HIV/SIV Infection Primes Monocytes and Dendritic Cells for Apoptosis

Subversion or exacerbation of antigen-presenting cells (APC) death modulates host/pathogen equilibrium. We demonstrated during in vitro differentiation of monocyte-derived macrophages and monocyte-derived dendritic cells (DCs) that HIV sensitizes the cells to undergo apoptosis in response to TRAIL and FasL, respectively. In addition, we found that HIV-1 increased the levels of pro-apoptotic Bax and Bak molecules and decreased the levels of anti-apoptotic Mcl-1 and FLIP proteins. To assess the relevance of these observations in the context of an experimental model of HIV infection, we investigated the death of APC during pathogenic SIV-infection in rhesus macaques (RMs). We demonstrated increased apoptosis, during the acute phase, of both peripheral blood DCs and monocytes (CD14+) from SIV+RMs, associated with a dysregulation in the balance of pro- and anti-apoptotic molecules. Caspase-inhibitor and death receptors antagonists prevented apoptosis of APCs from SIV+RMs. Furthermore, increased levels of FasL in the sera of pathogenic SIV+RMs were detected, compared to non-pathogenic SIV infection of African green monkey. We suggest that inappropriate apoptosis of antigen-presenting cells may contribute to dysregulation of cellular immunity early in the process of HIV/SIV infection

Déficit en 25 OH vitamine D (prévalence, facteurs de risque et influence de la recharge en cholécalciférol chez les patients infectés par le virus du VIH)

PARIS-BIUP (751062107) / SudocSudocFranceF

Cellules dendritiques plasmacytoides circulantes et primo-infection par le virus de l'immunodéficience humaine (évolution sous traitement antirétroviral chez sept patients)

PARIS-BIUM (751062103) / SudocCentre Technique Livre Ens. Sup. (774682301) / SudocSudocFranceF

Risk of AIDS-defining cancers among HIV-1-infected patients in France between 1992 and 2009: results from the FHDH-ANRS CO4 cohort.

BACKGROUND: We examined trends in the incidence of the 3 AIDS-defining cancers (ADCs; Kaposi sarcoma [KS], non-Hodgkin lymphoma [NHL], and cervical cancer) among human immunodeficiency virus (HIV)-infected patients relative to the general population between 1992 and 2009 in France, focusing on age at ADC diagnosis and on patients with controlled viral load and restored immunity on combination antiretroviral therapy (cART). METHODS: Age- and sex-standardized incidence rates were estimated in patients enrolled in the French hospital database on HIV, and in the general population in France during 4 calendar periods (1992-1996, 1997-2000, 2001-2004, and 2005-2009). Standardized incidence ratios (SIRs) were calculated for all periods and separately for patients on cART, with CD4 counts ≥500 cells/µL for at least 2 years and viral load ≤500 copies/mL. RESULTS: Although the incidence of ADCs fell significantly across the calendar periods, the risk remained constantly higher in HIV-infected patients than in the general population. In patients with restored immunity, the relative risk remained significantly elevated for KS (SIR = 35.4; 95% confidence interval [CI], 18.3-61.9), and was similar to that of the general population for NHL (SIR = 1.0; 95% CI, .4-1.8). ADCs were diagnosed at a younger age in HIV-infected patients, with a particularly marked difference for NHL (-11.3 years, P < .0001). CONCLUSIONS: The incidence of all ADCs continued to fall, including cervical cancer, in the cART period, but the risk remained higher than in the general population in 2005-2009. In patients with stably restored immunity, KS remained significantly more frequent than in the general population

Subcutaneous ivermectin as a safe salvage therapy in Strongyloides stercoralis hyperinfection syndrome : A case report

International audienceStrongyloides stercoralis hyperinfection syndrome due to the acceleration of the autoinfective cycle of the nematode is a life-threatening form of the infection occurring in immunocompromised hosts. Intestinal ileus, which is commonly encountered in this form, may reduce the bioavailability and thus the efficacy of oral anthelminthic drugs used in the treatment of the S. stercoralis hyperinfection syndrome. We report the efficacy and safety of subcutaneous administration of ivermectin in a patient infected with human T cell lymphotropic virus type I with S. stercoralis hyperinfection syndrome who was unresponsive to an oral combination of ivermectin and albendazole

The Spectrum of Chronic CD8 T-Cell Expansions: Clinical Features in 14 Patients

International audienceChronic CD8 + T-cell expansions can result in parotid gland swelling and other organ infiltration in HIV-infected patients, or in persistent cytopenias. We report 14 patients with a CD8 + T-cell expansion to better characterize the clinical spectrum of this ill-defined entity. Patients (9 women/5 men) were 65 year-old (range, 25–74). Six patients had $1 symptomatic organ infiltration, and 9 had$1 cytopenia with a CD8 + (.50% of total lymphocyte count) and/or a CD8 + /CD57 + (.30% of total lymphocyte count) T-cell expansion for at least 3 months. One patient had both manifestations. A STAT3 mutation, consistent with the diagnosis of large granular lymphocyte leukemia, was found in 2 patients with cytopenia. Organ infiltration involved lymph nodes, the liver, the colon, the kidneys, the skin and the central nervous system. Three patients had a HIV infection for 8 years (range, 0.5–20 years). Two non-HIV patients with hypogammaglobulinemia had been treated with a B-cell depleting monoclonal antibody (rituximab) for a lymphoma. One patient had a myelodysplastic syndrome with colon infiltration and agranulocytosis. The outcome was favorable with efficient antiretroviral therapy and steroids in HIV-infected patients and intravenous immunoglobulins in 2/3 non-HIV patients. Six patients had an agranulocytosis of favorable outcome with granulocyte-colony stimulating factor only (3 cases), cyclophosphamide, methotrexate and cyclosporine A, or no treatment (1 case each). Three patients had a pure red cell aplasia, of favorable outcome in 2 cases with methotrexate and cyclosporine A; one patient was unresponsive. Chronic CD8 + T-cell expansions with organ infiltration in immunocompromised patients may involve other organs than parotid glands; they are non clonal and of favorable outcome after correction of the immune deficiency and/or steroids. In patients with bone marrow infiltration and unexplained cytopenia, CD8 + T-cell expansions can be clonal or not; their identification suggests that cytopenias are immune-mediated. Our results extend the clinical spectrum of chronic CD8 + T-cell expansions

HIV-associated kidney glomerular diseases: changes with time and HAART.

International audienceBACKGROUND: Treatment and co-morbidities of human immunodeficiency virus (HIV)-infected individuals have changed dramatically in the last 20 years with a potential impact on renal complications. Our objective was to assess the change in distribution of the glomerular diseases in HIV patients. METHODS: We retrospectively analysed demographic, clinical, laboratory and renal histopathological data of 88 HIV-infected patients presenting with a biopsy-proven glomerular disease between 1995 and 2007. RESULTS: In our study including 66% Black patients, HIV-associated nephropathy (HIVAN) was observed in 26 cases, classic focal segmental glomerulosclerosis (FSGS) in 23 cases, immune complex glomerulonephritis in 20 cases and other glomerulopathies in 19 patients. HIVAN decreased over time, while FSGS emerged as the most common cause of glomerular diseases (46.9%) in HIV-infected individuals undergoing kidney biopsy in the last 2004-07 period. Patients with HIVAN were usually Black (97%), with CD4 <200/mL (P = 0.01) and glomerular filtration rate <30 mL/min/1.73 m(2) (P < 0.01). Compared to HIVAN, patients with classic FSGS were less often Black (P < 0.01), have been infected for longer (P = 0.03), were more often co-infected with hepatitis C virus (P = 0.05), showed more often cardiovascular (CV) risk factors (P < 0.01), had less often CD4 <200/mL (P = 0.01), lower HIV viral load (P = 0.01) and tended to be older (P = 0.06). CONCLUSIONS: Classic FSGS associated with metabolic and CV risk factors has overcome HIVAN in HIV-infected patients. Compared with other glomerulopathies, HIVAN remains strongly associated with severe renal failure, Black origin and CD4 lower than 200/mL at presentation

Emerging RNA-Dependent RNA Polymerase Mutation in a Remdesivir-Treated B-cell Immunodeficient Patient With Protracted Coronavirus Disease 2019

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly discovered virus for which remdesivir is the only antiviral available. We report the occurrence of a mutation in RdRP (D484Y) following treatment with remdesivir in a 76-year-old female with post-rituximab B-cell immunodeficiency and persistent SARS-CoV-2 viremia. A cure was achieved after supplementation with convalescent plasma