Post-traumatic stress among COVID-19 survivors: A descriptive study of hospitalized first-wave survivors.

Introduction: The coronavirus Severe Acute Respiratory Syndrome Coronavirus Type 1 induces a severe respiratory disease, coronavirus disease 2019 (COVID-19). After Severe Acute Respiratory Syndrome Coronavirus Type 1 and Middle East Respiratory Syndrome infection, increased post-traumatic stress disorder (PTSD) rates were described. Methods: This single-centred, prospective study aimed to evaluate the rates of PTSD in patients who were hospitalized for COVID-19. Inclusion criteria were COVID-19 patients hospitalized in the intensive care unit (ICU) or in a standard unit with at least 2 L/min oxygen. Six months post-hospitalization, subjects were assessed for PTSD using a validated screening tool, the Post-Traumatic Stress Checklist-5 (PCL-5). Results: A total of 40 patients were included. No demographic differences between the ICU and non-ICU groups were found. The mean PCL-5 score for the population was 8.85±10. The mean PCL-5 score was 6.7±8 in the ICU group and 10.5±11 in the non-ICU group (P=0.27). We screened one patient with a positive PCL-5 score and one with a possible PCL-5 cluster score. Nine patients had a PCL-5 score of up to 15. Seven patients reported no symptoms. Seven patients accepted a psychological follow-up: one for PTSD, three for possible PTSD and three for other psychological problems. Discussion: The PCL-5 tool can be used by lung physicians during consultations to identify patients for whom follow-up mental health assessment and treatment for PTSD are warranted. Conclusion: Lung physicians should be aware of the risk of PTSD in patients hospitalized for COVID-19 and ensure appropriate screening and follow-up care.

Rapid resistance detection is reliable for prompt adaptation of isoniazid resistant tuberculosis management.

Objectives: Appropriate tuberculosis (TB) management requires anti-TB drugs resistance detection. We assessed the performance of rapid resistance detection assays and their impact on treatment adaptation, focusing on isoniazid resistant (Hr) TB. Methods: From 2016 to 2022, all TB cases enrolled in 3 hospitals were reviewed for phenotypic drug susceptibility testing (p-DST) and genotypic DST (g-DST) performed by rapid molecular testing, and next generation sequencing (NGS). Clinical characteristics, treatment and outcome were collected for Hr-TB patients. The concordance between g-DST and p-DST results, and delay between treatment initiation and results of g-DST and p-DST were respectively recorded to assess the contribution of DST results on Hr-TB management. Results: Among 654 TB cases enrolled, 29 were Hr-TB. Concordance between g-DST by rapid molecular methods and p-DST was 76.9 %, whilst concordance between NGS-based g-DST and p-DST was 98.7 %. Rapid resistance detection significantly fastened Hr-TB treatment adaptation (median delay between g-DST results and treatment modification was 6 days). It consisted in fluoroquinolone implementation for 17/23 patients; outcome was favourable except for 2 patients who died before DST reporting. Conclusion: Rapid resistance detection fastened treatment adaptation. Also, NGS-based g-DST showed almost perfect concordance with p-DST, thus providing rapid and safe culture-free DST alternative.

Low-level viremia is associated with non-B subtypes in patients infected with HIV with virological success following HAART introduction.

This prospective study aimed to determine factors associated with detection of very low-level viremia in patients infected with HIV-1 with virological success following HAART introduction. Fifty-seven patients, mostly (n = 51, 89%) treated with a protease inhibitor-based regimen, were included and followed for 2 years. Viral loads were monitored by Abbott m2000 RealTime HIV-1. Patients were classified as (i) HIV-RNA-negative if viral loads remained strictly undetectable (0 copies/ml), or (ii) HIV-RNA-positive if at least one HIV-1 RNA could be detected in 1-49 copies/ml during follow-up. At month 24, 44 patients (77%) were in the HIV-RNA-positive group, whereas 13 (23%) remained without very low-level viremia. Univariate analysis, Kaplan-Meier curves and the Cox proportional hazard model revealed that B subtype was the only predictor of belonging to the HIV-RNA-negative group (HR 3.98; 95% CI 1.08-14.7). This association needs to be confirmed. Further study of the reservoir and the mechanisms of viral latency according to HIV-subtype will also be necessary to develop new therapeutic strategies and eradicate HIV infection.

Use of covid-19 convalescent plasma to treat patients admitted to hospital for covid-19 with or without underlying immunodeficiency: open label, randomised clinical trial.

Objective: To evaluate the efficacy of covid-19 convalescent plasma to treat patients admitted to hospital for moderate covid-19 disease with or without underlying immunodeficiency (CORIPLASM trial). Design: Open label, randomised clinical trial. Setting: CORIMUNO-19 cohort (publicly supported platform of open label, randomised controlled trials of immune modulatory drugs in patients admitted to hospital with moderate or severe covid-19 disease) based on 19 university and general hospitals across France, from 16 April 2020 to 21 April 2021. Participants: 120 adults (n=60 in the covid-19 convalescent plasma group, n=60 in the usual care group) admitted to hospital with a positive SARS-CoV2 test result, duration of symptoms <9 days, and World Health Organization score of 4 or 5. 49 patients (n=22, n=27) had underlying immunosuppression. Interventions: Open label randomisation to usual care or four units (200-220 mL/unit, 2 units/day over two consecutive days) of covid-19 convalescent plasma with a seroneutralisation titre >40. Main outcome measures: Primary outcomes were proportion of patients with a WHO Clinical Progression Scale score of ≥6 on the 10 point scale on day 4 (higher values indicate a worse outcome), and survival without assisted ventilation or additional immunomodulatory treatment by day 14. Secondary outcomes were changes in WHO Clinical Progression Scale scores, overall survival, time to discharge, and time to end of dependence on oxygen supply. Predefined subgroups analyses included immunosuppression status, duration of symptoms before randomisation, and use of steroids. Results: 120 patients were recruited and assigned to covid-19 convalescent plasma (n=60) or usual care (n=60), including 22 (covid-19 convalescent plasma) and 27 (usual care) patients who were immunocompromised. 13 (22%) patients who received convalescent plasma had a WHO Clinical Progression Scale score of ≥6 at day 4 versus eight (13%) patients who received usual care (adjusted odds ratio 1.88, 95% credible interval 0.71 to 5.24). By day 14, 19 (31.6%) patients in the convalescent plasma group and 20 (33.3%) patients in the usual care group needed ventilation, additional immunomodulatory treatment, or had died. For cumulative incidence of death, three (5%) patients in the convalescent plasma group and eight (13%) in the usual care group died by day 14 (adjusted hazard ratio 0.40, 95% confidence interval 0.10 to 1.53), and seven (12%) patients in the convalescent plasma group and 12 (20%) in the usual care group by day 28 (adjusted hazard ratio 0.51, 0.20 to 1.32). In a subgroup analysis performed in patients who were immunocompromised, transfusion of covid-19 convalescent plasma was associated with mortality (hazard ratio 0.39, 95% confidence interval 0.14 to 1.10). Conclusions: In this study, covid-19 convalescent plasma did not improve early outcomes in patients with moderate covid-19 disease. The efficacy of convalescent plasma in patients who are immunocompromised should be investigated further. Trial registration: ClinicalTrials.gov NCT04345991.

Staphylococcus lugdunensis prosthetic joint infection: A multicentric cohort study.

OBJECTIVES: To describe Staphylococcus lugdunensis prosthetic joint infection (PJI) management and outcome. METHODS: Adults with proven S. lugdunensis PJI were included in a multicentric retrospective cohort. Determinants for failure were assessed by logistic regression and treatment failure-free survival curve analysis (Kaplan-Meier). RESULTS: One hundred and eleven patients were included (median age 72.4 [IQR, 62.7-79.4] years), with a knee (n = 71, 64.0%) or hip (n = 39, 35.1%) PJI considered as chronic in 77 (69.4%) cases. Surgical management consisted in debridement, antibiotic with implant retention (DAIR; n = 60, 54.1%), two-stage (n = 28, 25.2%) or one-stage (n = 15, 13.5%) exchange. Total duration of antimicrobial therapy was 13.1 (IQR, 11.8-16.9) weeks. After a median follow-up of 99.9 (IQR, 53.9-178.1) weeks, 22 (19.8%) S. lugdunensis-related treatment failures were observed. Independent determinants for outcome were diabetes (OR, 3.741; p = 0.036), sinus tract (OR, 3.846; p = 0.032), DAIR (OR, 3.749; p = 0.039) and rifampin-based regimen (OR, 0.319; p = 0.043). Twenty-four (40.0%) of the 60 DAIR-treated patients experienced treatment failure, with hip location (OR, 3.273; p = 0.048), delay from prosthesis implantation (OR, 1.012 per month; p = 0.019), pre-surgical CRP level >115 mg/L (OR, 4.800; p = 0.039) and mobile component exchange (OR, 0.302; p = 0.069) constituting additional determinants of outcome. CONCLUSIONS: Staphylococcus lugdunensis PJI are difficult-to-treat infections, with pivotal roles of an optimal surgical management.

Aspergillus endophthalmitis: Potential role for vitreous galactomannan testing?

Eye damage during invasive aspergillosis is rarely described and biological diagnosis remains challenging. Here we report the case of a heart transplant recipient with ocular aspergillosis complicating disseminated aspergillosis. Although voriconazole was rapidly given, a decrease in visual acuity of the right eye was consistent with endophthalmitis, resulting in an emergency vitrectomy. The diagnosis was rapidly confirmed: laboratory results showed the presence of Aspergillus fumigatus in a vitreous sample. A series of systemic antifungal medications (liposomal amphotericin B, caspofungin, and voriconazole), several liposomal amphotericin B ocular injections, and pars plana vitrectomy resulted in a limited positive clinical outcome. Interestingly although standard mycological follow-up procedures were negative, Aspergillus antigen testing gave an index of 5.92 on vitreous humour, thus a new intraocular injection of liposomal amphotericin B was performed and voriconazole reinitiated. Ten other vitreous samples from patients without fungal infections were also tested, all showing indexes below 0.25. Although larger studies are needed, this case illustrates that galactomannan testing of vitreous humour could be useful for the diagnosis of fungal endophthalmitis if these data are confirmed in other patients, in particular, if standard mycology is negative and PCR is not available.

A severe Mycoplasma pneumoniae pneumonia inducing an acute antibody-mediated pulmonary graft rejection.

A 40-year-old cystic fibrosis woman with a history of double-lung transplantation 2 years previously was admitted for a progressive respiratory distress. Physical examination revealed fever (39°C) and diffuse bilateral lung crackles. Laboratory findings included severe hypoxemia and inflammatory syndrome. Bronchoalveolar lavage and serological test were positive for mycoplasma pneumonia. As the patient did not improve after 3 days of antibiotics and donor-specific HLA antibodies had been detected, an acute antibody-mediated graft rejection was treated with high-dose corticosteroids, plasma exchange, intravenous immunoglobulin, and rituximab. The patient rapidly improved. Unfortunately, 6 months after this episode, she developed a bronchiolitis obliterans syndrome with a dependence to noninvasive ventilator leading to the indication of retransplantation. This case illustrates the possible relationship between infection and humoral rejection. These two diagnoses should be promptly investigated and systematically treated in lung transplant recipients.

Clinical Presentation, Diagnosis, and Bacterial Epidemiology of Peritoneal Tuberculosis in Two University Hospitals in France.

INTRODUCTION: Diagnosis of peritoneal tuberculosis (pTB) is difficult, even in developed countries, where data are lacking. The aim of the present study was to describe the clinical presentation, diagnosis, and bacterial epidemiology of pTB in France over a 10-year period. METHODS: A retrospective study was conducted on pTB in two university hospitals in France, between January 2004 and December 2014. RESULTS: Among the 34 patients, 76.5% were migrants from areas of endemic tuberculosis (TB), mainly Africa. The main presentation (85.3%) was a checkup of ascites or suspicion of peritoneal carcinomatosis. On abdominal computed tomography, ascites was found in 90.6% and peritoneal thickening in 75%. Surgery was required for diagnosis in 58.8% of patients. Six of the patients who did not undergo surgery had ultrasound-guided peritoneal biopsy. Bacteriology was positive for ascites in only 58.1% of cases, for peritoneal biopsy in 73.3%, while granuloma was found in 95.5%. TB polymerase chain reaction (PCR) was positive in 25% of peritoneal biopsy. Mycobacterium bovis was isolated in 23.1% of cases and Mycobacterium tuberculosis in 76.9%. Isolates were fully susceptible (except M. bovis naturally resistant to pyrazinamide). Many (38%) belonged to the lineage T (genetic analysis by spoligotyping). Cure rate was high (76.5%), after a 6-9 months of anti-tuberculous therapy. CONCLUSION: In developed countries, early diagnosis of pTB is still a challenge. Ultrasound-guided peritoneal biopsy may facilitate diagnosis. TB PCR can be useful on peritoneal biopsy. The lineage T was the most prevalent lineage, but more data are required to directly incriminate this lineage in the pathophysiology of pTB.

Persistent production of an integrase-deleted HIV-1 variant with no resistance mutation and wild-type proviral DNA in a treated patient.

An HIV-infected patient presenting an unexpected viral escape under combined antiretroviral treatment is described. The virus isolated from plasma contained a large deletion in the HIV-1 integrase gene but no known resistance mutation. Nested polymerase chain reactions (PCRs) with patient virus integrase-specific primers and probes were developed and used to detect the mutant from plasma, blood, rectal biopsies, and sperm. The variant progressively emerged during a period of therapy-induced virosuppression, and persisted at a low but detectable level for at least 5 years. Surprisingly, proviral DNA from lymphocytes, rectal cells, and sperm cells was, and remained, mainly wild type. Cellular HIV RNA with the deletion was detected only once from the rectum. The origin and mechanisms underlying this so far not described production at a detectable level are largely hypothetical. This observation raised concern about the ability of defective viruses to spread.

Increased Regulatory T-Cell Percentage Contributes to Poor CD4(+) Lymphocytes Recovery: A 2-Year Prospective Study After Introduction of Antiretroviral Therapy.

Background. The primary aim of this study was to determine the impact of regulatory T cells (Tregs) percentage on immune recovery in human immunodeficiency virus (HIV)-infected patients after antiretroviral therapy introduction. Methods. A 2-year prospective study was conducted in HIV-1 chronically infected naive patients with CD4 count <500 cells/mm(3). Regulatory T cells were identified as CD4(+)CD25(high)CD127(low) cells among CD4(+) lymphocytes. Effect of Treg percentage at inclusion on CD4 evolution overtime was analyzed using a mixed-effect Poisson regression for count data. Results. Fifty-eight patients were included (median CD4 = 293/mm(3), median Treg percentage = 6.1%). Percentage of Treg at baseline and CD4 nadir were independently related to the evolution of CD4 absolute value according to time: (1) at any given nadir CD4 count, 1% increase of initial Treg was associated with a 1.9% lower CD4 absolute value at month 24; (2) at any given Treg percentage at baseline, 10 cell/mm(3) increase of CD4 nadir was associated with a 2.4% increase of CD4 at month 24; and (3) both effects did not attenuate with time. The effect of Treg at baseline on CD4 evolution was as low as the CD4 nadir was high. Conclusions. Regulatory T-cell percentage at baseline is a strong independent prognostic factor of immune recovery, particularly among patients with low CD4 nadir.

Nontuberculous Mycobacteria: An Underestimated Cause of Bioprosthetic Valve Infective Endocarditis.

Background. Atypical mycobacteria, or nontuberculous mycobacteria (NTM), have been barely reported as infective endocarditis (IE) agents. Methods. From January 2010 to December 2013, cardiac valve samples sent to our laboratory as cases of blood culture-negative suspected IE were analyzed by 16S rDNA polymerase chain reaction (PCR). When positive for NTM, hsp PCR allowed species identification. Demographic, clinical, echocardiographic, histopathological, and Ziehl-Neelsen staining data were then collected. Results. Over the study period, 6 of 370 cardiac valves (belonging to 5 patients in 3 hospitals) were positive for Mycobacterium chelonae (n = 5) and Mycobacterium lentiflavum (n = 1) exclusively on bioprosthetic material. The 5 patients presented to the hospital for heart failure without fever 7.1-18.9 months (median 13.1 months) after biological prosthetic valve implantation. Echocardiography revealed paravalvular regurgitation due to prosthesis dehiscence in all patients. Histopathological examination of the explanted material revealed inflammatory infiltrates in all specimens, 3 of which were associated with giant cells. Gram staining and conventional cultures remained negative, whereas Ziehl-Neelsen staining showed acid-fast bacilli in all patients. Allergic etiology was ruled out by antiporcine immunoglobulin E dosages. These 5 cases occurred exclusively on porcine bioprosthetic material, revealing a statistically significant association between bioprosthetic valves and NTM IE (P < .001). Conclusions. The body of evidence confirmed the diagnosis of prosthetic IE. The statistically significant association between bioprosthetic valves and NTM IE encourages systematic Ziehl-Neelsen staining of explanted bioprosthetic valves in case of early bioprosthesis dysfunction, even without an obvious sign of IE. In addition, we strongly question the cardiac bioprosthesis conditioning process after animal sacrifice.

Hepatomegaly and fever at the time of neutrophil recovery revealing L-asparaginase toxicity in the treatment of acute lymphoblastic leukemia.

PATIENT: Male, 52 FINAL DIAGNOSIS: L-asparaginase associated steatohepatitis and pulmonary Pneumocystis Symptoms: Cholestasis • hepatomegaly MEDICATION: Corticosteroids • atovaquone • antioxidant therapy Clinical Procedure: Liver biopsy Specialty: Hematology • Infectious Disease • Hepatology. OBJECTIVE: Challenging differential diagnosis. BACKGROUND: L-asparaginase (L-aspa) is an important component of chemotherapy in acute lymphoblastic leukemia (ALL). Main adverse effects of L-aspa include allergic reactions, pancreatitis, thrombosis, and liver disturbances. L-aspa-associated steatohepatitis may be a life-threatening disorder but has very rarely been reported in the literature. CASE REPORT: ALL was diagnosed in a 52-year-old man with a history of cardiovascular disease and obesity. Chemotherapy combining daunorubicin, vincristine, cyclophosphamide, and L-aspa was initiated. At the time of neutrophil recovery, the patient developed hepatomegaly in the context of fever and cough. On day 25, after 6 injections of L-aspa, liver function tests showed elevated alkaline phosphatase and transaminases levels. Although pulmonary Pneumocystis was concomitantly diagnosed, biological hepatic disturbances were attributed to L-aspa-associated toxicity. A liver biopsy revealed severe diffuse micro- and macrovesicular steatosis affecting more than 50% of hepatocytes. Other causes of liver dysfunction were eliminated. L-aspa and other hepatotoxic treatments were stopped, and treatment with antioxidant therapy, atovaquone, and corticosteroids was initiated. The clinical outcome was rapidly favorable. CONCLUSIONS: This case illustrates the necessity of carefully monitoring liver function test results in patients receiving L-aspa. In case of major increase of hepatic enzymes, a hepatic biopsy should rapidly be performed to exclude differential diagnosis in patients with prolonged neutropenia. L-aspa should be stopped and further administration definitively avoided. In the present case, the early administration of systemic corticosteroids as treatment of the concomitant Pneumocystis with hypoxemia could have participated to the favorable clinical evolution.

Relationship between discordant response to HAART, Tregs, immune activation and low-level viraemia.

INTRODUCTION: The incomplete immune recovery upon effective long-term highly active antiretroviral therapy (HAART) has been associated with increased morbidity and mortality in HIV infected patients [1]. Immune cellular activation, Tregs or very low-level viraemia has been alternatively suspected, but never investigated simultaneously [2]. MATERIALS AND METHODS: We performed a cross-sectional study in 87 aviraemic patients (men=62, mean CD4+T cells=570/mm(3), mean duration of HAART=12 years). Patients with at least 500 CD4+ T cells /mm(3) were classified as complete immunological responders (cIR), whereas remaining patients were classified as inadequate immunological responder (iIR). Tregs were characterized based on CD4+CD25highFoxP3+phenotype using a one-step intracellular staining. Effector Tregs and terminal effectors Tregs were respectively defined as CD4+CD25+FoxP3+CD45RA-, and CD4+CD25+FoxP3+CD45RA-HLADR+phenotypes as recently described [3]. Activated T cells were identified using (i) elevated HLA-DR expression for CD4+T cells, and (ii) increased expressions of HLA-DR, or CD38, or both (HLADR+CD38+cells) for CD8+T cells. Very low-level viraemia was defined as detectable viraemia between 1 and 39 cp/mL. Univariate and multivariate analyses were performed to identify determinants of iIR. RESULTS: Thirty-nine patients were classified as iIR, and 48 as cIR. Patients from the iIR group were significantly older (55 vs 50 years, p=0.027), and had percentages of activated CD4+ T cells, Tregs, effector Tregs and terminal effector Tregs significantly higher (5.3 vs 4%, p=0.014; 9 vs 7.5%, p=0,022; 8 vs 6.3%, p=0.01 and 1.8 vs 1.3%, p=0,033 among CD4+T cells, respectively). Neither the percentage of activated CD8+T cell nor very low-level viraemia were found to be associated with iIR. In the multivariate analysis, nadir of CD4+T cell count and percentage of Tregs were the only two parameters independently associated with iIR (OR=2.339, p=0.001, and OR=0.803, p=0.041, respectively). CONCLUSIONS: We present here the largest study investigating simultaneously immune response to long-term HAART, immune activation of CD4+ and CD8+ T cells, Tregs percentages and very low-level viraemia. Our results highlight the importance of Tregs in CD4 homeostasis. This aspect should now be prospectively explored in a large cohort of patients.

Assessment of a novel flow cytometry technique of one-step intracellular staining: example of FOXP3 in clinical samples.

BACKGROUND: By measuring multiple parameters on a single-cell basis, flow cytometry is a potent tool to dissect the phenotypes and functions of cell subsets. However, because this technique may be time-consuming, particularly for intracellular staining, it could be problematic for its use in daily routine or in large cohorts. Recently, a novel reagent has been developed to perform intracellular staining in one step. The objective of our study was thus to assess this new method in comparison with the reference technique by focusing on FOXP3 staining in clinical samples. METHODS: Peripheral blood was collected from 15 HIV-1-infected patients, 5 critically ill patients, and 5 healthy volunteers and stained using the two different methods. Different subsets of FOXP3 positive cells were investigated by flow cytometry. RESULTS: When comparing results obtained with the two techniques, no statistical differences between the percentages of CD4+FOXP3+, CD4+CD25+FOXP3+, and CD4+CD25+CD127-FOXP3+ cells were observed. Besides, a strong correlation between percentages of CD4+FOXP3+CD25+CD127- lymphocytes measured with both techniques was found in patients (r: 0.843, P < 0.001, intra-class correlation coefficient: 0.820, P < 0.001). Importantly, flow cytometry stainings obtained with the one-step method were very robust with an excellent intra-assay precision, a better discriminative power and correct stability and reproducibility of the staining even after blood storage. CONCLUSIONS: With a strong correlation between the percentages of FOXP3+ Tregs when compared with the reference method, a better staining quality, a shorter realization time and no need of isotype control, this one step procedure may represent an important improvement for a daily routine use of intracellular staining.

CD4+CD25+CD127- assessment as a surrogate phenotype for FOXP3+ regulatory T cells in HIV-1 infected viremic and aviremic subjects.

BACKGROUND: Although likely pivotal, the role of regulatory T cells (Tregs) in HIV pathogenesis remains elusive. This can be partly explained by analytical issues regarding their phenotypic identification in clinical studies. Instead of intracellular FOXP3 staining, CD4+CD25+CD127- phenotype has been proposed as an alternative to identify Tregs in clinical samples. However, its use remains controversial in viremic patients. Therefore, the objective of the present study was to assess the correlation between frequencies of CD4+CD25+CD127- and CD4+CD25+FOXP3+ lymphocytes in viremic and matched aviremic HIV-infected patients. METHODS: Peripheral blood was collected from HIV-1 infected patients. Eleven viremic patients (Viral Load > 40 copies/mL) were matched (age, sex, CD4+ cell number) with 8 aviremic patients under highly active antiretroviral therapy (HAART). Fresh whole blood was immediately stained to analyze by flow cytometry the correlation between CD4+CD25+CD127- and the reference phenotype CD4+CD25+FOXP3+ lymphocytes in the same tube (four color staining CD4/CD25/CD127/FOXP3 for concomitant analysis of cell surface and intracellular markers). RESULTS: In both groups, no significant differences were observed when comparing CD4+CD25+CD127- and CD4+CD25+FOXP3+ cell frequencies. In line, a strong correlation between CD4+CD25+CD127- and CD4+CD25+FOXP3+ lymphocyte percentages was observed in the whole patient population (r: 0.948, P < 0.001) or each group separately: aviremic (r: 0.968, P < 0.001), viremic (r: 0.9, P < 0.001). Finally, we found that most CD4+FOXP3+ cells were indeed CD25+CD127-, both in viremic and aviremic groups (88.5% and 90.9%, respectively). CONCLUSIONS: We observed that CD4+CD25+CD127- phenotype is a good and easy-to-perform surrogate identification strategy for FOXP3+ regulatory T cells in both viremic and aviremic HIV-1-infected subjects. Thus, it represents a useful tool for monitoring Tregs in clinical research studies based on large cohorts of patients prospectively monitored, including HIV-infected subjects.

Fatal cumulative toxicities of HAART in a stable, AIDS-free, HIV-infected patient.

The authors describe the case of fatal cumulative toxicities in a 58-year-old AIDS-free, HIV-infected patient, who successively developed under highly active antiretroviral therapy (HAART): severe lipodystrophy, complicated osteoporosis, complicated non-cirrhotic portal hypertension of the liver (with ascites, portal thrombosis, oesophageal varices and protein-losing enteropathy) due to nodular regenerative hyperplasia. These cumulative HAART-related toxicities led to death, despite symptomatic treatment and the switch of antiretrovirals (especially didanosine) putatively involved in the process in these drug-mediated diseases. As morbidity and mortality in HIV infection continue to improve, it appears important to recognise such rare HAART-associated toxicities. This case illustrates the absolute necessity of investigating the long-term side effects of HAART in HIV infection, particularly in patients treated with first generation molecules. The switch strategy (switching old molecules to newer ones) is crucial in case of severe suspected toxicity and has to be discussed in asymptomatic patients largely exposed to first generation molecules, in order to prevent long-term toxicity.