Background: In France, the combination hydroxychloroquine (HCQ) and azithromycin (AZ) is used in the treatment of COVID-19. Methods: We retrospectively report on 1061 SARS-CoV-2 positive tested patients treated for at least three days with the following regimen: HCQ (200 mg three times daily for ten days) + AZ (500 mg on day 1 followed by 250 mg daily for the next four days). Outcomes were death, clinical worsening (transfer to ICU, and > 10 day hospitalization) and viral shedding persistence (> 10 days). Results: A total of 1061 patients were included in this analysis (46.4% male, mean age 43.6 yearsrange 14-95 years). Good clinical outcome and virological cure were obtained in 973 patients within 10 days (91.7%). Prolonged viral carriage was observed in 47 patients (4.4%) and was associated to a higher viral load at diagnosis (p < .001) but viral culture was negative at day 10. All but one, were PCR-cleared at day 15. A poor clinical outcome (PClinO) was observed for 46 patients (4.3%) and 8 died (0.75%) (74-95 years old). All deaths resulted from respiratory failure and not from cardiac toxicity. Five patients are still hospitalized (98.7% of patients cured so far). PClinO was associated with older age (OR 1.11), severity of illness at admission (OR 10.05) and low HCQ serum concentration. PClinO was independently associated with the use of selective betablocking agents and angiotensin II receptor blockers (p < .05). A total of 2.3% of patients reported mild adverse events (gastrointestinal or skin symptoms, headache, insomnia and transient blurred vision). Conclusion: Administration of the HCQ+AZ combination before COVID-19 complications occur is safe and associated with a very low fatality rate in patients.
Tat is a viral protein secreted from HIV infected cells and extra cellular Tat is suspected to prevent destruction of HIV infected cells from cells of the cellular immunity. The effect of anti retroviral therapy (ART) on Tat secretion has never been investigated. In this study, we tested for antibody reactivity against Tat variants representative of the main HIV subtypes in HIV positive patients receiving ART with undetectable viral loads ( < 40 copies/mL) over the course of one year with a blood sampling every three months. For each of theses five blood sampling, an average of 50 % of patients had Anti-Tat IgG, it turned out that 86% of patients could recognize Tat at least in one blood sampling during the course of the study. Amazingly, anti-Tat IgG appeared and/or disappeared in 66 % of patients. Only 20% had anti-Tat IgG remaining persistently while 14% were consistently without anti Tat IgG in the five blood sampling. No significant correlation was found between anti-Tat IgG and CD4+ T cell, CD8+ T cell and B cell counts revealing the incapacity of these anti Tat IgG to neutralize extra cellular Tat. Interestingly the absence and then the appearance of anti-Tat IgG in patients suggest the presence of HIV infected cells in the blood that may constitute a significant reservoir of HIV infected cells. As a conclusion antiretroviral therapy does not block the secretion of Tat and may explain why HIV infected cells can survive in spite of an effective ART treatment.
Hepatitis E virus (HEV) is a newly-identified causative agent of acute and chronic hepatitis in severely immunocompromized patients. The present study sought to assess the prevalences of past, recent, on-going, and chronic HEV infections in patients infected with human immunodeficiency virus (HIV) in Marseille, South-eastern France, and to determine if they were correlated with the patients' immunological status or with cirrhosis. Anti-HEV IgG and IgM and HEV RNA testing were concurrently performed on the plasma from 184 patients infected with HIV, including 81 with a CD4+ T-lymphocyte count (CD4 count) <50 cells/mm(3) and 32 with a cirrhosis. Prevalence of anti-HEV IgG and IgM was 4.4% (8/184) and 1.6% (3/184), respectively. Past, recent, and on-going infections were observed in 3.3% (6/184), 1.6% (3/184), and 0.5% (1/184) of the patients, respectively. Anti-HEV antibodies prevalence did not differ significantly according to CD4 count, cirrhosis, sex, age, mode of HIV transmission, and infection with hepatitis B or C virus. Anti-HEV IgG seroreversion was observed in two patients. The patient whose plasma tested positive for HEV RNA had a CD4 count <50 cells/mm(3) ; HEV genotype was 3f. In this patient, longitudinal testing showed HEV RNA positivity during a 10-month period, indicating chronic HEV infection; in contrast, anti-HEV IgG never tested positive. Further studies are needed to evaluate the performance of commercial HEV serological assays in patients infected with HIV and to assess the actual incidence, prevalence, and outcome of HEV infection in this special group of patients. HEV RNA testing is necessary for such purposes.
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