment at week 24 with a slight improvement after dolutegravir discontinuation. Level of treatment satisfaction remained high after the switch. CONCLUSION: The transient predator effect of nevirapine on dolutegravir had no clinical consequences after switching from nevirapine to dolutegravir, neither on safety nor maintenance of virologic suppression. It also had no consequences on patient satisfaction.

Effect of HIV-1 and antiretroviral therapy on herpes simplex virus type 2: a prospective study in African women.

OBJECTIVES: To document the natural history of herpes simplex virus type 2 (HSV-2) in relation to HIV and highly active antiretroviral therapy (HAART) in Africa, a longitudinal study was conducted of women in the placebo arms of two randomised controlled trials of HSV-suppressive therapy in Burkina Faso. METHODS: 22 HIV-uninfected women (group 1), 30 HIV-1-infected women taking HAART (group 2), and 68 HIV-1-infected women not eligible for HAART (group 3) were followed over 24 weeks. HSV-2 DNA was detected on alternate weeks using real-time PCR from cervicovaginal lavages. Plasma HIV-1 RNA was measured every month. CD4 cell counts were measured at enrollment. RESULTS: Ulcers occurred on 1.9%, 3.1% and 7.2% of visits in groups 1, 2 and 3 (p = 0.02). Cervicovaginal HSV-2 DNA was detected in 45.5%, 63.3% and 67.6% of women (p = 0.11), and on 4.3%, 9.7% and 15.5% of visits in the three groups (p<0.001). Among HIV-infected women, cervicovaginal HSV-2 DNA was detected more frequently during ulcer episodes (adjusted risk ratio (aRR) 2.79, 95% CI 2.01 to 3.86) and less frequently among women practising vaginal douching (aRR 0.60, 95% CI 0.40 to 0.91). Compared with women not taking HAART and with CD4 cell counts of 500 cells/microl or greater, women on HAART had a similar risk of HSV-2 shedding (aRR 0.95, 95% CI 0.52 to 1.73), whereas women with CD4 cell counts of 200-500 cells/microl were more likely to shed HSV-2 (aRR 1.71, 95% CI 1.02 to 2.86). CONCLUSIONS: HSV-2 reactivations occur more frequently among HIV-infected women, particularly those with low CD4 cell counts, and are only partly reduced by HAART. HSV therapy may benefit HIV-infected individuals during HAART.

Longitudinal effect following initiation of highly active antiretroviral therapy on plasma and cervico-vaginal HIV-1 RNA among women in Burkina Faso.

BACKGROUND: Highly active antiretroviral therapy (HAART) could decrease HIV-1 transmissibility by reducing genital and plasma HIV-1 RNA. METHODS: We evaluated the effect of HAART on genital and plasma HIV-1 RNA in a cohort of 39 antiretroviral-naïve women in Burkina Faso. Cervico-vaginal lavages were collected before HAART initiation and at six visits over 28 weeks while on HAART. Blood samples were collected at baseline and at three and four visits for CD4 and plasma HIV-1 RNA measurements, respectively. RESULTS: Before HAART, 72% of women had detectable genital HIV-1 RNA. After 18 weeks on HAART, only one woman (2.5%) had detectable plasma HIV-1 RNA and two women (5.1%) had detectable genital HIV-1 RNA. Similar results were observed at each follow-up visit. However, 16/34 (47%) women with consistently undetectable plasma HIV-1 RNA shed HIV-1 at least once between weeks 18 and 28. In samples with detectable genital HIV-1, the mean quantity of HIV-1 RNA decreased from 3.87 prior to HAART to 3.04 log(10) copies/mL at last visit (median 29 weeks; a 6.8-fold decrease in absolute number of copies/mL) (p = 0.04). A significant median CD4 lymphocyte cell gain of 121 cells/muL (interquartile range 59 to 204) was measured between pre-HAART and last visit. CONCLUSION: These findings suggest that HAART could play a role in reducing HIV transmission in Africa; however, they underscore the need to emphasise safe sex practices with patients taking HAART.

Comprehensive proteomic analysis of the human milk proteome: contribution of protein fractionation.

In-depth analysis of the milk proteome by mass spectrometry is challenged by the presence of few high-abundance proteins that interfere with the detection of lower-abundance proteins. Here, we evaluated the proteomic analysis of milk samples following a strong anion exchange fractionation procedure using denaturating conditions ensuring the disruption of protein-protein interactions. Crude whey or skim milk and their different resulting fractions were analyzed by protein chip array mass spectrometry. Using protein chip array mass spectrometry, several high-abundance proteins were localized in distinct fractions increasing the total number of unique peptides and proteins detected. This total number increased by about 20-30% by combining different chromatographic surface arrays used for capture. Reproducible results were obtained in human skim milk and whey; however this approach was not successful with milk fat globule membrane and required refinement. Hence, milk profiling by anion exchange fractionation combined to protein chip array mass spectrometry represents a promising tool to detect unknown low-abundance milk proteins that may ultimately prove useful as biomarkers of diseases transmitted by breastfeeding.

4q25 microdeletion encompassing PITX2: A patient presenting with tetralogy of Fallot and dental anomalies without ocular features.

Axenfeld-Rieger syndrome (ARS) is a heterogeneous clinical entity transmitted in an autosomal dominant manner. The main feature, Axenfeld-Rieger Anomaly (ARA), is a malformation of the anterior segment of the eye that can lead to glaucoma and impair vision. Extra-ocular defects have also been reported. Point mutations of FOXC1 and PITX2 are responsible for about 40% of the ARS cases. We describe the phenotype of a patient carrying a deletion encompassing the 4q25 locus containing PITX2 gene. This child presented with a congenital heart defect (Tetralogy of Fallot, TOF) and no signs of ARA. He is the first patient described with TOF and a complete deletion of PITX2 (arr[GRCh37]4q25(110843057-112077858)x1, involving PITX2, EGF, ELOVL6 and ENPEP) inherited from his ARS affected mother. In addition, to our knowledge, he is the first patient reported with no ocular phenotype associated with haploinsufficiency of PITX2. We compare the phenotype and genotype of this patient to those of five other patients carrying 4q25 deletions. Two of these patients were enrolled in the university hospital in Toulouse, while the other three were already documented in DECIPHER. This comparative study suggests both an incomplete penetrance of the ocular malformation pattern in patients carrying PITX2 deletions and a putative association between TOF and PITX2 haploinsufficiency.

Safety of sofosbuvir-based regimens after liver transplantation: longitudinal assessment of renal function in the prospective ANRS CO23 CUPILT study.

BACKGROUND: In liver transplant recipients with hepatitis C virus recurrence, there is concern about renal safety of sofosbuvir-based regimens. Changes in serum creatinine or in the estimated glomerular filtration rate (eGFR) under treatment are used to look for possible renal toxicity. However, serum creatinine and eGFR are highly variable. AIM: To analyse renal function trajectory with numerous assays of serum creatinine over a long period of time. METHODS: In a multicentre cohort of 139 patients, the eGFR was obtained from serum creatinine using the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation. Slopes of eGFR were defined as a change in eGFR during a period divided by time. Pre-treatment, on-treatment and post-treatment periods were 9 months, 3-9 months and 4.5 months. Interactions between eGFR slopes and the pre-treatment eGFR, use of ribavirin or mycophenolate mofetil, and stage of fibrosis were addressed. On-treatment eGFR slopes were separated in tertiles. Pre- and post-treatment eGFR slopes were compared globally and according to tertiles. RESULTS: The post-treatment eGFR slope was significantly better than pre-treatment eGFR slope (+0.18 (IQR -0.76 to +1.32) vs -0.11 (IQR -1.01 to +0.73) mL/min/1.73 m2 /month, P = 0.03) independently of the pre-treatment eGFR (P = 0.99), ribavirin administration (P = 0.26), mycophenolate mofetil administration (P = 0.51) and stage of fibrosis (F3 and F4 vs lower stages, P = 0.18; F4 vs lower stages, P = 0.08; F4 Child-Pugh B and C vs lower stages, P = 0.38). Tertiles of on-treatment eGFR slopes were -1.71 (IQR -2.54 to -1.48), -0.78 (IQR -1.03 to -0.36) and +0.75 (IQR +0.28 to +1.47) mL/min/1.73 m2 /month. Pre- and post-treatment eGFR slopes were not significantly different according to tertiles (respectively, P = 0.34, 0.08, 0.73). CONCLUSION: The eGFR varies during treatment and gives a confusing picture of the renal safety of sofosbuvir-based regimens. In contrast, longitudinal assessment of the eGFR shows a rising trajectory over longer time, meaning that these therapies are safe for the kidneys in our cohort of liver transplant recipients.

Staging of recent HIV-1 infection using Geenius rapid confirmatory assay compared to INNO-LIA, New Lav and Blot 2.2 assays.

BACKGROUND: Besides confirmation of HIV seropositivity, Western Blot (WB) assays play an important role for identification of recent infection based on incomplete antibody reactivity and lack of p31 band. OBJECTIVES: We evaluated the capacities of the Geenius™ HIV1/2 Confirmatory Assay (Bio-Rad), a new generation rapid confirmatory assay based on immune-chromatography and automated reading, for staging of HIV-1 infection. STUDY DESIGN: Sixteen samples collected during early HIV-1 infections (Fiebig stage III-VI) were tested using the Geenius assay, and compared to HIV Blot 2.2 WB assay (MP Diagnostics), New Lav Blot I WB assay (Bio-Rad) and INNO-LIA™ HIV I/II Score Dot Blot assay (Fujirebio). Results obtained with Geenius and INNO LIA in 47 newly diagnosed chronic HIV-1 infections were also compared. RESULTS: The p24 band was less frequently detected in early HIV-1 infections using the Geenius (3/16) compared to the New Lav (15/16, p<0.0001), INNO-LIA (13/16, p=0.0011), and Blot 2.2 (13/16, p=0.0011). Testing samples collected during chronic infection allowed to confirm that p31 band and complete Gag, Pol, Env profiles were less frequently observed using the Geenius assay compared to the INNO LIA assay (p=0.027 for p31, and p=0.0015 for complete profile). CONCLUSIONS: The Geenius assay is a simple and rapid test showing a high sensitivity to detect Env bands and to confirm HIV-1 seropositivity during the early phases of infection. However, this test is less suitable for distinguishing between later stages of acute and chronic infections because of a reduced sensitivity to detect the p31 and p24 bands compared to INNO LIA and New Lav assays.