The screening and management of sleep disturbances in people living with HIV: Delphi consensus.

Sleep disturbances in people living with HIV (PLHIV) are frequent but their management remains insufficient. In the absence of specific recommendations, a DELPHI consensus research project was conducted in France to establish best practice. A multidisciplinary Steering Committee (STC) undertook a literature review and used it with clinical expertise to create statements that were voted on. Two profiles of healthcare professionals with significant experience in monitoring PLHIV were selected for the voting: physicians and nurses/psychologists. Votes were collected electronically, independently, and anonymously. The STC created 27 statements covering six areas: Screening of sleep disturbances, Investigation, First-line management, Referral to a specialist, Antiretroviral treatment (ARV), and Prevention. Two rounds of votes included 42 physicians and 32 nurses/psychologists. Consensus was reached for 24 out of 27 statements (89%) including: to assess quantity and quality of sleep among PLHIV at least annually, ideally using a common methodology within the medical department; to consider the temporary addition of a hypnotic treatment in cases of acute insomnia not improved by the rules of sleep hygiene, with full awareness of potential drug-drug interactions and risk of dependence; to correct ferritinaemia if <100 ng/mL before referral to a specialist when restless legs syndrome is suspected; to consider changing the time of ARV administration or an ARV switch within the same class when sleep disturbances are caused by an ARV. This DELPHI Consensus provides best practice for screening and managing sleep disturbances in PLHIV and optimising their quality of life.

Successful Terbinafine Treatment for Cutaneous Phaeohyphomycosis Caused by Trematosphaeria grisea in a Heart Transplanted Man: Case Report and Literature Review.

Phaeohyphomycosis is a chronic infectious disease caused by dematiaceous fungi. It is characterized by the presence of pigmented septate mycelia within tissues. In the case of superficial infection, the lesion(s) chronically evolve(s) toward painless pseudo-tumor(s) of the soft parts. We report herein the original case of a heart transplanted man who exhibited phaeohyphomycosis of the left hand, with no mention of travels in endemic areas. Trematosphaeria grisea was identified as the causative agent, which is quite innovative since this species has been rather described in mycetoma. The antifungal treatment initially based on isavuconazole alone was not sufficient to cure the patient. In contrast, its association with local terbinafine ointment allowed total clinical improvement. This finding is unusual as diagnosis of phaeohyphomycosis caused by T. grisea is uncommon in nontropical countries, and as the outcome appeared successful by the means of add-on therapeutic strategy with terbinafine.

Acute Tibial osteomyelitis caused by intraosseous access during initial resuscitation: a case report and literature review.

BACKGROUND: Intra-osseous (IO) access is recommended in cases of pre-hospital emergency or resuscitation when intravascular (IV) route is difficult or impossible. Despite recent improvement in IO devices and increasing indications, it remains rarely used in practice. Various complications have been reported but are uncommon. CASE PRESENTATION: We report a case of massive acute tibial osteomyelitis in an adult male three months after an IO catheter insertion for emergency drug infusion. We review the literature on association between IO access and acute osteomyelitis in children and adults. CONCLUSIONS: Emergency-care givers and radiologists should be informed about this infrequent complication in order to make early diagnosis and initiate adequate antibiotic therapy.

Pneumocystis jirovecii pneumonia in HIV-negative patients: a prospective study with focus on immunosuppressive drugs and markers of immune impairment.

Pneumocystis jirovecii pneumonia (PCP) is emerging in HIV-negative patients, for whom the prognosis is significantly worse than in HIV-infected patients and risk factors are poorly characterized. We performed an observational, multi-centre, prospective study of 56 consecutive cases of documented PCP in HIV-negative patients, and found that: (1) the main underlying conditions were haematological malignancies (43%), solid tumours (25%), inflammatory diseases (20%), and solid organ transplantation (7%); (2) most patients (80%) had received prolonged corticosteroids, with a mean daily dose of 47.3 ± 32.8 mg equivalent prednisone when PCP was diagnosed, and a mean cumulative dose of 5807 ± 5048 mg over the last 12 months; and (3) the median CD4 cell count was 0.12 × 109/l (range 0.0-1.42), with a median CD4/CD8 ratio of 1.32 (0.0-6.4). These findings may be used to better target PCP prophylaxis according to the level of risk and contribute to decrease the burden of PCP in HIV-negative patients.

Reappraising Cladophialophora bantiana phaeohyphomycosis in France: retrospective nation-based study.

BACKGROUND: Cladophialophora bantiana is one of the most virulent phaeohyphomycetes, typically causes non-angiogenic single (or sometimes multiple) cystic brain lesions, and has resulted in a mortality rate of up to 70%. Most C bantiana cases are described either in a series of isolated reports or in very small cohorts. The aim of this retrospective nation-based study was to share the data on C bantiana phaeohyphomycosis cases reported in France and French overseas territories over the past two decades to improve understanding of this disease. METHODS: Patients with C bantiana infection were processed through the active surveillance programme of invasive fungal infections launched by the National Reference Center for Mycoses and Antifungals, Institut Pasteur (Paris, France), and the French Surveillance Network of Invasive Fungal Infections, which involved 29 hospitals from mainland France and overseas French territories. Only proven and probable cases of infection, according to the revised and updated consensus definitions from the European Organization for Research and Treatment of Cancer and Mycoses Study Group, were included in the study. Patients were diagnosed or confirmed, or both, using a polyphasic approach at the Institut Pasteur between 2002 and 2022. Patients were separated into two groups: those with CNS involvement and those with no CNS involvement. The primary outcome was the survival rate. FINDINGS: A total of 23 patients with a C bantiana invasive infection were included during the study period (Jan 1, 2002, to Dec 31, 2022). The median age was 56 years in the CNS involvement group and 65 years in the non-CNS involvement group. Until 2021, the annual number of cases varied between zero and two, with six cases observed in 2022, the warmest year recorded in France since 1900. CNS involvement was observed in 15 (65%) patients, including three disseminated cases; skin and soft tissue involvement in seven (30%) patients and an isolated lung infection in one case. Diabetes was observed in five patients, and any immunodepression factor was observed in 14 (61%) of 23 patients. When considering only patients with CNS involvement, 9-month survival appeared higher in patients who underwent exeresis or large drainage (three [75%] of four patients vs three [27%] of 11 patients; p=0·24) and significantly higher in those treated for 2 or more weeks with triple antifungal therapy (liposomal amphotericin B plus posaconazole and flucytosine; seven [78%] of nine patients vs one [17%] of six patients; p=0·040). Two patients were treated with excision surgery alone (one patient with success, and the other patient lost to follow-up). INTERPRETATION: This study shows that the clinical presentations and underlying medical conditions of C bantiana infections are more diverse than previously described. It also emphasises a significant difference in mortality rate between those with and without CNS involvement. The prognosis improved when surgery was performed and triple antifungal therapy was administered. Such rare and devastating invasive fungal infections should be managed by a multidisciplinary team. FUNDING: Santé Publique France.

[Tuberculosis -HIV, a common and sensitive care in connection with a case of pleural tuberculosis revealing AIDS]. / Co-infection tuberculose-VIH, une association fréquente et une prise en charge délicate : à propos d'un cas de tuberculose pleurale révélatrice de sida.

Tuberculosis is the most common disease inaugural of AIDS in France and HIV serology should be offered routinely when a tuberculosis case is diagnosed. Similarly, tuberculosis should also be sought before starting antiretroviral treatment. The case of pleural tuberculosis revealing AIDS presented here illustrates the difficulties of management of this co-infection due to polychemotherapy used to treat each of these pathologies causing drug interactions requiring dose adjustments and changes in treatment protocol and an increase in side effects. This is especially true when combining rifampicin and protease inhibitors and non-nucleoside reverse transcriptase inhibitors. On the other hand, resistance of Mycobacterium tuberculosis is possible in these patients coinfected by HIV particularly among migrants and in the case history of tuberculosis treatment.

Revisiting HBV resistance to entecavir with a phenotypic approach.

Treatment adaptation after hepatitis B virus (HBV) treatment failure relies on genotypic resistance testing. However, the results of such tests are not always consistent with treatment response. These discrepancies may be due to differences in resistance levels between isolates with the same genotypic resistance testing profiles. We explored this hypothesis by investigating six cases of entecavir treatment failure with an integrative strategy combining genotypic and phenotypic resistance testing, medical record review and therapeutic drug monitoring. Among isolates with genotypic reduced susceptibility to entecavir, one displayed a higher level of resistance to entecavir (mean fold change in entecavir IC50 of 1 508 ± 531 vs. 318 ± 53, p = 0.008). This isolate harbored a substitution (rt250L) at a position reported to be associated with resistance (rt250V). Reversion to wild-type amino acid at this position partially restored susceptibility to entecavir, confirming that the rt250L mutation was responsible for the high level of resistance to entecavir. This is the first description of entecavir treatment failure associated with selection of the rt250L mutation without other entecavir resistance mutations. One isolate with genotypic resistance to entecavir, harboring the rt173L mutation, displayed a lower level of resistance than the other, harboring the rt202G mutation (mean fold change of 323 ± 124 vs. 6 036 ± 2 100, p = 0.20). These results suggest that isolates harboring the rt250L mutations should be considered resistant to entecavir, whereas isolates harboring the rt173L mutations should be considered to display reduced susceptibility to entecavir. An integrative approach to antiviral drug resistance in HBV would provide a more accurate assessment of entecavir treatment failures and help to improve the accuracy of genotypic testing algorithms.

Characteristics and clinical outcomes after treatment of a national cohort of PCR-positive Lyme arthritis.

OBJECTIVES: To describe the clinical and microbiological characteristics and outcomes after antibiotic treatment of a national cohort of patients with Lyme arthritis confirmed by PCR testing on synovial fluid and by serology, when available. METHODS: Using the French National Reference Center for Borrelia database, patients with a positive PCR on synovial fluid for Borrelia were identified. Patient clinical and biological characteristics were reviewed from patient records. Long-term outcomes after treatment were studied through a questionnaire and with follow-up data. RESULTS: Among 357 synovial fluid testing by PCR between 2010 and 2016, 37 (10.4%) were positive for Borrelia. Patients' median age was 36 years (range 6-78) with 61% of men and 28% patients under 18. The presentation was monoarticular in 92% and the knee was involved in 97%. Contrary to the Borrelia species repartition in European ticks, B. burgdorferi sensu stricto was the most prevalent species found in synovial fluid (54%) followed by B. azfelii (29%) and B. garinii (17%). Antibiotic treatments were mainly composed of doxycycline (n = 24), ceftriaxone (n = 10) and amoxicillin (n = 6), for a median duration of 4 weeks (range 3-12). Despite a properly conducted treatment, 34% of patients (n = 12) developed persistent synovitis for at least 2 months (median duration 3 months, range 2-16). Among those, 3 developed systemic inflammatory oligo- or polyarthritis in previously unaffected joints with no signs of persistent infection (repeated PCR testing negative), which mandated Disease-Modifying Antirheumatic Drugs (DMARD) introduction, leading to remission. CONCLUSION: In France and contrary to ticks ecology, Lyme arthritis is mainly caused by B. burgdorferi sensu stricto. Despite proper antibiotic therapy, roughly one third of patients may present persistent inflammatory synovitis and a small proportion may develop systemic arthritis. In such cases, complete remission can be reached using DMARD.

Unusual pharmacokinetics of intravitreal and systemic voriconazole in a patient with Scedosporium apiospermum endophthalmitis.

In this paper, we report a case of a post-traumatic Scedosporium endophthalmitis treated with a posterior vitrectomy, followed by intravitreal injections and systemic voriconazole. This is the second documented case of S. apiospermum endophthalmitis treated with voriconazole and the first case with intravitreal injections of voriconazole. A 29-year-old man developed endophthalmitis after being struck in the left eye by a chip from a swimming pool pump. Despite 3 weeks of prophylactic antibiotherapy, his visual acuity remained only for the perception of light and vitreous inflammation increased. A creamy-white fungal mass grew at the inferior peripheral retina and pars plana. The fungus was identified as S. apiospermum. Oral voriconazole, at 200 mg twice-daily, did not bring the infection under control, considering the low plasma and intravitreal concentrations. Before steady-state plasma voriconazole concentrations reached an efficacy level greater than minimum inhibitory concentration of Scedosporium, intravitreal injections of 64 ug/0.1 mL of voriconazole were initiated twice-weekly for 3 weeks. Administration of higher intravenous voriconazole doses (6 mg/kg b.i.d.) for 6 weeks was needed to achieve an antifungal effect without systemic dissemination.

[HPV vaccine and cervical cancer prevention in general practice. Survey conducted among general practitioners in the French departments of Eure-et-Loir and Cher]. / Vaccination anti-HPV dans le cadre de la prévention du cancer du col de l'utérus en médecine générale. Enquête réalisée auprès des médecins généralistes d'Eure-et-Loir et du Cher.

General practitioners are the first line to promote the human papillomavirus vaccine in teenagers and young female adults. The goal of this study is: to describe the perception, in France, of this vaccine by the general practitioners in the first 6 months after the publication of national recommendations and reimbursement of this vaccine by the Social security; to know the daily practice of the cervical cancer prevention. These questions were asked through a questionnaire sent to 545 general practitioners s in the Eure-et-Loir and Cher departments. We got 255 answers (46%); 73% have already use this vaccine, at least once, and 64% are ready to promote this immunization in girls over the age of 14.70% think the national recommendations can be applied without any negative impact on the cervical cancer screening by the cervical-smear because human papillomavirus vaccine do not eliminate the need of cervical cancer screening; 81% are motivated to justify this immunization in their patients even if 10% spontaneously mention the problem of the hepatitis B immunization in France as a limitation to implementation of a new vaccine. Although these results are encouraging, cervical cancer screening should be intensified and general practitioners, patients and their parents should get better information.

Probing the compartmentalization of HIV-1 in the central nervous system through its neutralization properties.

Compartmentalization of HIV-1 has been observed in the cerebrospinal fluid (CSF) of patients at different clinical stages. Considering the low permeability of the blood-brain barrier, we wondered if a reduced selective pressure by neutralizing antibodies (NAb) in the central nervous system (CNS) could favor the evolution of NAb-sensitive viruses in this compartment. Single genome amplification (SGA) was used to sequence full-length HIV-1 envelope variants (453 sequences) from paired CSF and blood plasma samples in 9 subjects infected by HIV variants of various clades and suffering from diverse neurologic disorders. Dynamics of viral evolution were evaluated with a bayesian coalescent approach for individuals with longitudinal samples. Pseudotyped viruses expressing envelope glycoproteins variants representative of the quasi-species present in each compartment were generated, and their sensitivity to autologous neutralization, broadly neutralizing antibodies (bNAbs) and entry inhibitors was assessed. Significant compartmentalization of HIV populations between blood and CSF were detected in 5 out of 9 subjects. Some of the previously described genetic determinants for compartmentalization in the CNS were observed regardless of the HIV-1 clade. There was no difference of sensitivity to autologous neutralization between blood- and CSF-variants, even for subjects with compartmentalization, suggesting that selective pressure by autologous NAb is not the main driver of HIV evolution in the CNS. However, we observed major differences of sensitivity to sCD4 or to at least one bNAb targeting either the N160-V1V2 site, the N332-V3 site or the CD4bs, between blood- and CSF-variants in all cases. In particular, HIV-1 variants present in the CSF were more resistant to bNAbs than their blood counterpart in some cases. Considering the possible migration from CSF to blood, the CNS could be a reservoir of bNAb resistant viruses, an observation that should be considered for immunotherapeutic approaches.

Cerebral aspergillosis in the critically ill: two cases of successful medical treatment.

OBJECTIVE: Invasive aspergillosis is associated with a poor prognosis, especially in critically ill patients with cerebral involvement. We present two cases of cerebral invasive aspergillosis successfully treated in the intensive care unit with combination antifungal therapies and without surgery. CASE PRESENTATION: The first patient was a 49-year-old man with rheumatoid arthritis who received corticosteroid and cyclophosphamide treatment and developed pulmonary and cerebral invasive aspergillosis. After failure of voriconazole the patient had a successful outcome with voriconazole and liposomal amphotericin B therapy. The patient returned home after an 8-month hospital stay. The second patient was a 54-year-old woman with pulmonary neoplasia and corticosteroid treatment who developed pulmonary and cerebral invasive aspergillosis. After failure of voriconazole and liposomal amphotericin B therapy the patient had a favorable outcome with liposomal amphotericin B and caspofungin therapy. The patient died 10 months after initial diagnosis of cardiac tamponade unrelated to fungal infection. DISCUSSIONS: These cases illustrate the improving prognosis of invasive aspergillosis due to the availability of new treatments, especially in cases of cerebral involvement. It also demonstrates that the outcome of critically ill patients requiring mechanical ventilation for invasive aspergillosis can be favorable. The treatment of patients with invasive cerebral aspergillosis in the intensive care setting should be encouraged.

Pregnancies after transjugular intrahepatic portosystemic shunt for noncirrhotic portal hypertension.

With the growing role of transjugular intrahepatic portosystemic shunt (TIPS) in the management of portal hypertension complications, a number of women of childbearing age are now being treated with TIPS. However, if pregnancy is unusual in patients with cirrhosis, it can occur in the case of noncirrhotic portal hypertension. To our knowledge, there are no data on pregnancy safety after TIPS insertion. We report the first case of a patient with noncirrhotic portal hypertension treated by TIPS who had two successful pregnancies. She presented with HIV-associated obliterative portopathy with recurrent variceal bleeding treated by TIPS. Pregnancies occurred later and progressed normally without maternal or fetal morbidity. There was no effect on TIPS patency, but only a moderate increase in the flow velocity in the portal vein, the stent, and the hepatic artery. Thus, TIPS does not seem to impair progression of pregnancy.

Unusual multiple large abscesses of the liver: interest of the radiological features and the real-time PCR to distinguish between bacterial and amebic etiologies.

We report a rare case of amebiasis generating 19 large liver abscesses. Such a quantity of abscesses is rare, especially when occurring in a young casual traveler without any immunodeficiency disorders. A possible co-infection was excluded. By contrast, the amebic etiology was confirmed by means of serology and real-time PCR.

Decreased specificity of an assay for recent infection in HIV-1-infected patients on highly active antiretroviral treatment: implications for incidence estimates.

The aim of this study was to estimate the rate of misclassification in treated HIV patients who initiated treatment at the chronic stage of HIV infection using an enzyme immunoassay (EIA) that discriminates between recent infection (RI; within 6 months) and established infection. The performance of EIA-RI was evaluated in 96 HIV-1 chronically infected patients on highly active antiretroviral therapy (HAART) with an undetectable viral load (VL) for at least 3 years. Demographic data, HIV-1 viral load, CD4(+) T-cell count, viral subtype, and treatment duration were collected. The subset of misclassified patients was further analyzed using samples collected annually. The impact on incidence estimates was evaluated by simulation. The specificity in treated patients was significantly lower (70.8 to 77.1%) than that observed in untreated patients (93.3 to 99.3%, P < 0.001). Patients falsely classified as recently infected had been treated for a longer period and had longer-term viral suppression than those correctly classified. The loss of specificity of the test due to treatment may have a dramatic impact on the accuracy of the incidence estimates, with a major impact when HIV prevalence is high. The cross-sectional studies intended to derive HIV incidence must collect information on treatment or, alternatively, should include detection of antiretroviral drugs in blood specimens to rule out treated patients from the calculations.

Literature review and case histories of Histoplasma capsulatum var. duboisii infections in HIV-infected patients.

African histoplasmosis caused by Histoplasma capsulatum var. duboisii is an invasive fungal infection endemic in central and west Africa. Most of its ecology and pathogenesis remain unknown. H. capsulatum var. capsulatum is an AIDS-defining opportunistic infection in HIV-infected patients who are living in or have traveled to histoplasmosis-endemic areas. In contrast, reports concerning African histoplasmosis during HIV infection are rare, although both pathogens coexist in those regions. We report 3 cases of imported African histoplasmosis diagnosed in France in HIV-infected patients and a literature review on similar cases.