Accuracy of saliva and nasopharyngeal sampling for detection of SARS-CoV-2 in community screening: a multicentric cohort study.

Nasopharyngeal sampling for nucleic acid amplification testing (NAAT) is the standard diagnostic test of coronavirus disease 2019. Our objectives were to assess, in real-life conditions, the diagnostic accuracy of a nasopharyngeal point-of-care antigen (Ag) test and of saliva NAAT for detection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in ambulatory care. This was a prospective cohort study from 19 October through 18 December 2020 in two community COVID-19 screening centers in Paris, France. Two nasopharyngeal swabs and one saliva sample were simultaneously collected. Diagnostic accuracies of nasopharyngeal Ag testing and of three saliva NAAT methods were assessed as compared to nasopharyngeal NAAT. A total of 1452 ambulatory children and adults were included. Overall, 129/1443 (9%) participants tested positive on nasopharyngeal NAAT (102/564 [18%] in symptomatic and 27/879 [3%] in asymptomatic participants). Sensitivity was 94%, 23%, 96%, and 94% for the three different protocols of saliva NAAT and for the nasopharyngeal Ag test, respectively. Estimates of specificity were above 95% for all methods. Diagnostic accuracy was similar in symptomatic and asymptomatic individuals. Diagnostic accuracy of nasopharyngeal Ag testing and of saliva NAAT is similar to that of nasopharyngeal NAAT, subject to compliance with specific protocols for saliva. Registration number: NCT04578509.

Episomal HPV16 responsible for aggressive and deadly metastatic anal squamous cell carcinoma evidenced in peripheral blood.

Archival tissue samples collected longitudinally from a patient who died from HPV16-induced high-grade anal intraepithelial squamous cell carcinoma with vertebral HPV16-positive metastasis were retrospectively analyzed by the Capture-HPV method (Capt-HPV) followed by Next-Generation Sequencing (NGS). Full length nucleotide sequences of the same HPV16 were identified from the initial and second anal biopsy samples, from plasma sample and from vertebral metastasis biopsy. Remarkably, HPV was episomal in each sample. The HPV genome sequence was closest to the HPV16 Qv18158E variant subtype (A1 lineage) exhibiting base substitutions and deletions in 7 and 2 HPV loci, respectively. In conclusion, the powerful Capt-HPV followed by NGS allows evidencing the detailed cartography of tumoral and circulating HPV DNA, giving rise to a unique and unexpected episomal virus molecular status in a context of aggressive carcinoma, underlying the importance of HPV status and its association with clinical features for further prospective studies.

Missed opportunities for HIV testing in patients newly diagnosed with HIV in Morocco.

BACKGROUND: In Morocco, of the estimated 29,000 people living with HIV in 2011, only 20% were aware of their HIV status. More than half of diagnoses were at the AIDS stage. We assumed that people who were unaware of their infection had contacts with the healthcare system for HIV indicators that might prompt the healthcare provider to offer a test. The aim was to assess missed opportunities for HIV testing in patients newly diagnosed with HIV who accessed care in Morocco. METHODS: A cross-sectional study was conducted in 2012-2013 in six Moroccan HIV centers. Participants were aged ≥18, and had sought care within 6 months after their HIV diagnosis. A standardized questionnaire administered during a face-to-face interview collected the patient's characteristics at HIV diagnosis, HIV testing and medical history. Contacts with care and the occurrence of clinical conditions were assessed during the 3 years prior to HIV diagnosis. Over this period, we assessed whether healthcare providers had offered HIV testing to patients with HIV-related clinical or behavioral conditions. RESULTS: We enrolled 650 newly HIV-diagnosed patients (median age: 35, women: 55%, heterosexuals: 81%, diagnosed with AIDS or CD4 < 200 cells/mm3: 63%). During the 3 years prior to the HIV diagnosis, 71% (n = 463) of participants had ≥1 contact with the healthcare system. Of 323 people with HIV-related clinical conditions, 22% did not seek care for them and 9% sought care and were offered an HIV test by a healthcare provider. The remaining 69% were not offered a test and were considered as missed opportunities for HIV testing. Of men who have sex with men, 83% did not address their sexual behavior with their healthcare provider, 11% were not offered HIV testing, while 6% were offered HIV testing after reporting their sexual behavior to their provider. CONCLUSIONS: Among people who actually sought care during the period of probable infection, many opportunities for HIV testing, based on at-risk behaviors or clinical signs, were missed. This highlights the need to improve the recognition of HIV clinical indicators by physicians, further expand community-based HIV testing by lay providers, and implement self-testing to increase accessibility and privacy.

Risk of Severe Bacterial Infection in People Living Human Immunodeficiency Virus Infection in the Combined Antiretroviral Therapy Era.

BACKGROUND: Severe bacterial infections are the first cause of morbidity in people with human immunodeficiency virus (PWH). We aimed to assess their incidence and to analyze their determinants. METHODS: We studied human immunodeficiency virus (HIV)-1-infected individuals aged at least 15 years and prospectively followed between 2006 and 2015 in the French Hospital Database on HIV. The Andersen and Gill model was used to calculate the adjusted hazard ratios (HRs), focusing on heavy alcohol use and neutrophil function-altering comorbidities. RESULTS: Of 25 795 participants, 1414 developed 1883 severe bacterial infections. Between 2006 and 2009 and 2013 and 2015, the incidence fell from 13.2 (95% confidence interval [CI], 12.3-14.1) to 7.1 (95% CI, 6.3-7.8) per 1000 person-years. Heavy alcohol use was associated with an increased risk of severe bacterial infection (HR = 1.3, 95% CI = 1.1-1.7 for 40-80 g/day and HR = 1.6, 95% CI = 1.2-2.1 for >80 g/day), as were diabetes, chronic kidney disease, and end-stage liver disease (HR = 1.2, 95% CI = 1.0-1.4 when 1 comorbidity; HR = 2.3, 95% CI = 1.6-3.4 when more than 1 comorbidity), and nonacquired immune deficiency syndrome-defining malignancy (HR = 2.0; 95% CI, 1.6-2.4). CONCLUSIONS: Heavy alcohol use was associated with an increased risk of severe bacterial infection, as were neutrophil function-altering comorbidities. Controlled-drinking approaches should be promoted and comorbidity management should be strengthened in PWH.

Factors associated with anal cancer screening uptake in men who have sex with men living with HIV: a cross-sectional study.

Most western countries have guidelines on anal cancer screening for men who have sex with men (MSM) living with HIV. However, adherence to these guidelines has been studied poorly. This cross-sectional study reports anal cancer screening uptake and identifies the factors associated with a previous screening in MSM living with HIV in a Paris Hospital (France). A total of 410 outpatients completed a self-administered questionnaire on anal cancer screening. The median age was 50 years and the median time from HIV diagnosis was 14.2 years. Overall, 82.2% of patients were aware of anal cancer screening and, of these, 56.7% had already undergone a screening test. The absence of history of screening (43.3%) was most often explained by lack of time (31.3%) or information (28.2%). Among patients familiar with the anal screening procedure, those older than 50 years (adjusted odds ratio=2.4, 95% confidence interval=1.3-4.7, P=0.007) and informed by healthcare providers (adjusted odds ratio=8.2, 95% confidence interval=2.5-32.0, P=0.001) were more likely to have already been screened. To date, adherence to anal cancer screening in MSM living with HIV appears to be inadequate to enable diagnosis of cancer at its early stages. Encouraging physicians to inform MSM living with HIV about anal cancer screening, irrespective of their age, could be an effective strategy to improve anal cancer screening uptake.

Influence of geographic origin on AIDS and serious non-AIDS morbidity/mortality during cART among heterosexual HIV-infected men and women in France.

BACKGROUND: The influence of geographic origin on the risk of severe illness and death on cART has not been explored in European countries. METHOD: We studied antiretroviral-naïve heterosexual HIV-1-infected individuals enrolled in the FHDH-ANRS CO4 cohort in France who started cART between 2006 and 2011. Individuals originating from France (French natives), sub-Saharan Africa (SSA) and non-French West-Indies (NFW) were studied until 2012. Crude and adjusted rate ratios (aRR) of severe morbid events/deaths (AIDS-related and non-AIDS-related) were calculated using Poisson regression models stratified by sex, comparing each group of migrants to French natives. RESULTS: Among 2334 eligible men, 1379 (59.1%) originated from France, 838 (35.9%) from SSA and 117 (5.0%) from NFW. SSA male migrants had a higher aRR for non-AIDS infections, particularly bacterial infections (aRR 1.56 (95% CI 1.07-2.29), p = 0.0477), than French natives. Among 2596 eligible women, 1347 (51.9%) originated from France, 1131 (43.6%) from SSA, and 118 (4.5%) from NFW. SSA and NFW female migrants had a higher aRR for non-AIDS infections, particularly non-bacterial infections (respectively, 2.04 (1.18-3.53) and 7.87 (2.54-24.4), p = 0.0010), than French natives. We observed no other significant differences related to geographic origin as concerns the aRRs for AIDS-related infections or malignancies, or for other non-AIDS events/deaths such as cardiovascular disease, neurological/psychiatric disorders, non-AIDS malignancies and iatrogenic disorders, in either gender. CONCLUSION: Heterosexual migrants from SSA or NFW living in France have a higher risk of non-AIDS-defining infections than their French native counterparts. Special efforts are needed to prevent infectious diseases among HIV-infected migrants.

Comparison of anal cancer screening strategies including standard anoscopy, anal cytology, and HPV genotyping in HIV-positive men who have sex with men.

BACKGROUND: There is no consensus on screening strategy of high-grade intraepithelial neoplasia (HGAIN). Guidelines range from clinical examination with digital anorectal examination followed by standard anoscopy (SA), to anal cytology (Pap)+/- HPV genotyping. We compared screening strategy yields based on Pap, SA, and HPV-16 genotyping alone or in combination in HIV-MSM. METHODS: Pap, SA, and HPV-16 genotyping were performed in all HIV-MSM attending a first anal cancer screening consultation in Paris, France. High-resolution anoscopy, the gold standard to detect HGAIN, was performed in the case of HPV-16 positivity or abnormal cytology. Yield was defined as the number of patients with HGAIN relative to the total number of patients screened. RESULTS: On 212 patients, the complete strategy (SA + Pap + HPV genotyping) yield (12.7%) was significantly higher than that of SA (3.3%, p < 0.001) and HPV-16 alone (6.6%, p < 0.05). Although none of the other strategies were significantly different from the complete strategy, Pap + HPV-16 and Pap + SA had closer yields (about 11%), with OR = 0.83 (95% CI [0.44;1.57]) and 0.87 (95% CI [0.46;1.64]), respectively. CONCLUSIONS: Pap combined with HPV-16 genotyping or SA tended towards higher yields compared to Pap alone, and closer to that of the complete strategy.

Cohort Profile: French hospital database on HIV (FHDH-ANRS CO4).

The French Hospital Database on HIV (FHDH) is a hospital-based multicentre open cohort with inclusions ongoing since 1989. The research objectives focus mainly on mid- and long-term clinical outcomes and therapeutic strategies, as well as severe AIDS and non-AIDS morbidities, and public health issues relative to HIV infection. FHDH also serves to describe HIV-infected patients receiving hospital care in France. FHDH includes data on more than 120,000 HIV-infected patients from 70 French general or university hospitals distributed throughout France. Patients are eligible for inclusion if they are infected by HIV-1 or HIV-2 and give their written informed consent. Standardized variables are collected at each outpatient visit or hospital admission during which a new clinical manifestation is diagnosed, a new treatment is prescribed or a change in biological markers is noted, and/or at least every 6 months. Since its inception, variables collected in FHDH include demographic characteristics, HIV-related biological markers, the date and type of AIDS and non AIDS-defining events, antiretroviral treatments and the date and causes of death, as reported in the medical records. Since 2005, data have also been collected on: co-infection with hepatitis B or C virus; alcohol and tobacco use; and non HIV-related biomarkers. Anyone can submit a research project by completing a standardized form available on the FHDH website (http://www.ccde.fr/_fold/fl-1385734776-429.pdf) or from the corresponding author, describing the context and objectives of the study. All projects are reviewed by the scientific committee.

Prevalence of opportunistic intestinal parasitic infections among HIV-infected patients with low CD4 cells counts in France in the combination antiretroviral therapy era.

BACKGROUND: The use of combination antiretroviral therapy (cART) has dramatically reduced the prevalence of opportunistic infections, however data on the prevalence of intestinal parasitic infections in HIV-infected patients with low CD4 cell counts in the cART era are scarce. METHODS: We performed a prospective cohort study among HIV-infected patients with CD4 cell counts <100/mm(3) seen at a university hospital in Paris. Medical records were reviewed and stool samples were obtained for macroscopic examination and detection of parasites including cryptosporidia and microsporidia, whether or not the patient had diarrhea. Stool cultures were performed for patients with diarrhea. Factors associated with the detection of parasites were then identified. RESULTS: Stools samples from 143 consecutive patients were analyzed. Patients were mostly men (76%), and the median patient age was 41 years. The median CD4 cell count was 32/mm(3), and 59% were receiving cART. Diarrhea was present in 85 patients (59%), 19 of whom (22%) had intestinal parasites detected in stools. Three patients with diarrhea were diagnosed with Salmonella typhimurium, Campylobacter coli, and Clostridium difficile infections. Among the 58 patients without diarrhea, parasitic intestinal pathogens were still identified in six (10%). The overall prevalence of intestinal parasites was 17%, with cryptosporidia (n=8), microsporidia (n=6), and Giardia duodenalis (n=5) being the most frequent pathogens. Patients with intestinal parasites had diarrhea more often (76% vs. 56%, p=0.025) and were more often at US Centers for Disease Control and Prevention (CDC) clinical stage C (84% vs. 69%, p=0.024) than patients without parasites. CONCLUSIONS: The prevalence of intestinal parasitic infections remains significant in HIV-infected patients with low CD4 counts in the cART era. A systematic search for parasitic pathogens including microsporidia, cryptosporidia, and G. duodenalis should be performed even in the absence of diarrhea.

AIDS-related Kaposi's sarcoma can occur during peginterferon-α and ribavirin therapy for chronic hepatitis C infection.

INTRODUCTION: Before the arrival of highly active antiretroviral therapy (HAART), interferon α has been used successfully to treat AIDS-related Kaposi's sarcoma (KS). Peginterferon-α (pegIFN-α) may still be used successfully in refractory KS. CASE: Peginterferon-α and ribavirin (RBV) were initiated to treat hepatitis C virus (HCV) infection in an HIV-infected patient with high CD4 counts having discontinued antiretroviral therapy (ART). He developed disseminated KS 6 months after HCV treatment began. Beginning of ART, discontinuation of pegIFN/RBV, and 2 cycles of doxorubicine were necessary to treat KS. DISCUSSION: Despite its activity on KS, thanks to its antiviral and antiangiogenic properties, PegIFN was unable to prevent the occurrence of severe KS. The absence of ART, despite high CD4 counts, and interferon-induced lymphopenia probably triggered the occurrence of KS in this patient.

Severe acute renal failure in an HIV-infected patient after only 2 weeks of tenofovir-based antiretroviral therapy.

We report a 46-year-old man who has sex with men (MSM) patient, of Scottish descent, who had no history of arterial hypertension, diabetes, or illicit drug use, was hepatitis C virus (HCV) negative but underwent right nephrectomy for urothelial tumor in 2006. Before starting antiretroviral therapy, he had a CD4 cell count of 316/mm(3) and plasma HIV RNA level was 1,020,537 copies per milliliter. He developed acute renal failure only 2 weeks after introduction of tenofovir-based antiretroviral therapy and then required 3 months of hemodialysis. After the end of hemodialysis, antiviral therapy was resumed with abacavir (300 mg×2/day), lamivudine (300 mg every day), and lopinavir/ritonavir (400/100 mg twice daily). Renal biopsy revealed severe and diffuse toxic acute tubular necrosis Two years after tenofovir discontinuation, the patient's renal function remained subnormal. Although severe renal toxicity due to tenofovir is rare, patients receiving tenofovir must be monitored closely for renal dysfunction especially during the first weeks of tenofovir therapy.

Breakthrough disseminated Aspergillus ustus infection in allogeneic hematopoietic stem cell transplant recipients receiving voriconazole or caspofungin prophylaxis.

Aspergillus ustus is an uncommon clinical species which is poorly susceptible to antifungals. We report two cases of A. ustus infections that occurred in allogeneic stem cell transplant recipients while they were receiving either voriconazole or caspofungin. Prolonged use of these new antifungal agents may increase the risk of the emergence of resistant organisms.

Successful treatment of pulmonary mucormycosis in an allogenic bone-marrow transplant recipient with combined medical and surgical therapy.

Mucormycosis is a rare, but severe, complication in allogenic bone-marrow recipients with a mortality rate of about 80%. Moreover, its incidence appears to have increased within the last decade. We report a case of pulmonary and nasal mucormycosis in a 55-y-old patient, which occurred 1 y after BMT. Treatment combining 4 months of amphotericin B, early surgical resection of infected tissue and discontinuation of immunosuppressive treatment allowed the cure of this mould infection.