Optimal staging and evaluation of residual lesions of invasive fungal infections (IFIs) are major challenges in the immunocompromised host. Preliminary data have suggested that 18Ffluorodeoxyglucose ...(18FFDG) uptake may be observed in the course of active invasive fungal infections. The aim of this study was to assess the role of positron emission tomography with 18FFDG (18FFDG-PET) in the diagnosis and staging of IFI. A prospective monocentric study evaluating 18FFDG-PET in 30 consecutive adults and children with European Organization for Research and Treatment of Cancer/Mycoses Study Group probable or proven IFI was performed. Twenty males and ten females (median age, 45 years (range 6–75 years)) were enrolled. Twenty-six were immunocompromised, as follows: haematological malignancy (18) with allogeneic stem cell transplantation (16/18), solid tumour (three), solid organ transplantation (two), diabetes mellitus (two) and cystic fibrosis (one). IFIs were acute invasive aspergillosis (ten), chronic disseminated candidiasis (ten), zygomycosis (two), black grains eumycetoma (two), pulmonary Histoplasma capsulatum var. capsulatum histoplasmosis (two), and Phomopsis sp. osteoarthritis, Scedosporium apiospermum and Candida krusei spondylodiscitis, and acute pulmonary coccidioidomycosis in one case each. An increased uptake of 18FFDG was observed in all areas previously identified by computed tomography and/or magnetic resonance imaging to be involved by IFI. In 4/10 chronic disseminated candidiasis cases, 18FFDG-PET revealed small splenic abscesses that were unapparent on the corresponding computed tomography scan. 18FFDG uptake disappeared after 6 months of antifungal therapy in three patients with chronic disseminated candidiasis for whom the 18FFDG-PET was performed to assess the evolution of the disease. 18FFDG-PET could potentially be useful for the initial diagnosis and staging of IFI. Whether or not 18FFDG-PET might be useful for assessing the optimal duration of IFI therapy should now be assessed in a specific prospective study.
Kidney transplantation is now considered as a reasonable option for HIV‐infected patients with end‐stage renal disease. We describe here a retrospective study conducted in five transplantation ...centers in Paris. Twenty‐seven patients were included. Immunosuppressive protocol associated an induction therapy and a long‐term treatment combining mycophenolate mofetil, steroids and either tacrolimus or cyclosporine. All the patients had protocol biopsies at 3 months and 1 year. Patient's survival was 100% at 1 year and 98% at 2 years. Graft survival at 1 and 2 years is 98% and 96% at 1 and 2 years, respectively. The mean glomerular filteration rate values at 12 and 24 months were 60.6 mL/min/1.73 m2 (range 23–98) and 65.4 mL/min/1.73m2 (range 24–110), respectively. Acute cellular rejection was diagnosed in four cases (15%). Because of high trough levels of calcineurin inhibitor, protease‐inhibitor therapies were withdrawn in 11 cases. HIV disease progression was not observed. One patient developed B‐cell lymphoma.
In conclusion, our study confirms the safety of renal transplantation in HIV‐infected patients with few adverse events and a low incidence of acute rejection.
Systematic protocol biopsies performed in a cohort of 27 HIV‐infected recipients reveal a low incidence of acute rejection.
STUDY QUESTION
Are antiretroviral therapies associated with semen alterations in HIV-infected men?
SUMMARY ANSWER
Antiretroviral regimens that included the non-nucleosidic reverse transcriptase ...inhibitor efavirenz were associated with a significant impairment of sperm motility, whereas regimens without efavirenz were not associated with significant semen changes.
WHAT IS KNOWN ALREADY
Semen alterations including decreased ejaculate volume and sperm motility have been reported in HIV-infected men. The hypothesis ascribing reduced sperm motility to damages induced in sperm mitochondria by nucleosidic (or nucleotidic) reverse transcriptase inhibitors (NRTIs) has not been confirmed in HIV-infected patients and the effects of antiretroviral treatments on semen parameters remain unclear.
STUDY DESIGN, SIZE, DURATION
This case–control study compared semen characteristics across 378 HIV-1 infected patients receiving different antiretroviral regimens or never treated by antiretroviral drugs, in whom an initial semen analysis was done between 2001 and 2007.
PARTICIPANTS/MATERIALS, SETTING, METHODS
The patients were partners from serodiscordant couples requesting medical assistance to procreate safely. Their status with regard to antiretroviral therapy at the time of semen analysis was categorized as follows: 1/ never treated patients (n = 66); 2/ patients receiving NRTIs only (n = 49); 3/ patients receiving a NRTIs + protease inhibitor (PI) regimen (n = 144); 4/ patients receiving a NRTIs + non-nucleosidic reverse transcriptase inhibitor (NNRTI) regimen (n = 119). Semen parameters were assessed through standard semen analysis. Additional analyses included measurement of sperm motion parameters using computer-assisted semen analysis, seminal bacteriological analysis, seminal biochemical markers and testosterone plasmatic levels. All analyses were performed in the Cochin academic hospital. The data were analyzed through multivariate analysis.
MAIN RESULTS AND THE ROLE OF CHANCE
Sperm motility was the only semen parameter which significantly varied according to treatment status. The median percentage of rapid spermatozoa was 5% in the group of patients receiving a regimen including efavirenz versus 20% in the other groups (P < 0.0001). Accordingly, sperm velocity was reduced by about 30% in this group (P < 0.0001). The role of chance was minimized by the strict definition and the size of the study population, which included a large enough group of never treated patients, the controlled conditions of semen collection and analysis, the multivariate analysis, the specificity and the high significance level of the observed differences.
LIMITATIONS, REASONS FOR CAUTION
The design of the study did not allow demonstrating a causal link between exposure to efavirenz and sperm motility.
WIDER IMPLICATIONS OF THE FINDINGS
As efavirenz is widely used in current antiretroviral therapy, these findings may concern many HIV-infected men wishing to have children. This justifies further assessment of the consequences on fertility of the exposure to efavirenz. Moreover, the possibility of common cellular impacts underlying adverse effects of efavirenz in sperm cells and neurons deserved investigation.
STUDY FUNDING/COMPETING INTEREST(S)
No external funding was used for this study. None of the authors has any conflict of interest to declare.
Vitamine D et pathologies infectieuses Viard, J.-P.
Médecine nucléaire : imagerie fonctionelle et métabolique,
October 2015, 2015-10-00, Letnik:
39, Številka:
5
Journal Article
Recenzirano
Le rôle important que joue la vitamine D dans la régulation des réponses immunes est de plus en plus reconnu. Schématiquement, elle active l’immunité innée et régule négativement l’immunité ...adaptative. Ses actions sur la réponse anti-infectieuse peuvent donc se situer à différents niveaux. Plusieurs études épidémiologiques ont relié le déficit en vitamine D à un risque accru d’acquisition d’infections aiguës comme la tuberculose ou les infections respiratoires hautes ou basses. Dans des infections chroniques, caractérisées par une activation immune persistante et, en particulier, au cours de l’infection par le VIH, le déficit en vitamine D est lié à une activité inflammatoire plus importante qui pourrait expliquer l’association avec une évolution clinique défavorable. Les essais d’intervention testant la supplémentation en vitamine D dans ce contexte ne sont pas encore très nombreux, mais ne sont pas toujours concluants : difficiles à construire, ils sont également difficiles à interpréter. Cet article propose quelques clés pour mieux comprendre cette thématique complexe.
Vitamin D is increasingly recognized as an important immune regulator. Schematically, vitamin D is a stimulator of innate immunity and a negative regulator of adaptive immunity. Its effects on anti-infectious responses may therefore be varied. Several epidemiological studies have linked vitamin D deficiency with the susceptibility to different acute infections, such as tuberculosis and upper and lower respiratory tract infections. In chronic infectious diseases characterized by an ongoing immune activation, in particular in HIV infection, vitamin D deficiency has been linked to increased inflammation, which could explain its association with poorer clinical outcomes. Few intervention trials have tested the effects of vitamin D supplementation in infectious diseases and the results were not always convincing. This article proposes a few guidelines that may help interprete these complex data.
Influence of age on the CD4 cell response to highly active antiretroviral therapy (HAART) was examined in 1956 patients (median age, 37.2 years) in the EuroSIDA study. Median initial CD4 cell count ...was 192×106 cells/L, follow-up was 31 months, and time to maximum CD4 cell response was 20 months. Age groups were not different for baseline CD4 cell count, baseline human immunodeficiency virus RNA load, or treatment history. CD4 cell increase, stratified by age quartiles, differed during months 3–36 of HAART (P=.023). Maximum CD4 cell increase from start of HAART differed by age group (P=.0003), as did maximum CD4 cell count (P<10-4). Multivariate analysis confirmed the inverse relationship between age and maximum CD4 cell response (P=.023). Time to a CD4 increase of >200×106 cells/L was shorter for patients in the younger age groups (P=.0026), as confirmed by multivariate analysis (P<10-4). Younger age may favor CD4 cell restoration because of preserved thymic function
Objective. The purpose of the present study was to determine the prevalence and incidence of virological triple drug-class failure (TCF) and to summarize the clinical outcome for patients who started ...receiving highly active antiretroviral therapy (HAART). Methods. The present study is an observational longitudinal study of 3496 treatment-experienced (TE) and treatment-naive (TN) patients monitored from the time they started receiving HAART (baseline) until TCF occurred (as determined on the basis of viral loads), until AIDS was newly diagnosed, or until death. Results. Four hundred forty-five patients (12.7%) had TCF; 370 (16.6%) of 2230 patients were TE, and 75 (5.9%) of 1266 patients were TN. At 6 years after starting HAART, 21.4% of TE and 11.2% of TN patients had TCF (P < .0001). The prevalence of TCF at or after 2002 was 15.5% in TE patients and 4.8% in TN patients. TN patients had a 32% annual increase in the incidence of TCF (95% confidence interval CI, 14%–54%; P < .0001); at 5 years after starting HAART, the rate was comparable for TE and TN patients (3.3 and 3.4 cases/100 person-years of follow-up PYFU, respectively). The incidence of new cases of AIDS or death was 2.7 cases/100 PYFU in patients who did not experience TCF and 5.0 cases/100 PYFU in patients who did experience TCF, an estimated 36% increase with each category of TCF (95% CI, 19%–56%; P < .0001). Conclusion. The prevalence of TCF was low after patients started receiving HAART, particularly among TN patients. Despite the influx of patients who had started receiving HAART more recently, the prevalence of TCF increased over calendar time. Patients with TCF had a higher incidence of newly diagnosed AIDS or death. Treatment of patients with TCF deserves further investigation.
Immune reconstitution inflammatory syndrome (IRIS) has rarely been described in the course of disseminated cryptococcosis in solid organ transplant recipients. We report here the case of a renal ...transplant recipient who developed severe cellulitis in the context of Cryptococcus neoformans‐associated IRIS while undergoing reduction of his immunosuppressive therapy. IRIS appeared concomitantly with a dramatic increase of blood CD4+ T cells (94–460/mm3) and required the administration of a short‐term steroid therapy to resolve.
This renal transplant recipient developed severe cellulitis in the context of Cryptococcus neoformans‐associated IRIS while undergoing reduction of his immunosuppressive therapy and required the administration of a short‐term steroid therapy to resolve.
Background. Low 25-hydroxyvitamin D (25(OH)D) has been associated with inflammation, human immunodeficiency virus (HIV) disease progression, and death. We aimed to identify the prognostic value of ...25(OH) D for AIDS, non-AIDS-defining events and death, and its association with immunological/inflammatory markers. Methods. Prospective 1-1 case-control study nested within the EuroSIDA cohort. Matched cases and controls for AIDS (n = 50 matched pairs), non-AIDS-defining (n = 63) events and death (n = 41), with plasma samples during follow-up were selected. Conditional logistic regression models investigated associations between 25(OH)D levels and annual 25(OH)D change and the probability of events. Mixed models investigated relationships between 25(OH) D levels and immunological/inflammatory markers. Results. In sum, 250 patients were included. Median time between first and last sample and last sample and event was 44.6(interquartile range IQR: 22.7-72.3) and 3.1(IQR: 1.4-6.4) months. Odds of death decreased by 46.0%(95% confidence interval CI, 2.0-70.0, P= .04) for a 2-fold increase in latest 25(OH) D level. There was no association between 25(OH) D and the occurrence of AIDS or non-AIDS-defining events (P >.05). In patients with current 25(OH) D < 10 ng/mL, hsIL-6 concentration increased by 4.7%(95% CI, .2,9.4, P =.04) annually after adjustment for immunological/inflammatory markers, and no change in hsCRP rate was observed (P =.76). Conclusions. Low Vitamin D predicts short term mortality in HIV-positive persons. Effectiveness of vitamin D supplementation on inflammation and patient outcomes should be investigated.
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