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Here, we describe an invasive infection due to Trichosporon coremiiforme in an HIV positive patient with neutropenia. The strain was first erroneously identified as Trichosporon asahii by conventional methods, but correctly identified by mass spectrometry using matrix-assisted laser desorption/ionization time-of-flight technology (MALDI-TOF MS) and ribosomal DNA sequencing. The infection was successfully resolved after antifungal treatment with amphotericin B and fluconazole. This case report is a contribution to the study of T. coremiiforme infections and reinforces its relevance as a species capable of causing invasive human infection in immunocompromised patients and also contributes to the study of its susceptibility profile against antifungal drugs., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Histoplasmosis occurs in 5-10% of HIV-infected patients in endemic areas and evolves to severe and disseminated infection with mortality rates over 50% in some regions. This report presents epidemiological, clinical and outcome data from HIV-infected patients with histoplasmosis confirmed by culture and/or at necropsy who were admitted to a Brazilian teaching hospital. Data from 65 patients were obtained from their respective medical and necropsy records. From 2005 to 2018, 36 HIV-infected patients were diagnosed with histoplasmosis confirmed by culture. At admission, most of these patients presented disseminated fungal infection, whereas 15 (41.7%) were simultaneously diagnosed with both HIV infection and histoplasmosis. Fever, weight loss, hepatosplenomegaly, respiratory and digestive symptoms were present in 86.2%, 50%, 44.4% and 41.7% of the patients, respectively. At admission, 24 patients had low CD4 T-cell count and high viral load values. Among the 30 patients who received antifungals, 16 (53.3%) were cured, 13 (43.3%) died, and one was lost to follow-up. Six patients died prior to therapy. From 1990 to 2018, 63 necropsies of patients with Histoplasma capsulatum infection were performed. Of these patients, 29 (46.0%) were HIV-infected individuals, including 21 (72.4%) who presented disseminated histoplasmosis and 21 (72.4%) who were diagnosed with histoplasmosis at necropsy. The epidemiological, clinical and outcome profiles presented herein are similar to those described elsewhere and reinforce the difficulties that are still present in limited-resource settings where advanced immunodeficiency, combined with severe fungal infection and late patient admissions, is related to poor outcomes.

African histoplasmosis is the relatively unknown infection by Histoplasma capsulatum var. duboisii. It is endemic to Central and West Africa, generally involving the skin with potential for systemic dissemination, and has been described mainly in immunocompetent hosts. We present the case of a 30-year-old Bissau-Guinean man with HIV-2 infection known for 16 years, irregularly treated, admitted with two weeks of fever, diarrhoea and cutaneous lesions. Examination revealed multiple subcutaneous nodes, Molluscum contagiosum-like lesions, generalized lymphadenopathy and painful palpation of the left iliac fossa. Laboratory tests showed severe nonhaemolytic anaemia and CD4+ count of 9/mm3, with normal creatinine and hepatic enzymes. Chest roentgenogram was unremarkable and a research for Mycobacterium tuberculosis by GeneXpert® was negative. Nonetheless, given the lack of further diagnostic tools, a presumptive diagnosis of disseminated tuberculosis was made, and the patient was started on tuberculostatic and antiretroviral drugs. Despite initial improvement, a national shortage of antiretrovirals precluded further treatment, with worsening of the clinical picture, namely an increase in the number and dimensions of the skin lesions. An excisional biopsy of a subcutaneous nodule revealed Histoplasma capsulatum var. duboisii. Unfortunately, due to the unavailability of antifungals, the patient died one week later. To our best knowledge, this is the first confirmed case of an HIV infected patient with African histoplasmosis in Guinea-Bissau., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Objectives: Describe the epidemiology of immunocompromised HIV-infected pediatric (children and adolescents ≤ 19 years) and adults (> 19 years) with positive serum cryptococcal antigen lateral flow assay (CrAg-LFA) in KwaZulu-Natal., Design: Retrospective review of laboratory-based database and clinical charts., Methods: A review of the National Health Laboratory Services database of all serum CrAg-LFA performed in KwaZulu-Natal between June 2015 and December 2016 and comparison of the epidemiology of pediatric and adult patients was conducted. A reflex serum CrAg-LFA (IMMY CrAg-LFA) was performed on samples with CD4 counts < 100 cells/μL. Charts of all pediatric patients with a positive CrAg-LFA at Prince Mshiyeni Memorial Hospital were reviewed and 1-year outcome assessed., Results: A total of 22,741 laboratory records were retrieved, and 1140 records were removed because of duplicate entries (1074) and insufficient data (64). There was a statistically significant difference in the incidence of positive CrAg-LFA in pediatrics and adults, respectively [40 (3.5%) versus 1194 (5.8%), P = 0.001]. The incidence of positive CrAg-LFA in Ethekwini district was 59 and 56 cases per 100,000 persons in adolescents 10-14 years and 15-19 years, respectively. Six of the 8 patients with available treatment history were on antiretroviral treatment (ART) with immune failure at the time of CrAg-LFA testing., Conclusions: Severe immune suppression in adolescents on ART is a risk factor for cryptococcal antigenemia. A concerted effort to timeously manage ART failure in adolescents with appropriate changing of ART regimens is urgently warranted.

Introduction: Cryptococcal meningitis (CM) is the most common systemic fungal infection in patients with HIV infection. Rapid diagnosis and timely initiation of antifungal therapy are key to reducing mortality rate associated with CM. This study aims to evaluate the ability of four different diagnostic tests (Gram stain, India ink, and two types of commercial lateral flow assay [LFA]) to identify CM-positive patients and to compare the sensitivity and specificity of these tests., Methods: This was a prospective cross-sectional study on diagnostic tests accuracy conducted in Northern Malawi. The target population was HIV-infected adult patients presenting with features of meningitis. Four types of diagnostic tests were conducted: India ink, Gram stain, and two types of commercial lateral flow assay (LFA) (Immy, Inc., OK, USA and Dynamiker Biotechnology (Tianjin) Co., Ltd), Singapore). Culture was conducted as the reference standard., Results: A total of 265 samples were collected. The rate of positive CM detection ranged from 6.4% (using India ink) to 14.3% (using LFA). India ink exhibited the lowest sensitivity of 54.8% (95% confidence interval [CI]: 36.0%-72.7%), followed by Gram stain (61.3%; 95% CI: 42.2%-78.2%). The Dynamiker LFA exhibited the highest sensitivity of 100.0% (95% CI: 90.0%-100.0%) but a lower specificity (97.0%; 93.9%-98.8%) compared to the Immy LFA (98.3%; 95% CI: 95.7%-99.5%)., Conclusion: LFA diagnostic methods have the potential to double the detection rate of CM-positive patients in resource-limited countries such as Malawi. As such, LFAs should be considered to become the main diagnostic tests used for CM diagnostics in these countries. Our data indicate that LFAs may be the best method for diagnosing CM and exhibits the highest diagnostic accuracy as it has shown that it outperforms cell culture, the current gold standard., (© 2020 The College of Medicine and the Medical Association of Malawi.)

Background: The global annual estimate for cryptococcal disease-related deaths exceeds 180,000, with three fourth occurring in sub-Saharan Africa. The World Health Organization (WHO) recommends cryptococcal antigen (CrAg) screening in all HIV patients with CD4 count < 100/μl. As there is no previous published study on the burden and impact of cryptococcal disease in Sierra Leone, research is needed to inform public health policies. We aimed to establish the seroprevalence and mortality of cryptococcal disease in adults with advanced HIV attending an urban tertiary hospital in Sierra Leone., Methods: A prospective cohort study design was used to screen consecutive adult (18 years or older) HIV patients at Connaught Hospital in Freetown, Sierra Leone with CD4 count below 100 cells/mm 3 from January to April 2018. Participants received a blood CrAg lateral flow assay (IMMY, Oklahoma, USA). All participants with a positive serum CrAg had lumbar puncture and cerebrospinal fluid (CSF) CrAg assay, and those with cryptococcal diseases had fluconazole monotherapy with 8 weeks followed up. Data were entered into Excel and analysed in Stata version 13.0. Proportions, median and interquartile ranges were used to summarise the data. Fisher's exact test was used to compare categorical variables., Results: A total of 170 patients, with median age of 36 (IQR 30-43) and median CD4 count of 45 cells/mm 3 (IQR 23-63) were screened. At the time of enrolment, 54% were inpatients, 51% were newly diagnosed with HIV, and 56% were either ART-naïve or newly initiated (≤ 30 days). Eight participants had a positive blood CrAg, giving a prevalence of 4.7% (95% CI: 2.4-9.2%). Of those with a positive CrAg, CSF CrAg was positive in five (62.5%). Five (62.5%) CrAg-positive participants died within the first month, while the remaining three were alive and established on ART at 8 weeks., Conclusion: A substantial prevalence of cryptococcal antigenaemia and poor outcome of cryptococcal disease were demonstrated in our study. The high mortality suggests a need for the HIV programme to formulate and implement policies on screening and pre-emptive fluconazole therapy for all adults with advanced HIV in Sierra Leone, and advocate for affordable access to effective antifungal therapies.

Background: The aim of this study was to evaluate the dentists' knowledge and practice regarding HIV positive individuals' oral care in Rio de Janeiro State., Methods: Dentists from Rio de Janeiro State (n = 242) answered an electronic questionnaire on biosafety procedures, oral manifestations of AIDS, and knowledge of HIV infection. Collected information was stratified by gender, and data were analyzed using Chi-square and t tests., Results: From the 14 oral manifestations investigated, oral candidiasis, necrotizing ulcerative gingivitis, and hairy leucoplakia were more associated with HIV, with no differences between the responses from men and women. Above 85% of the participants would be concerned about becoming infected with HIV after a needle/ sharp object injury and more than 80% of them were willing to be tested for HIV. However, significantly more women (98.8%), compared to men (91.3%), said they knew that HIV/ AIDS patients can contaminate dental care professionals, p = 0.007. There was a significant difference in the answers for the questions: "Are there special dental clinics for treatment of HIV/AIDS patients in Brazil?" (p = 0.044), and "Do the negative HIV tests surely indicate that the persons are free of viruses?" (p = 0.005). Significant differences between men and women were also observed regarding use of disposable mask (p = 0.01), and cap (p < 0.0001)., Conclusion: Most dentists who participated in the study presented a good knowledge on the care of HIV/ AIDS individuals, including biosafety protocols and in terms of the oral manifestations commonly associated to AIDS.

Background: Disseminated Kaposi sarcoma (DKS) is present in patients with advanced HIV infection in whom co-infection with other opportunistic pathogens can occur. Bone marrow (BM) aspirate and biopsy comprise a robust diagnostic tool in patients with fever, cytopenias, and abnormal liver tests. However, the yield in patients with DKS has not been determined., Objective: The aim of this study was to evaluate the utility of BM aspirate and biopsy in patients with DKS., Methods: We included 40 male patients with a recent diagnosis of DKS. BM aspirate and biopsy was performed as part of the workup to rule out co-infections., Results: In four patients, Mycobacterium avium complex (MAC) was recovered from culture. In other four patients, intracellular yeasts were observed in the Grocott stain, diagnosed as Histoplasma. The yield of BM was calculated in 20%. Only 12 patients (30%) had fever and 11 (27.5%) had pancytopenia. Alkaline phosphatase (ALP) above normal values and C-reactive protein (CRP) were higher in patients with positive results for BM than in those with negative results (63% vs. 21.9%, and 3.0 vs. 1.2 mg/L; p = 0.03 in both comparisons). No differences were found when complete blood-count abnormalities were compared., Conclusion: We recommend performing a BM aspirate for stains, culture, and biopsy in all HIV patients with DKS, as this will permit the early diagnosis of co-infections and prevent further complications in those who receive chemotherapy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Purpose : To characterize the presenting features of cytomegalovirus (CMV) retinitis in HIV-positive patients in a developing country in the HAART era. Methods : Retrospective chart review of all patients with CMV retinitis seen at a tertiary-care referral center between January 2006 to June 2017. Demographic and clinical data were collected to study the presenting features and risk factors for blindness. Results : Fifty-five patients with treatment-naïve CMV retinitis were enrolled; 75% were males. CD4 counts were below 50 cells/µL in 51.1%. Bilateral presentation was seen in 61.5%. Half (50.6%) of the eyes were blind at first examination. Zone 1 involvement was present in 46% of the eyes. Retinal area involvement > 25% was the only factor associated significantly with higher incidence of blindness ( p  = 0.016). Conclusions : There was extensive and bilateral presentation of CMV retinitis due to delayed presentation. Screening for CMV retinitis, irrespective of CD4 counts, may help in developing nations.

Background & Aims: There have been calls to integrate HCV testing into existing services, including harm reduction and HIV prevention and treatment, but there are few empirical trials to date. We evaluated the impact of integrating HCV testing/education into integrated care centers (ICCs) delivering HIV services to people who inject drugs (PWID) across India, using a cluster-randomized trial., Methods: We compared ICCs with usual care in the PWID stratum (12 sites) of a 22-site cluster-randomized trial. In 6 sites, ICCs delivering HIV testing, harm reduction, other preventive services and linkage to HIV treatment were scaled from opioid agonist therapy centers and operated for 2 years. On-site rapid HCV antibody testing was integrated after 1 year. To assess impact, we conducted baseline and evaluation surveys using respondent-driven sampling (RDS) across the 12 sites (n = 11,993 recruited at baseline; n = 11,721 recruited at evaluation). The primary outcome was population-level self-reported HCV testing history., Results: At evaluation, HCV antibody prevalence ranged from 7.2-76.6%. Across 6 ICCs, 5,263 ICC clients underwent HCV testing, of whom 2,278 were newly diagnosed. At evaluation, PWID in ICC clusters were 4-fold more likely to report being tested for HCV than in usual care clusters, adjusting for baseline testing (adjusted prevalence ratio [aPR] 3.69; 95% CI 1.34-10.2). PWID in ICC clusters were also 7-fold more likely to be aware of their HCV status (aPR 7.11; 95% CI 1.14-44.3) and significantly more likely to initiate treatment (aPR 9.86; 95% CI 1.52-63.8)., Conclusions: We provide among the first empirical data supporting the integration of HCV testing into HIV/harm reduction services. To achieve elimination targets, programs will need to scale-up such venues to deliver comprehensive HCV services. CLINICALTRIALS., Gov Identifier: NCT01686750., Lay Summary: Delivering hepatitis C virus (HCV) testing to people who inject drugs (PWID) in places where they also have access to HIV prevention and treatment services is an effective way to improve uptake of HCV testing among communities of PWID. To achieve the World Health Organization's ambitious elimination targets, integrated programs will need to be scaled up to deliver comprehensive HCV services., (Copyright © 2019 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: Effective combination antiretroviral therapy (cART) has tremendously reduced HIV-associated morbidity, mortality and mother-to-child transmission. However, the benefits of cART are threatened by comorbidities, adverse drug reactions and virus resistance to existing treatment regimens. One of the most occurring comorbidities is cytomegalovirus (CMV) infection., Objectives: To investigate the effects of cART on the occurrence of CMV infection among pregnant women., Methods: Using a cross-sectional study design, 175 HIV-infected pregnant women were recruited, and data were obtained from their clinical records. Blood samples were collected for host DNA, CMV DNA and plasma efavirenz (EFV) measurement. CMV DNA was measured using real-time polymerase chain reaction (PCR). CYP2B6 c.516G&gt;T and CYP2B6 c.983T&gt;C single nucleotide polymorphisms were characterised using PCR/restriction fragment length polymorphism and TaqMan assays, respectively. Plasma EFV concentrations were determined using high-performance liquid chromatography., Results: There was an inverse association between plasma EFV concentration and CMV DNA. Participants with lower plasma EFV concentrations were significantly (p&lt;0.001) more likely to be CMV DNA positive than those with higher plasma concentrations. This result is also supported by the observation that carriers of CYP2B6 poor-metaboliser genotypes (CYP2B6 c.516T/T and CYP2B6 c.983T/C) were less likely to be positive for CMV DNA. Furthermore, poor metabolism as denoted by CYP2B6 c.516T/T and CYP2B6 c.983T/C genotypes was significantly associated with lower CMV viral load., Conclusions: HIV treatment disrupts the balance between host and co-infecting microbes. Reduced or subtherapeutic levels of antiretroviral drugs, which could be exacerbated by genetic polymorphisms in drug metabolism genes and non-adherence, predispose infected individuals to an increased risk of CMV infection in pregnancy.

Background: Cryptococcal prostatitis is a rare clinical disease and has never been reported in China., Case Presentation: We report on a male HIV-infected patient with pulmonary and prostate cryptococcosis that was misdiagnosed (as tuberculosis) and delayed diagnosed. Although the patients accepted anti-fungal treatment and anti-retroviral treatment finally, the physician's mistakes reflect the rarity of this condition in China., Conclusion: Cryptococcal prostatitis is a rare disease that unusually presents in immunodeficient patients. Physicians should have a heightened awareness of this particular infection in the immunodeficient population.

Background and Objectives: Pneumocystis pneumonia (PCP) is a common opportunistic infection in acquired immune deficiency syndrome (AIDS) patients that continues to result in a high mortality rate. To develop a better treatment strategy and improve PCP prognosis, a cohort study was conducted to evaluate the therapeutic potential of echinocandin treatment for AIDS patients with PCP (AIDS-PCP)., Methods: The AIDS-PCP patients were analyzed in our retrospective cohort study that were hospitalized in The First Affiliated Hospital of Zhejiang University during 2013-2018. The antifungal effects of echinocandins were evaluated in two subgroups that were classified by oxygenation as a proxy for the disease state: PaO 2 /FiO 2 > 200 mmHg and PaO 2 /FiO 2 ≤ 200 mmHg. Intergroup comparisons and survival curves were used to evaluate the effectiveness of the two AIDS-PCP treatment regimens., Results: During the follow-up, 182 AIDS-PCP patients were diagnosed and analyzed in the study. After excluding 55 patients with other superinfections and five patients that were treated with HAART, the remaining 122 patients were enrolled in the study. The group treated with echinocandins combined with trimethoprim-sulfamethoxazole (TMP-SMZ) and clindamycin exhibited a lower mortality rate (9.62%, 5/52) than did the group with TMP-SMZ and clindamycin treatment (20%, 14/70). For AIDS-PCP patients in the PaO 2 /FiO 2 > 200 mmHg subgroup, treatment with echinocandins combined with TMP-SMZ and clindamycin significantly reduced their mortality rate (4.44% (2/45) vs. 18.18% (10/55), P = 0.035)., Conclusion: The results of this study indicate that treatment with echinocandins in combination with the standard TMP-SMZ and clindamycin regimen can improve the prognosis and reduce the mortality rate in patients with mild to moderate AIDS-PCP disease., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2019 Mengyan Wang et al.)

Background: Toxoplasmosis is one of the most common comorbidities in HIV-positive patients with CD4+ T lymphocytes below 200 cells/μl. Early diagnosis and treatment of toxoplasmosis reduces the mortality rate in HIV-positive people. The aim of this study was to estimate the seroprevalence of Toxoplasma gondii infection in HIV-positive patients in northwest Iran using serological and molecular methods., Methods: This prospective cross-sectional study included 124 HIV-positive outpatients and was conducted from January to May 2016. Anti-T. gondii IgM and IgG antibodies were detected from sera samples by chemiluminescence, while buffy coat samples were analyzed by RT-PCR for DNA detection. Patients' socioepidemiological data were collected., Results: Using chemiluminescence, 47/124 samples (37.9%) were positive for anti-Toxoplasma IgG antibodies, 2/124 samples (1.62%) were positive for IgM antibodies while 2/124 samples (1.62%) contained both IgM and IgG. There were no IgM-positive or IgG-negative patients. RT-PCR revealed four (3.22%) positive samples. On the basis of the results, a statistically significant relationship was found between anti-Toxoplasma IgG antibody seropositivity and residence (p=0.012)., Conclusions: The study showed a relatively low seroprevalence of anti-T. gondii IgG and IgM antibodies in HIV-positive patients in northwest Iran, while the prevalence was much higher in other regions of Iran. However, regular screening for T. gondii antibodies and early initiation of therapy are very important to decrease the mortality rate in HIV-positive patients., (© The Author(s) 2019. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Most of the previous reports regarding the clinical features of Kaposi's sarcoma (KS) have been performed in Western and African countries. The clinical characteristics of KS have not been well defined in Han Chinese or Taiwanese patients. In this study, we analyzed the clinical features of KS patients in a Taiwanese medical center., Methods: Medical records from Kaohsiung Medical University Hospital over the past 20 years (1996-2016) were comprehensively reviewed., Results: There were 55 patients with KS (50 males and 5 females), including 37 patients (67%) with classic disease, 17 patients (31%) with AIDS-associated disease, and one patient (2%) with immunosuppressive medication-related disease. The average age was 58.7 years (range 20-87 years), and the average age was younger for AIDS patients (33.8 years) compared with non-AIDS patients (69.8 years). Among patients with classic KS, lesions were mostly localized to the lower extremities, whereas AIDS-associated KS patients were more likely to develop disseminated skin lesions, skin lesions on atypical sites (head and neck, trunk), and extracutaneous involvement (particularly oral cavity). The most common underlying diseases were diabetes mellitus (20% of patients) and hepatitis B (15% patients), and 38% of KS patients were smokers. Patients with AIDS-associated KS usually responded well to chemotherapy, whereas only 32% of patients with non-AIDS-associated KS showed complete response to radiotherapy., Conclusions: The findings of the current study will serve as important references for clinicians in the diagnosis of KS and may form the basis for the implementation of KS clinical practice guidelines in Taiwan., (© 2019 The International Society of Dermatology.)

Pneumocystis carinii pneumonia is a common opportunistic respiratory infection among children with human immunodeficiency virus and a weakened immune system. The primary infection in immunocompetent patients may be asymptomatic, whereas fever, shortness of breath, night sweats, nonproductive (dry) cough, pneumonia, progressive respiratory distress and apnea are cardinal symptoms of full-blown pneumocystis pneumonia. The diagnosis can be confirmed by histochemical staining of biological specimens or, recently, by polymerase chain reaction. International recommendations indicate that the drug of choice is the intravenously administered trimethoprim-sulfamethoxazole combination. Early diagnosis and appropriate treatment reduce the mortality of the disease. This article briefly highlights the epidemiology of Pneumocystis pneumonia, its diagnosis and therapeutic options in the pediatric population., (© 2019 Magdalena Zakrzewska, Renata Roszkowska, Mateusz Zakrzewski , Elżbieta Maciorkowska, published by Sciendo.)

We report the case of a 79-year-old patient with pancytopenia and blue-purple cutaneous lesions on his legs, arms and in the oral cavity. These lesions had been present for several months. Based on a positive HIV test result we made a presumptive diagnosis of cutaneous Kaposi sarcoma. Histological examination confirmed the diagnosis of AIDS-related Kaposi sarcoma.

Approximately 21 human cases of infection with Mycobacterium conceptionense have been reported. However, most cases were outside the United States, and optimal treatment remains uncertain. We report a case of M. conceptionense pneumonitis in a patient with HIV/AIDS in the United States. The patient was cured with azithromycin and doxycycline.

AIDS-related Kaposi sarcoma (KS) is a malignancy seen in patients with HIV/AIDS that results from unrestrained human herpesvirus 8 infection. It can have an atypical presentation and an aggressive clinical course in patients with uncontrolled HIV infection. We present an interesting case of AIDS-related KS with an atypical initial presentation with skin nodules and debilitating lymphoedema. Patient was successfully managed with supportive measures, antiretroviral therapy and systemic chemotherapy., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Talaromyces marneffei is a fungal opportunistic infection usually seen in immunocompromised patients from eastern countries. In the US when examining HIV-patients for suspected fungal infections, laboratory serological tests guide therapy until cultures are available. We present the case of a 35-year-old HIV patient originally from Thailand in which urine lab results were positive for Blastomyces and Histoplasma antigen, but biopsy showed T. marneffei. Concomitantly the patient presented with hyponatremia which was deemed to be from SIADH. We present the first case of a patient with T. marneffei cross reactivity with Blastomyces, Histoplasma and SIADH due to pulmonary disease., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Diagnosis of tuberculosis should be improved in children infected with HIV to reduce mortality. We developed prediction scores to guide antituberculosis treatment decision in HIV-infected children with suspected tuberculosis., Methods: HIV-infected children with suspected tuberculosis enrolled in Burkina Faso, Cambodia, Cameroon, and Vietnam (ANRS 12229 PAANTHER 01 Study), underwent clinical assessment, chest radiography, Quantiferon Gold In-Tube (QFT), abdominal ultrasonography, and sample collection for microbiology, including Xpert MTB/RIF (Xpert). We developed 4 tuberculosis diagnostic models using logistic regression: (1) all predictors included, (2) QFT excluded, (3) ultrasonography excluded, and (4) QFT and ultrasonography excluded. We internally validated the models using resampling. We built a score on the basis of the model with the best area under the receiver operating characteristic curve and parsimony., Results: A total of 438 children were enrolled in the study; 251 (57.3%) had tuberculosis, including 55 (12.6%) with culture- or Xpert-confirmed tuberculosis. The final 4 models included Xpert, fever lasting >2 weeks, unremitting cough, hemoptysis and weight loss in the past 4 weeks, contact with a patient with smear-positive tuberculosis, tachycardia, miliary tuberculosis, alveolar opacities, and lymph nodes on the chest radiograph, together with abdominal lymph nodes on the ultrasound and QFT results. The areas under the receiver operating characteristic curves were 0.866, 0.861, 0.850, and 0.846, for models 1, 2, 3, and 4, respectively. The score developed on model 2 had a sensitivity of 88.6% and a specificity of 61.2% for a tuberculosis diagnosis., Conclusions: Our score had a good diagnostic performance. Used in an algorithm, it should enable prompt treatment decision in children with suspected tuberculosis and a high mortality risk, thus contributing to significant public health benefits., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2019 by the American Academy of Pediatrics.)

Great progress has been made in caring for persons with human immunodeficiency virus. However, a significant proportion of individuals still present to care with advanced disease and a low CD4 count. Careful considerations for selection of antiretroviral therapy as well as close monitoring for opportunistic infections and immune reconstitution inflammatory syndrome are vitally important in providing care for such individuals., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Extrapulmonary tuberculosis (EPTB) is difficult to confirm bacteriologically and requires specific diagnostic capacities. Diagnosis can be especially challenging in under-resourced settings. We studied diagnostic modalities and clinical outcomes of EPTB compared to pulmonary tuberculosis (PTB) among HIV-positive adults in antiretroviral therapy (ART) programmes in low- and middle-income countries (LMIC)., Methods: We collected data from HIV-positive TB patients (≥16 years) in 22 ART programmes participating in the International Epidemiology Databases to Evaluate AIDS (IeDEA) consortium in sub-Saharan Africa, Asia-Pacific, and Caribbean, Central and South America regions between 2012 and 2014. We categorized TB as PTB or EPTB (EPTB included mixed PTB/EPTB). We used multivariable logistic regression to assess associations with clinical outcomes., Results and Discussion: We analysed 2695 HIV-positive TB patients. Median age was 36 years (interquartile range (IQR) 30 to 43), 1102 were female (41%), and the median CD4 count at TB treatment start was 114 cells/μL (IQR 40 to 248). Overall, 1930 had PTB (72%), and 765 EPTB (28%). Among EPTB patients, the most frequently involved sites were the lymph nodes (24%), pleura (15%), abdomen (11%) and meninges (6%). The majority of PTB (1123 of 1930, 58%) and EPTB (582 of 765, 76%) patients were diagnosed based on clinical criteria. Bacteriological confirmation (using positive smear microscopy, culture, Xpert MTB/RIF, or other nucleic acid amplification tests result) was obtained in 897 of 1557 PTB (52%) and 183 of 438 EPTB (42%) patients. EPTB was not associated with higher mortality compared to PTB (adjusted odd ratio (aOR) 1.0, 95% CI 0.8 to 1.3), but TB meningitis was (aOR 1.9, 95% CI 1.0 to 3.1). Bacteriological confirmation was associated with reduced mortality among PTB patients (aOR 0.7, 95% CI 0.6 to 0.8) and EPTB patients (aOR 0.3 95% CI 0.1 to 0.8) compared to TB patients with a negative test result., Conclusions: Diagnosis of EPTB and PTB at ART programmes in LMIC was mainly based on clinical criteria. Greater availability and usage of TB diagnostic tests would improve the diagnosis and clinical outcomes of both EPTB and PTB., (© 2019 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Background: Universal antiretroviral therapy (ART) with annual population testing and a multidisease, patient-centered strategy could reduce new human immunodeficiency virus (HIV) infections and improve community health., Methods: We randomly assigned 32 rural communities in Uganda and Kenya to baseline HIV and multidisease testing and national guideline-restricted ART (control group) or to baseline testing plus annual testing, eligibility for universal ART, and patient-centered care (intervention group). The primary end point was the cumulative incidence of HIV infection at 3 years. Secondary end points included viral suppression, death, tuberculosis, hypertension control, and the change in the annual incidence of HIV infection (which was evaluated in the intervention group only)., Results: A total of 150,395 persons were included in the analyses. Population-level viral suppression among 15,399 HIV-infected persons was 42% at baseline and was higher in the intervention group than in the control group at 3 years (79% vs. 68%; relative prevalence, 1.15; 95% confidence interval [CI], 1.11 to 1.20). The annual incidence of HIV infection in the intervention group decreased by 32% over 3 years (from 0.43 to 0.31 cases per 100 person-years; relative rate, 0.68; 95% CI, 0.56 to 0.84). However, the 3-year cumulative incidence (704 incident HIV infections) did not differ significantly between the intervention group and the control group (0.77% and 0.81%, respectively; relative risk, 0.95; 95% CI, 0.77 to 1.17). Among HIV-infected persons, the risk of death by year 3 was 3% in the intervention group and 4% in the control group (0.99 vs. 1.29 deaths per 100 person-years; relative risk, 0.77; 95% CI, 0.64 to 0.93). The risk of HIV-associated tuberculosis or death by year 3 among HIV-infected persons was 4% in the intervention group and 5% in the control group (1.19 vs. 1.50 events per 100 person-years; relative risk, 0.79; 95% CI, 0.67 to 0.94). At 3 years, 47% of adults with hypertension in the intervention group and 37% in the control group had hypertension control (relative prevalence, 1.26; 95% CI, 1.15 to 1.39)., Conclusions: Universal HIV treatment did not result in a significantly lower incidence of HIV infection than standard care, probably owing to the availability of comprehensive baseline HIV testing and the rapid expansion of ART eligibility in the control group. (Funded by the National Institutes of Health and others; SEARCH ClinicalTrials.gov number, NCT01864603.)., (Copyright © 2019 Massachusetts Medical Society.)

Competing Interests: Competing interests: None declared.

Background: In high-burden settings, case fatality rates are reported to be between 11% and 32% in hospitalized patients with HIV-associated tuberculosis, yet the underlying causes of mortality remain poorly characterized. Understanding causes of mortality could inform the development of novel management strategies to improve survival. We aimed to assess clinical and microbiologic determinants of mortality and to characterize the pathophysiological processes underlying death by evaluating host soluble inflammatory mediators and determined the relationship between these mediators and death as well as biomarkers of disseminated tuberculosis., Methods and Findings: Adult patients with HIV hospitalized with a new diagnosis of HIV-associated tuberculosis were enrolled in Cape Town between 2014 and 2016. Detailed tuberculosis diagnostic testing was performed. Biomarkers of tuberculosis dissemination and host soluble inflammatory mediators at baseline were assessed. Of 682 enrolled participants, 576 with tuberculosis (487/576, 84.5% microbiologically confirmed) were included in analyses. The median age was 37 years (IQR = 31-43), 51.2% were female, and the patients had advanced HIV with a median cluster of differentiation 4 (CD4) count of 58 cells/L (IQR = 21-120) and a median HIV viral load of 5.1 log10 copies/mL (IQR = 3.3-5.7). Antituberculosis therapy was initiated in 566/576 (98.3%) and 487/576 (84.5%) started therapy within 48 hours of enrolment. Twelve-week mortality was 124/576 (21.5%), with 46/124 (37.1%) deaths occurring within 7 days of enrolment. Clinical and microbiologic determinants of mortality included disseminated tuberculosis (positive urine lipoarabinomannan [LAM], urine Xpert MTB/RIF, or tuberculosis blood culture in 79.6% of deaths versus 60.7% of survivors, p = 0.001), sepsis syndrome (high lactate in 50.8% of deaths versus 28.9% of survivors, p < 0.001), and rifampicin-resistant tuberculosis (16.9% of deaths versus 7.2% of survivors, p = 0.002). Using non-supervised two-way hierarchical cluster and principal components analyses, we describe an immune profile dominated by mediators of the innate immune system and chemotactic signaling (interleukin-1 receptor antagonist [IL-1Ra], IL-6, IL-8, macrophage inflammatory protein-1 beta [MIP-1β]/C-C motif chemokine ligand 4 [CCL4], interferon gamma-induced protein-10 [IP-10]/C-X-C motif chemokine ligand 10 [CXCL10], MIP-1 alpha [MIP-1α]/CCL3), which segregated participants who died from those who survived. This immune profile was associated with mortality in a Cox proportional hazards model (adjusted hazard ratio [aHR] = 2.2, 95%CI = 1.9-2.7, p < 0.001) and with detection of biomarkers of disseminated tuberculosis. Clinicians attributing causes of death identified tuberculosis as a cause or one of the major causes of death in 89.5% of cases. We did not perform longitudinal sampling and did not have autopsy-confirmed causes of death., Conclusions: In this study, we did not identify a major contribution from coinfections to these deaths. Disseminated tuberculosis, sepsis syndrome, and rifampicin resistance were associated with mortality. An immune profile dominated by mediators of the innate immune system and chemotactic signaling was associated with both tuberculosis dissemination and mortality. These findings provide pathophysiologic insights into underlying causes of mortality and could be used to inform the development of novel treatment strategies and to develop methods to risk stratify patients to appropriately target novel interventions. Causal relationships cannot be established from this study., Competing Interests: The authors have declared that no competing interests exist.

Introduction: TB has seen resurgence associated with HIV. Tuberculosis can affect any ocular tissue. The association of HIV with TB is supposed to increase the incidence and plethora of ocular manifestations in tuberculosis., Objectives: To study the various ocular manifestations seen in tuberculosis patients with associated HIV infection., Material and Methods: This hospital based, cross sectional descriptive study was conducted in Tribhuvan University, Teaching Hospital, Maharajgunj, Nepal and Geta Eye Hospital, Kailali from 2010 to 2015. Diagnosed cases of pulmonary and extra pulmonary tuberculosis with HIV co infection were evaluated for ocular manifestations after excluding other opportunistic infections., Results: Of 70 cases eligible for the study, extra pulmonary tuberculosis was seen in60% of the cases. 5 patients (7.1 %) had ocular manifestations. CD4 counts were <50/mm3 in 3 cases. Ocular involvement was seen in the form of choroidal granulomas, papillitis, cranial nerve palsy, retinal vasculitis and central serous chorioretinopathy., Conclusion: This study demonstrated that ocular involvement is a frequent finding in cases with tuberculosis and HIV. Ocular findings are more common in cases with lesser CD4 counts. As ocular tuberculosis can be visually devastating, we recommend regular ocular evaluation of all patients with HIV and systemic tuberculosis., (© NEPjOPH.)

Background: Cryptococcosis is a generally systemic and potentially lethal fungal infection. Although HIV infection is a predisposing condition, especially if the CD 4+ lymphocyte count is less than 100cells/mm 3 , other forms of immunosuppression may be associated with this opportunistic fungal condition, such as prolonged steroid therapy or solid organ transplantation. Pulmonary presentation must be included in the differential diagnosis of pneumonia or pulmonary neoplasia in the immunosuppressed patient., Case Report: We report a case of pulmonary cryptococcosis in a non-diagnosed HIV patient. In a 44 year-old male suffering from dyspnea and chest pain the image of a pulmonary nodule was observed in a radiological finding. In the histopathological study, intracellular structures suggestive of fungal conidia, and morphologically compatible with Cryptococcus, were observed. HIV serology and cryptococcal antigen detection in serum were requested, given the possibility of cryptococcosis. Cryptococcus neoformans var. grubii was isolated from the culture of the pulmonary biopsy. The patient was finally diagnosed with pulmonary cryptococcosis and HIV-1 infection. With a proper antifungal treatment the patient evolved satisfactorily., Conclusions: The best strategy to avoid opportunistic infections such as cryptococcosis in HIV-infected patients consists of an early diagnosis and a highly active antiretroviral treatment. In our case, the diagnosis of a pulmonary infection by C. neoformans var. grubii allowed a late diagnosis of HIV-1 infection., (Copyright © 2019 Asociación Española de Micología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: We defined the cut-off values of the antigenemia and cytomegalovirus (CMV) DNA tests in HIV/AIDS patients to identify CMV disease., Methods: A total of 97 samples from 68 patients with and without CMV disease were analyzed by viral DNA detection and antigenemia assay., Results: Qualitative and quantitative results significantly differed between assays. The cut-off values for the antigenemia and qPCR assays were 1.5 positive cells/200,000 leukocytes and 3.715 log/mL, respectively., Conclusions: Antigenemia and qPCR are suitable for monitoring CMV disease in HIV patients, however, the threshold values should be determined within the centers where the patients are monitored.

Competing Interests: Competing interests: None declared.

Background: The urine lipoarabinomannan (LAM) lateral flow assay is a point-of-care test to diagnose HIV-associated tuberculosis (TB). We assessed the performance of urine LAM in HIV-positive patients presenting to the emergency center and evaluated the interobserver agreement between emergency center physicians and laboratory technologists., Setting: A cross-sectional diagnostic study was performed at the emergency center of a district hospital in a high HIV-prevalence community in South Africa., Methods: Consecutive HIV-positive adults presenting with ≥1 WHO TB symptom were enrolled over a 16-month period. A urine LAM test was performed at point-of-care by an emergency physician and interpreted independently by 2 physicians. A second test was performed in the laboratory and interpreted independently by 2 laboratory technologists. The reference standard was a positive TB culture or Xpert MTB/RIF test on sputum or appropriate extrapulmonary samples. We compared diagnostic accuracy and reproducibility of urine LAM between point-of-care readers and laboratory readers., Results: One thousand three hundred eighty-eight samples (median, 3 samples/participant) were sent for TB microbiology tests in 411 participants; 170 had confirmed TB (41.4%). Point-of-care and laboratory-performed urine LAM had similar sensitivity (41.8% vs 42.0%, P = 1.0) and specificity (90.5% vs 87.5%, P = 0.23). Moderate agreement was found between point-of-care and laboratory testing (κ = 0.62), but there was strong agreement between point-of-care readers (κ = 0.95) and between laboratory readers (κ = 0.94). Positive percent agreement between point-of-care and laboratory readers was 68% and negative percent agreement 92%., Conclusion: There is no diagnostic accuracy advantage in laboratory-performed versus point-of-care-performed urine LAM tests in emergency care centers in high-burden settings.

Psoriasis is a prevalent systemic immune-mediated disease with cutaneous manifestations. In HIV-infected patients, psoriasis may have a higher incidence, present atypical and more exuberant clinical features, and is frequently recalcitrant to treatment. Despite this aggravated severity, treatment options for psoriasis in HIV-infected individuals remain limited due to the risk of fatal immunosuppression associated with both classical immunosuppressants and new biological drugs. Notwithstanding, drug therapy in psoriasis has been undergoing major advances for the last few years, with novel drugs approved, which could significantly add to the management of HIV-infected patients. It is therefore our aim to present a review of the available literature to highlight the updated evidence on psoriasis in HIV-infected individuals, particularly in regards to its epidemiology, proposed pathophysiology, clinical presentation, currently available therapeutic options, and future perspectives.

Kaposi's sarcoma-associated herpesvirus (KSHV) causes both AIDS-related Kaposi's sarcoma (KS) and classic KS, but their clinical presentations are different, and respective mechanisms remain to be elucidated. The KSHV K1 gene is reportedly involved in tumorigenesis through the immunoreceptor tyrosine-based activation motif (ITAM). Since we found the sequence variations in the K1 gene of KSHV isolated from AIDS-related KS and classic KS, we hypothesized that the transformation activity of the K1 gene contributes to the different clinical presentations. To evaluate our hypothesis, we compared the transformation activities of the K1 gene between AIDS-related KS and classic KS. We also analyzed ITAM activities and the downstream AKT and NF-κB. We found that the transformation activity of AIDS-related K1 was greater than that of classic K1, and that AIDS-related K1 induced higher ITAM activity than classic K1, causing more potent Akt and NF-κB activities. K1 downregulation by siRNA in AIDS-related K1 expressing cells induced a loss of transformation properties and decreased both Akt and NF-κB activities, suggesting a correlation between the transformation activity of K1 and ITAM signaling. Our study indicates that the increased transformation activity of AIDS-related K1 is associated with its clinical aggressiveness, whereas the weak transformation activity of classic type K1 is associated with a mild clinical presentation and spontaneous regression. The mechanism of spontaneous regression of classic KS may provide new therapeutic strategy to cancer.

Background: The prevalence of and mortality from HIV-associated tuberculosis (HIV/TB) in hospital inpatients in Africa remains unacceptably high. Currently, there is a lack of tools to identify those at high risk of early mortality who may benefit from adjunctive interventions. We therefore aimed to develop and validate a simple clinical risk score to predict mortality in high-burden, low-resource settings., Methods and Findings: A cohort of HIV-positive adults with laboratory-confirmed TB from the STAMP TB screening trial (Malawi and South Africa) was used to derive a clinical risk score using multivariable predictive modelling, considering factors at hospital admission (including urine lipoarabinomannan [LAM] detection) thought to be associated with 2-month mortality. Performance was evaluated internally and then externally validated using independent cohorts from 2 other studies (LAM-RCT and a Médecins Sans Frontières [MSF] cohort) from South Africa, Zambia, Zimbabwe, Tanzania, and Kenya. The derivation cohort included 315 patients enrolled from October 2015 and September 2017. Their median age was 36 years (IQR 30-43), 45.4% were female, median CD4 cell count at admission was 76 cells/μl (IQR 23-206), and 80.2% (210/262) of those who knew they were HIV-positive at hospital admission were taking antiretroviral therapy (ART). Two-month mortality was 30% (94/315), and mortality was associated with the following factors included in the score: age 55 years or older, male sex, being ART experienced, having severe anaemia (haemoglobin < 80 g/l), being unable to walk unaided, and having a positive urinary Determine TB LAM Ag test (Alere). The score identified patients with a 46.4% (95% CI 37.8%-55.2%) mortality risk in the high-risk group compared to 12.5% (95% CI 5.7%-25.4%) in the low-risk group (p < 0.001). The odds ratio (OR) for mortality was 6.1 (95% CI 2.4-15.2) in high-risk patients compared to low-risk patients (p < 0.001). Discrimination (c-statistic 0.70, 95% CI 0.63-0.76) and calibration (Hosmer-Lemeshow statistic, p = 0.78) were good in the derivation cohort, and similar in the external validation cohort (complete cases n = 372, c-statistic 0.68 [95% CI 0.61-0.74]). The validation cohort included 644 patients between January 2013 and August 2015. Median age was 36 years, 48.9% were female, and median CD4 count at admission was 61 (IQR 21-145). OR for mortality was 5.3 (95% CI 2.2-9.5) for high compared to low-risk patients (complete cases n = 372, p < 0.001). The score also predicted patients at higher risk of death both pre- and post-discharge. A simplified score (any 3 or more of the predictors) performed equally well. The main limitations of the scores were their imperfect accuracy, the need for access to urine LAM testing, modest study size, and not measuring all potential predictors of mortality (e.g., tuberculosis drug resistance)., Conclusions: This risk score is capable of identifying patients who could benefit from enhanced clinical care, follow-up, and/or adjunctive interventions, although further prospective validation studies are necessary. Given the scale of HIV/TB morbidity and mortality in African hospitals, better prognostic tools along with interventions could contribute towards global targets to reduce tuberculosis mortality., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: KD has obtained speaker fees at industry-sponsored symposia and non-financial support from Alere in the form of kits and test strips, outside the submitted work. No other authors declare competing interests.