Amandine Gagneux-Brunon

Performance of creatinine and cystatin C-based glomerular filtration rate estimating equations in a European HIV-positive cohort.

Objective:To validate glomerular filtration rate (GFR) estimating equations in white HIV-infected patients based on serum creatinine and/or serum cystatin C. Design:Single-center, cross-sectional evaluation of the predictive performance of GFR estimators. Methods:GFR was measured by iohexol plasma clearance. Serum creatinine (Scr) and serum cystatin C (Scyst) were measured by traceable and standardized methods. We evaluated the performance of the Modification of Diet in Renal Disease (MDRD) and the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equations. We also studied the performance of the cystatin C-based equation (CKD-EPI Scyst) and the combined cystatin and creatinine-based equation (CKD-EPI combined), as recently proposed by the CKD-EPI group. Results:Two hundred and three participants (18% of women) were included. Mean age was 49 ± 10 years. Mean measured GFR (mGFR) was 95 ± 24 ml/min per 1.73 m2. CKD-EPI and CKD-EPI combined significantly outperformed the MDRD equation. The percentage of estimating results within 30% of mGFR was 75, 82 and 81% for the MDRD, CKD-EPI and CKD-EPI combined equation, respectively. Results favoring the CKD-EPI and CKD-EPI combined equation were especially observed for patients with mGFR over 90 ml/min per 1.73 m2. Conclusion:In our European HIV cohort, we confirmed that the creatinine-based CKD-EPI equation should replace the MDRD study equation. However, global performance of this equation remains worse than the performance observed in the general population. This lesser performance is particularly relevant in patients with measured GFR under and around 60 ml/min per 1.73 m2. Moreover, the specific interest of Scyst-based equations is not confirmed in this population.

Cystatin C in HIV-infected patients: promising but not yet ready for prime time

With the development of highly active antiretroviral therapy, chronic kidney disease has become a prominent cause of morbidity in individuals infected by HIV. Because serum creatinine has significant limitations in this specific population, cystatin C is emerging as a promising biomarker for both the evaluation of glomerular filtration rate (GFR) and the detection of drug-induced kidney injury. Along with renal function, serum cystatin C concentration is associated with several biological parameters such as C-reactive protein, HIV viral load and CD4+ cells count. All these determinants of cystatin C are, however, more or less independent of GFR. Studies evaluating the accuracy of cystatin C for estimating GFR in the setting of HIV infection are scarce and methodology is often questionable (lack of reference method or inadequate statistical analyses). Thus far, data are insufficient to encourage the use of cystatin C or cystatin C-based equations to estimate GFR in the HIV-infected population. Further research is needed to explore the clinical utility of cystatin C in this setting. Beyond the use of cystatin C as a GFR marker, future studies will have to evaluate its role as a predictor of patient outcome, particularly in regard to cardiovascular morbi-mortality.

Anti-N-methyl-D-aspartate receptor encephalitis after Herpes simplex virus-associated encephalitis: an emerging disease with diagnosis and therapeutic challenges.

AbstractIntroductionMorbidity and mortality of Herpes simplex virus encephalitis (HSE) remain high. Relapses of neurological signs may occur after initial clinical improvement under acyclovir treatment.MethodsWe report here a case of post-HSE anti-N-methyl-d-aspartate receptor-mediated encephalitis in an adult and perform a systematic search on PubMed to identify other cases in adults.ResultsWe identified 11 previously published cases, to discuss diagnostic and therapeutic management. Symptoms in adults are often inappropriate behaviors, confusion and agitation. Diagnosis of anti-NMDA-R encephalitis after HSE is often delayed. Treatment consists in steroids, plasma exchange, and rituximab. Prognosis is often favorable.ConclusionAnti-NMDA-R antibodies should be searched in cerebrospinal fluid of patients with unexpected evolution of HSE. This emerging entity reopens the hot debate about steroids in HSE.

NGAL biomarqueur de lésion rénale

Neutrophil Gelatinase Associated Lipocalin (NGAL) is one of the most promising biomarkers for acute kidney injury (AKI). Although urinary NGAL is intuitively more appropriate to apprehend renal injury, clinical data have accumulated on the potential interest of NGAL measured indifferently in serum or urine. Diagnostic performance of NGAL greatly varies across studies according to different factors such as the type of patients (pediatric versus adult) and the clinical situations (surgery versus intensive care). Overall, NGAL is presented as a useful tool to diagnose and predict AKI outcome but several issues (the absence of a unique pertinent threshold value, the incomplete analytical validation of its measurement and, its apparent limited clinical added value as compared to traditional AKI markers) remain to be addressed in order to definitely recommend its use in clinical practice.

Mycoplasma hominis: a rare but true cause of infective endocarditis

ABSTRACT Mycoplasma spp. are rarely recognized agents of infective endocarditis. We report a case of Mycoplasma hominis prosthetic valve endocarditis diagnosed by 16S ribosomal DNA (rDNA) PCR and culture of valves in a 74-year-old man. We reviewed the literature and found only 8 other cases reported.

Pre-travel advice seeking from GPs by travellers with chronic illness seen at a travel clinic

PURPOSE Travellers are ageing and frequently report chronic illness. Pre-travel health advice is crucial, particularly in this subgroup, and general practitioners (GPs) are first in line for treatment adjustment before departure. Our aim is to evaluate pre-travel health advice seeking from GPs by travellers with chronic illness seen at a travel clinic. METHODS A cross-sectional observational survey using a questionnaire was conducted between August 2013 and July 2014 in travellers attending the travel medicine clinic of a tertiary university hospital in France. RESULTS During the study, 2019 travellers were included. Mean age was 39.4 years (±18.8). Three hundred and ninety-one (19.4%) travellers reported a history of a chronic illness. Arterial hypertension and diabetes mellitus were the most frequently reported illnesses, affecting, respectively, 168 (8.3%) travellers and 102 (5.1%). Hajj pilgrims were more likely to report a history of chronic illness than other travellers. Only 810 (40.1%) travellers sought pre-travel advice from their GP. Six hundred and fifty-two (40.1%) healthy travellers and 158 (40.5%) travellers reporting chronic illness sought pre-travel advice from their GP (P = 0.96). CONCLUSION Travellers with a history of chronic illness do not seek pre-travel health advice from their GP more frequently than healthy travellers. Travel health specialists are generally not the best practitioners to manage the care of underlying medical conditions presenting risks during travel. However, GPs offer continuity and disease management expertise to improve the specificity of pre-travel planning. Thus, ongoing collaboration between the traveller, GP and travel health specialist is likely to yield the best outcomes.

Tenosynovitis: a rare presentation of tuberculosis better known by hand surgeons than infectious diseases specialists

PurposeClinical presentation of tuberculosis is pleomorphic. Some forms are rare and better known by surgeons than infectious disease specialists.MethodsWe describe a rare case of isolated chronic tenosynovitis of the wrist due to Mycobacterium tuberculosis in a 66-year-old man and review similar cases in the literature.ResultsOn literature search, only 23 other cases of tuberculous tenosynovitis were retrieved. Our case is similar, with an insidious classical presentation. The diagnosis was suggested at the surgical presentation by the presence of rice body masses.ConclusionThe diagnosis of tuberculous tenosynovitis should be considered in chronic tenosynovitis. Functional prognosis may be committed without adequate treatment.

Persistent But Not Replicating HIV-1 Cell-Associated DNA in Semen of Long-Term ART Experienced Men

BACKGROUND The semen of HIV-1 infected men represents the main vector of HIV-1 spread following sexual transmission of cell-free or cell-associated virions. OBJECTIVE The present study aimed to assess the impact of HAART on HIV-1 RNA/DNA and on inflammatory environment in the semen of long-term HAART-experienced men. METHODS Forty-five paired samples of semen and blood were obtained from 37 consenting men, 10 untreated and 27 under HAART. Blood and seminal HIV RNA and DNA loads were quantified by the Abbott RealTime m2000rt assay and an inhouse real-time PCR protocol, respectively. Tat/rev/nef intra-cellular mRNA was tested by qualitative PCR. Interleukin (IL)- 1β, IL-2, IL-6, IL-7, IL-8, IL-10, GM-CSF and TNFα were quantified in 20 paired samples by Bio-plex® assay. RESULTS No semen was found HIV RNA positive in men under HAART. Twenty-six percent of semen samples from HAART-experienced men remained positive for HIV DNA. Seminal HIV DNA was significantly associated with the duration of infection and the HIV DNA load in blood. No seminal mononuclear cells were found positive for intracellular HIV RNA in HAART experienced men. All the tested chemokines exhibited significantly higher concentration in semen than in blood in both treated and untreated men. No effect of HAART on cytokines/chimiokines loads was observed. CONCLUSION These results demonstrate the efficacy of HAART on the reduction of seminal RNA HIV-1 loads despite the persistence of local inflammation. Moreover, in our hands the seminal cell-associated virus reservoir was not reactivated in an inflammatory environment was not productive and its reactivation seems unlikely.

Preventing long-term tenofovir renal toxicity by pharmacokinetic assessment.

Tenofovir is the active metabolite of tenofovir disoproxil fumarate (TDF), a commonly used antiretroviral agent in HIV treatment and in HIV preexposure prophylaxis. After a long-term exposure, TDF is associated with kidney impairment. In the D:A:D study cohort of HIV-infected patients (22 603 HIV-infected patients with baseline estimated glomerular filtration rate (eGFR) 90 ml/min per 1.73 m), tenofovir exposure was associated after adjustment with an increased relative risk (1.18 a year) of developing chronic kidney disease (CKD) defined by the occurrence of an eGFR below 70 ml/min per 1.73 m [1]. Recent studies also suggested that tenofovir use in preexposure prophylaxis might also be associated with a weak decline in eGFR, a mean decrease in eGFR after 60 months of treatment was 6 ml/min in the Bangkok Tenofovir study [2], and around 2 ml/min per 1.73 m during a median follow-up of 18 months in Partners Prep Study [3]. The decline in eGFR associated with tenofovir use is not always reversible after treatment cessation [4]. Tenofovir has a mitochondrial toxicity in tubular cells, leading to kidney tubular dysfunction (KTD) [5]. KTD affects 10.6–19% of the patients receiving tenofovir [6,7]. Tubular tenofovir toxicity is probably dose dependent. Indeed, an association between high-trough tenofovir plasma concentrations and KTD (defined by hypophosphatemia, hypouricemia, nondiabetic glucosuria, b-2 microglobulinuria, or a-1 microglobulinuria) was previously observed [6,7]. However, a decrease in eGFR may be observed without evidence for KTD. It is crucial to identify mechanisms and risk factors of tenofovir renal toxicity. Tenofovir penetrates in tubular cells by several tubular transporters. Polymorphisms in genes encoding for tubular transporters organic cationic transporter 1, multidrug resistant protein 2 (MRP-2) and 4 (MRP-4) were associated with increased tenofovir plasma concentrations and increased risk of KTD or of decrease in eGFR [8–11].

Vaccine coverage in PLWH: disparities and potential impact of vaccine hesitancy

Dear Editor, We read with great interest the article by Tsachouridou et al. entitled “Factors associated with poor adherence to vaccination against hepatitis viruses, Streptococcus pneumoniae and seasonal influenza in HIV-infected adults”. The authors aimed to identify risk factors for non-adherence to routine vaccination in HIV-infected patients. They evaluated vaccine coverage in 1210 HIV-infected patients against hepatitis A virus (HAV), hepatitis B virus (HBV), seasonal influenza and invasive pneumococcal diseases (IPD). We performed a similar study in our cohort of HIV-infected patients; our aim was to evaluate vaccine coverage for routine vaccinations, and to identify factors associated with poor adherence, particularly patients’ beliefs and attitudes toward vaccines. We included 561 HIV-infected patients, and 468 (83,4%) of them answered a self-questionnaire assessing their beliefs and attitudes towards vaccines. We observed a significantly lower vaccine coverage than Tsachouridou et al. against HAV, HBV, and IPD. In our cohort, vaccine coverage against IPD was 20 % versus 79 % in the Greek cohort. Vaccine coverage for HAV and HBV were respectively 23.7% and 63.5% in our cohort, contrasting with the 73.6% and 73.6% observed in the Greek study. However, vaccine coverage against seasonal influenza was quite similar, 40.1 % in our cohort and 39 % in the Greek cohort. The observed difference in vaccine coverage in people living with HIV between Greece and France are not explained by different guidelines or by costs, as in both countries, all four vaccines are recommended in PLWH and without additional costs for patients. To explain the observed differences, we formulate several hypotheses. First, we can suggest that mistrust in vaccines may contribute to the observed differences. France is the leading country for vaccine hesitancy, and more than 40 % of the French people considered the safety of vaccines as doubtful. In our cohort, 10.3 % of the respondents to the selfquestionnaire declared to be firmly against vaccines. Secondly, in Greece, vaccines are provided free of charge by the hospital to PLWH, in France, vaccines are also provided free of charge for PLWH, but not directly by the hospital, and patients should take vaccines in a pharmacy and vaccines are administered by a physician. This discrepancy between the two systems suggests that active offer of vaccinations inHIV clinicsmayhelp to improve vaccine coverage. Active offer of vaccines during the hospital stay in splenectomized patients and in hospitalized adults was associated with an increase in adherence to vaccination. Tsachouridou et al. observed a negative impact of the 2010 financial crisis on vaccine coverage against HAV, HBV, and pneumococcal disease. They did not observe any difference for the vaccine coverage against seasonal influenza. The absence of impact is probably due to the fact that vaccine coverage against seasonal influenza is very low. The vaccine coverage in Greek PLWH was as low as the vaccine coverage observed in our study. Vaccine coverage against seasonal influenza was also very low in a US Cohort of PLWH around 42 % and in another French cohort of PLWH around 30.9 %. There is a real issue with vaccination against seasonal influenza in PLWH. We suggest that vaccine hesitancy is particularly high for vaccination against seasonal influenza in PLWH. Among the 143 unvaccinated against seasonal influenza responders to our questionnaire, 29 (20.3%) declared to be firmly opposed to this vaccine, 52 (36.4 %) considered vaccine against seasonal influenza as futile, and 19 (13.3 %) were feared about side effects. In univariate analysis, older age and suffering from another comorbidity was associated with a better adherence to seasonal influenza vaccine. In multivariate analysis, only older age remained associated with adherence. Tsachouridou et al. also observed an association between older age and adherence to seasonal influenza vaccine. In contrast, in their cohort, lower level of education and lack of insurance were associated with non adherence. In France, PLWH receive each year a voucher from the National Health Insurance for a free vaccine against seasonal influenza. In our cohort, vaccine coverage against seasonal influenza increased to 68.4 % in patients receiving a piece of information by HIV specialists or general practitioners, and was significantly higher than in patients who only received a voucher. Transient increase in HIV viral load observed after seasonal influenza vaccination was not considered by patients as an issue, only two patients were afraid to observe an increase in HIV viral load. Curiously, 13.3 % patients were feared about side effects of seasonal influenza vaccine. In contrast, only 4 % had fears about side effects of vaccine against pneumococcal disease, whereas more than 50 % of the patients did not get any information about the vaccine against pneumococcal disease. These different observations suggest that the vaccine against seasonal influenza is not considered like another one by the PLWH. In conclusion, efforts are needed to increase vaccine coverage in PLWH, particularly against seasonal influenza and pneumococcal disease. Vaccine hesitancy is probably an