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Background: Visceral Leishmaniasis (VL) is the most severe and fatal disease if left untreated. In people living with HIV/AIDS (PLHA), VL is considered an emerging opportunistic infection. The aim of this manuscript was to report a first case in Tunisia of a concomitant presentation of visceral and oral leishmaniasis in a patient LHA. A systematic review of the literature was performed according to PRISMA guidelines, as well., Case Presentation: The patient, a 43-year-old heterosexual man, treated for HIV/AIDS was referred for macrocheilitis of the upper and lower lips. A noticeable nodular and painless swelling extending to the cheeks' mucosa was noted. The patient's poor oral hygiene was evident due to the presence of multiple dental caries. Histological analysis of the biopsied lower lip sample revealed the presence of numerous Leishmania amastigotes. The diagnosis of VL was clinically confirmed by the presence of a mild splenomegaly and pancytopenia and biologically by the identification of the parasite using PCR Lei and the species L. infantum involved using RFLP-PCR and culture. The treatment consisted of an intravenous administration of liposomal Amphotericin B (Ambisome®, 40 mg/kg/weight) for a period of 6 weeks. A favorable outcome was noted after one year with the resolution of clinical symptoms and a negative Leishmania blood PCR test. After 2 years, the patient remained asymptomatic but showed a positive Leishmania blood PCR test. Dolutegravir® was introduced in the patient's ART regimen., Conclusions: To the best of our knowledge, this is the first case report in Tunisia of atypical VL diagnosed through an uncommon oral location in an HIV/AIDS co-infected patient . Since VL is a severe and potentially fatal disease, it is essential for dentists to perform a thorough clinical examination and adopt a multidisciplinary approach in order to ensure an early diagnosis and an effective treatment outcome., (© 2024. The Author(s).)

Pneumocystis jirovecii pneumonia (PJP) is one of the leading opportunistic infections seen in people living with HIV. Bilateral infiltrations characterize PJP and miliary involvement is very rare. In this article, we report a 32-year-old person living with HIV who was followed up with a diagnosis of miliary PJP. Our patient was admitted to the hospital with complaints of cough, sputum, and weight loss. Initially, miliary tuberculosis was considered due to the presence of miliary involvement on chest radiography, but the diagnosis was made with P. jirovecii PCR positivity. This article aims to report a case of miliary PJP, a rare clinical form of PJP., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Competing Interests: Competing interests:: None declared.

Seronegative human immunodeficiency virus (HIV) infection, where an HIV-specific antibody response is lacking even in chronic or late-stage HIV infections, is extremely rare. Here, we report the case of a 50-year-old Japanese man presenting with Pneumocystis pneumonia who did not produce antibodies against HIV-1 until the initiation of antiretroviral therapy (ART). Fourth-generation antigen-antibody testing temporarily reverted from weakly positive to negative soon after initiating ART, likely due to a reduction in viral load (assessed by p24 antigen levels). His HIV-1 antibody titers remained low or indeterminate even after four years of ART. A literature review suggested that the absence of HIV-1-specific antibody production may be associated with unimpeded HIV replication and rapid CD4 + T cell decline. Seronegative HIV infection can lead to deferred diagnosis and treatment, thereby increasing the risk of transmitting the virus to others or developing opportunistic illnesses. It is important to combine multiple tests for diagnosis, depending on the medical condition. Further studies are required to investigate the host factors involved in the production of HIV-1-specific antibodies., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

While tuberculosis (TB) is an ancient disease, its global prevalence and concomitant human immunodeficiency virus (HIV)-1 infection have hampered efforts at effectively controlling TB in children in many countries where these 2 pandemics coexist. This review briefly discusses the current status of TB prevention strategies including preventative regimens designed to prevent the progression of latent TB infection to active disease, current recommendations regarding treatment of TB disease, and the problematic nature of diagnosing TB in children living with HIV. Promising recent data regarding novel diagnostic techniques that rely upon detecting Mycobacterium tuberculosis molecular components in blood will be reviewed., Competing Interests: Disclosure The author has nothing to disclose. Nanopin Biotechnologies: Research funding., (Copyright © 2024 Elsevier Inc. All rights reserved.)

A male in his 30s who was recently diagnosed with HIV arrived at the emergency department exhibiting an altered mental state and acute respiratory distress. Initial laboratory tests revealed a high anion gap metabolic acidosis, elevated liver enzyme levels and bicytopenia. A CT scan identified a miliary pattern. Bronchoscopy with bronchoalveolar lavage displayed epithelial and inflammatory cells. However, subsequent tests ruled out the presence of fungi, Pneumocystis organisms, malignancies, granulomas and viral inclusions. Broad-spectrum antibiotics with emphasis on Mycobacterium tuberculosis and antifungal treatments were administered. The regimen was adjusted after a positive urine test for the Histoplasma antigen.The patient later manifested signs and symptoms, including increased ferritin level, fever, splenomegaly, diminished natural killer cell function and heightened interleukin-2 receptor levels, confirming haemophagocytic lymphohistiocytosis. Given the patient's gravely decompensated state, the treatment incorporated dexamethasone, and the patient's vasopressor-resistant septic shock was addressed with methylene blue., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Cryptococcal meningitis (CM) causes substantial mortality in African countries with a high prevalence of human immunodeficiency virus (HIV), despite advances in disease management and increasing antiretroviral therapy (ART) coverage. Reliable diagnosis of CM is cheap and more accessible than other indicators of advanced HIV disease burden such as CD4 testing or investigation for disseminated tuberculosis; therefore, monitoring CM incidence has the potential to serve as a valuable metric of HIV programmatic success., Methods: Botswana national meningitis surveillance data from 2015 to 2022 were obtained from electronic health records. All electronic laboratory records from cerebrospinal fluid samples analyzed within government healthcare facilities in Botswana were extracted from a central online repository. Adjustments for missing data were made through triangulation with prospective cohort study datasets. CM case frequency was enumerated using a case definition and incidence calculated using national census data., Results: A total of 1744 episodes of CM were identified; incidence declined from 15.0 (95% confidence interval [CI], 13.4-16.7) cases/100 000 person-years in 2015 to 7.4 (95% CI, 6.4-8.6) cases/100 000 person-years in 2022. However, the rate of decline slowed following the introduction of universal treatment in 2016. The highest incidence was observed in men and individuals aged 40-44 years. The proportion of cases diagnosed through cryptococcal antigen testing increased from 35.5% to 86.3%., Conclusions: CM incidence has decreased in Botswana following expansion of ART coverage but persists at a stubbornly high incidence. Most cases are now diagnosed through the cheap and easy-to-use cryptococcal antigen test, highlighting the potential of using CM as key metric of program success in the Treat All era., Competing Interests: Potential conflicts of interest. J. M. and J. N. J. have received investigator-initiated funding from bioMérieux. J. N. J. has received grants from the Centers for Disease Control and Prevention (CDC). D. S. L. has received salary support from Janssen, CDC, and NIHR. A. A. has received research support from ViiV Healthcare; research support and support for meetings and/or travel from Viatris Pharmaceuticals; contract from Botswana Harvard Health Partnership; consulting fees from UNAIDS; participation on an advisory board and support for meetings and/or travel from the World Health Organization; and membership on the University of Botswana Institutional Review Board. S. E. reports support for meetings and/or travel from the International AIDS Society. J. O. reports support for meetings and/or travel from the Clinton Health Access Initiative. I. M. reports support for meetings and/or travel from the Jill & Herbert Hunt Scholarship, Oxford University. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Opportunistic infections in the central nervous system (CNS) can be a serious threat to people living with HIV. Early aetiological diagnosis and targeted treatment are crucial but difficult. Metagenomic next-generation sequencing (mNGS) has significant advantages over traditional detection methods. However, differences in the cerebrospinal fluid (CSF) microbiome profiles of patients living with and without HIV with suspected CNS infections using mNGS and conventional testing methods have not yet been adequately evaluated., Methods: We conducted a retrospective cohort study in the first hospital of Changsha between January 2019 and June 2022 to investigate the microbiomes detected using mNGS of the CSF of patients living with and without HIV with suspected CNS infections. The pathogens causing CNS infections were concurrently identified using both mNGS and traditional detection methods. The spectrum of pathogens identified was compared between the two groups., Results: Overall, 173 patients (140 with and 33 without HIV) with suspected CNS infection were enrolled in our study. In total, 106 (75.7%) patients with and 16 (48.5%) patients without HIV tested positive with mNGS (p = 0.002). Among the enrolled patients, 71 (50.7%) with HIV and five (15.2%) without HIV tested positive for two or more pathogens (p < 0.001). Patients with HIV had significantly higher proportions of fungus (20.7% vs. 3.0%, p = 0.016) and DNA virus (59.3% vs. 21.2%, p < 0.001) than those without HIV. Epstein-Barr virus (33.6%) was the most commonly identified potential pathogen in the CSF of patients living with HIV using mNGS, followed by cytomegalovirus (20.7%) and torque teno virus (13.8%). The top three causative pathogens identified in patients without HIV were Streptococcus (18.2%), Epstein-Barr virus (12.1%), and Mycobacterium tuberculosis (9.1%). In total, 113 patients living with HIV were diagnosed as having CNS infections. The rate of pathogen detection in people living with HIV with a CNS infection was significantly higher with mNGS than with conventional methods (93.8% vs. 15.0%, p < 0.001)., Conclusion: CSF microbiome profiles differ between patients living with and without HIV with suspected CNS infection. mNGS is a powerful tool for the diagnosis of CNS infection among people living with HIV, especially in those with mixed infections., (© 2024 British HIV Association.)

Histoplasmosis is a frequent cause of infections in people living with HIV/AIDS (PLWHA). This study introduces the application of a Histoplasma capsulatum urine antigen lateral flow assay (LFA) for diagnosing disseminated histoplasmosis in PLWHA in Suriname. The LFA's diagnostic accuracy was compared with the current diagnostic approach, aiming to assess whether this test resulted in improved early detection and management. Additionally, the prevalence of histoplasmosis among advanced stage HIV patients without clinical suspicion of infection was evaluated using the same LFA. In total, 98 patients were included in the study, of which 58 were classified as "possible disseminated histoplasmosis (DH)" based on clinical criteria and 40 as "controls". Of these possible DH cases, only 19 (32.7%) had a positive LFA. During the study, decisions for treatment were made without the treating physician being aware of the LFA result. Only 55% of the patients who started treatment for histoplasmosis based on clinical criteria had a positive LFA, and 21% of untreated patients had a positive LFA. This study shows that combining clinical signs with LFA results enhances diagnostic accuracy and is cost effective, resulting in better treatment decisions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Woittiez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: In Latin America, tuberculosis (TB) and histoplasmosis are two of the most frequent opportunistic infections affecting people living with human immunodeficiency virus (HIV). However, there are limited data on the clinical characteristics and outcomes of patients with concurrent TB and histoplasmosis infections., Methods: This was a retrospective observational study to describe the clinical, epidemiological and laboratory characteristics and outcomes of 21 patients living with HIV (PLHIV) who were diagnosed with concurrent histoplasmosis and TB between 2017 and 2021 in Guatemala City, Guatemala., Results: Most patients were male and were newly diagnosed with HIV. All patients had advanced HIV disease (AHD). They presented with a median CD4 count of 20 cells/µl. The most common symptoms reported by the patients were fever, weight loss, cough and diarrhoea. Twelve patients died within 6 months of baseline evaluation, for a mortality rate of 57.1%., Conclusions: PLHIV with concurrent TB and histoplasmosis infections are characterised by AHD, predominantly presenting with disseminated forms of these infections and with unspecific symptoms and signs. This evidence calls for early HIV and opportunistic infection screening and insights into the challenges and opportunities for the efficient diagnostic and therapeutic management of patients with AHD with concurrent histoplasmosis and TB infections., (© The Author(s) 2024. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Background: Cryptococcosis is an invasive, opportunistic fungal infection seen especially in human immunodeficiency virus (HIV) infected patients. Cryptococcal meningitis (CM) is the second leading cause of mortality in HIV patients. We report a case of disseminated cryptococcosis presenting with altered mental status in a newly diagnosed HIV infection., Methods and Results: A 50-year-old with a short history of altered mental sensorium and a history of low-grade fever and weight loss for few months presented at a tertiary care hospital in North India. He was detected positive for HIV-1. Cryptococcal antigen (CRAG) was positive in Cerebrospinal fluid (CSF), and negative in serum. The fungal culture in CSF was sterile while the fungal blood culture grew Cryptococcus neoformans. The patient was treated with single high-dose Liposomal Amphotericin B (LAmB) therapy followed by Fluconazole and Flucytosine for the next two weeks followed by fluconazole daily for consolidation and maintenance therapy. Antiretroviral therapy (ART) was started 4 weeks after induction therapy. After 6 months, the patient is doing fine., Conclusion: Single dose LAmB along with the backbone of fluconazole and flucytosine appears promising in disseminated cryptococcal infection in HIV-infected individuals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: In countries with access to early antiretroviral treatment (ART), opportunistic infections caused by cytomegalovirus (CMV) in people living with HIV (PLWH) are becoming increasingly rare. As potential complications are severe, it is critical to remain aware of this important diagnosis. However, clinical characteristics and prognosis of CMV infection in PLWH in the era of modern ART have not been well described., Methods: Here, we compiled the clinical presentation, management and outcome of CMV infection in PLWH treated at the infectious diseases clinic of Karolinska University Hospital during 2010-2020., Results: We identified 51 cases of active CMV infection, based on detection of CMV-DNA, mainly diagnosed in patients with CD4 T-cell count <200 cells/μL (86%). Median time from HIV diagnosis to detection of CMV infection was 16 days. In 20 cases (39%), CMV infection was symptomatic with retinitis identified as a manifestation in 70% of cases. Symptomatic CMV infection was treated for 73 (20-313) days upon diagnosis, mostly using valganciclovir. One-year mortality was 22% and was associated with longer time to ART initiation from HIV diagnosis and with comorbidities, but not with CMV-DNA levels or CD4 count. Immune reconstitution was not significantly compromised in patients with symptomatic CMV, although CD4/8 ratio tended to be lower in patients with systemic CMV infection., Conclusions: Retinitis remains the most common manifestation of symptomatic CMV infection in PLWH. Recognizing CMV infection is important, especially in the management of 'late presenters'. Adequate duration of antiviral therapy and appropriate follow-up must be ensured to avoid complications., (© 2024 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Background: HIV-associated tuberculosis (TB) contributes disproportionately to global tuberculosis mortality. Patients hospitalised at the time of the diagnosis of HIV-associated disseminated TB are typically severely ill and have a high mortality risk despite initiation of tuberculosis treatment. The objective of the study is to assess the safety and efficacy of both intensified TB treatment (high dose rifampicin plus levofloxacin) and immunomodulation with corticosteroids as interventions to reduce early mortality in hospitalised patients with HIV-associated disseminated TB., Methods: This is a phase III randomised controlled superiority trial, evaluating two interventions in a 2 × 2 factorial design: (1) high dose rifampicin (35 mg/kg/day) plus levofloxacin added to standard TB treatment for the first 14 days versus standard tuberculosis treatment and (2) adjunctive corticosteroids (prednisone 1.5 mg/kg/day) versus identical placebo for the first 14 days of TB treatment. The study population is HIV-positive patients diagnosed with disseminated TB (defined as being positive by at least one of the following assays: urine Alere LAM, urine Xpert MTB/RIF Ultra or blood Xpert MTB/RIF Ultra) during a hospital admission. The primary endpoint is all-cause mortality at 12 weeks comparing, first, patients receiving intensified TB treatment to standard of care and, second, patients receiving corticosteroids to those receiving placebo. Analysis of the primary endpoint will be by intention to treat. Secondary endpoints include all-cause mortality at 2 and 24 weeks. Safety and tolerability endpoints include hepatoxicity evaluations and corticosteroid-related adverse events., Discussion: Disseminated TB is characterised by a high mycobacterial load and patients are often critically ill at presentation, with features of sepsis, which carries a high mortality risk. Interventions that reduce this high mycobacterial load or modulate associated immune activation could potentially reduce mortality. If found to be safe and effective, the interventions being evaluated in this trial could be easily implemented in clinical practice., Trial Registration: ClinicalTrials.gov NCT04951986. Registered on 7 July 2021 https://clinicaltrials.gov/study/NCT04951986., (© 2024. The Author(s).)

Background: Immunodeficient patients, particularly HIV patients, are at risk of opportunistic infections. Nontuberculous mycobacteria can cause severe complications in immunodeficient patients., Case Presentation: We describe a 57-year-old HIV patient, primarily presented with coughs and constitutional symptoms, with a unique Mycobacterium genavense abdominal, pulmonary, and central nervous system infection, accompanied by intracranial masses., Conclusion: The diagnosis of NTM, including M. genavense, must always be considered by clinicians in immunodeficient patients, especially those with HIV, who have a compromised immune system., (© 2024. The Author(s).)

Introduction: Management of patients living with Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (AIDS) (PLWHA) still represents a challenge for doctors in various medical fields. The presence of co-infections, with different degrees of immune system impairment, raises the need for a multi-disciplinary approach to the PLWHA. Methods: In this paper, we present three cases of PLWHA with various ophthalmological conditions, who were admitted to "Prof. Dr. Matei Balș" National Institute for Infectious Diseases (INBIMB). Three of them were late presenters, recently diagnosed with AIDS. All three were in immuno-virological failure. The ophthalmic conditions were either related to the HIV infection, or the result of other complications. Discussion: The diversity and complexity of ocular involvement in PLWHA were deeply linked to the patient's immunological status at the ophthalmological evaluation moment. Thus, antiretroviral therapy (ART) played an important immune status recovery role. Encountered ocular conditions vary, some being directly caused by the presence of the virus, and the others were the result of opportunistic infections (cytomegalovirus, Varicella virus) or other co-infections (Treponema pallidum). Neurological conditions disturbing the natural defense mechanism, prolonged hospital stay, and exposure to multiple antibiotic regimens are risk factors for difficult-to-treat eye infections with multidrug-resistant bacteria. Some ocular conditions can be the reason that leads to HIV infection diagnosis, while others can appear during the time, especially in patients with low ART adherence. The prognostic is conditioned by the early recognition and correct management of the disease and the immunological status recovery under ART. Conclusions: Correct and early diagnosis of HIV-related eye conditions is mandatory to establish the most appropriate medical management to obtain an increase in the quality of life of the patient. Abbreviations: HIV = Human Immunodeficiency Virus, AIDS = Acquired Immunodeficiency Syndrome, ART = Antiretroviral Therapy., (#x00A9; The Authors.Romanian Society of Ophthalmology.)

Introduction: Ocular involvement in human immunodeficiency virus (HIV) infected and treatment-experienced patients is a significant concern, despite the advancements in antiretroviral therapy (ART) medication. The extended life expectancy of HIV patients has altered the spectrum of HIV-associated ocular diseases, ranging from minor issues to severe vision impairment or blindness. Therefore, understanding these complications becomes crucial in providing comprehensive medical care and quality of life improvement. HIV patients on multiple ARTs can experience various ocular disorders due to the complexity of their treatment regimens, drug toxicities, immune reconstitution, and opportunistic infections. Most worthy to consider are: cytomegalovirus (CMV) retinitis, immune recovery uveitis (IRU), keratoconjunctivitis sicca (dry eye syndrome), and HIV-associated neuroretinal disorders. Materials and methods: A retrospective clinical investigation was conducted on HIV/AIDS-infected patients from January 1, 2013, to December 31, 2023. The study included 62 patients over 18 years, who tested HIV-positive via enzyme-linked immunosorbent assay (ELISA) and confirmed by Western blot (WB), with assessments of HIV plasma viral load (VL) and CD4+ T cell counts (CD4). Data collected included demographics, pathological histories, clinical characteristics, blood tests, assessments for opportunistic infections, patient staging, antiretroviral therapy initiation, and disease prognosis. Results: The study found that of most patients, 37 were aged 30-39 (59.7%), with 59.7% males and 40.3% females. Most had been living with HIV for 10-19 years (35.5%). Initial CD4 counts were < 200 cells/mm3 in 46.8% of patients, which improved to 19.3% when the study was done. CMV retinitis prevalence decreased from 46.8% initially to 35.5% despite ART. Other conditions included ocular toxoplasmosis (3.22%), tuberculosis-related uveitis (1,6%), keratoconjunctivitis sicca (19.3%), and HIV retinopathy (29%). Notably, 62.1% of CMV retinitis patients experienced significant visual acuity reduction. Oral valganciclovir was beneficial for patients with CMV disease affecting multiple sites and effective for both induction and maintenance therapy of CMV retinitis. Conclusions: Managing ocular complications in HIV-experienced patients requires a multidisciplinary approach with regular ophthalmologic evaluations, prompt treatment of infections, and continuous monitoring of ART effectiveness. Early detection and intervention are crucial for preserving vision and improving outcomes. The study highlighted the importance of constant monitoring even after viral suppression. Abbreviations: HIV = Human immunodeficiency virus, ART = antiretroviral therapy, CMV = cytomegalovirus, IRU = immune recovery uveitis, ELISA = enzyme-linked immunosorbent assay, WB = Western Blot, VL = viral load, CD4 = CD4+ T cells., (#x00A9; The Authors.Romanian Society of Ophthalmology.)

Background: Cryptococcal meningitis (CM), an opportunistic fungal infection affecting immunocompromised hosts, leads to high mortality. The role of previous exposure to glucocorticoids as a risk factor and as an outcome modulator has been observed, but systematic studies are lacking., Objective: The primary aim of this study is to evaluate the impact of glucocorticoid use on the clinical outcomes, specifically mortality, of non-HIV and non-transplant (NHNT) patients diagnosed with CM., Methods: We queried a global research network to identify adult NHNT patients with CM based on ICD codes or recorded specific Cryptococcus CSF lab results with or without glucocorticoid exposure the year before diagnosis. We performed a propensity score-matched analysis to reduce the risk of confounding and analysed outcomes by glucocorticoid exposure. We used a Cox proportional hazards model for survival analysis., Results: We identified 764 patients with a history of glucocorticoid exposure and 1267 patients without who developed CM within 1 year. After propensity score matching of covariates, we obtained 627 patients in each cohort. The mortality risk in 1 year was greater in patients exposed to prior glucocorticoids (OR: 1.3, CI: 1.2-2.0, p = 0.002). We found an excess of 45 deaths among CM patients with previous glucocorticoid use (7.4% increased absolute risk of dying within 1 year of diagnosis) compared to CM controls without glucocorticoid exposure. Hospitalisation, intensive care unit admission, emergency department visits, stroke and cognitive dysfunction also showed significant, unfavourable outcomes in patients with glucocorticoid-exposed CM compared to glucocorticoid-unexposed CM patients., Conclusions: Previous glucocorticoid administration in NHNT patients seems to associate with 1-year mortality after CM adjusted for possible confounders related to demographics, comorbidities and additional immunosuppressive medications. Serial CrAg screening might be appropriate for higher-risk patients on glucocorticoids after further cost-benefit analyses., (© 2024 Wiley-VCH GmbH. Published by John Wiley & Sons Ltd.)

HIV infection alters the skin microbiome and predisposes to a wide range of cutaneous infections, from atypical presentations of common skin infections to severe disseminated infections involving the skin that are AIDS-defining illnesses. Bacterial infection of the skin, most commonly caused by Staphylococcus aureus, occurs frequently and can result in bacteremia. Nontuberculous mycobacterial infections that are usually localized to the skin may disseminate, and guidance on the treatment of these infections is limited. Herpes simplex can be severe, and less common presentations such as herpetic sycosis and herpes vegetans have been reported. Severe herpes zoster, including disseminated infection, requires intravenous antiviral treatment. Viral warts can be particularly difficult to treat, and in atypical or treatment-resistant cases a biopsy should be considered. Superficial candidosis occurs very commonly in people living with HIV, and antifungal resistance is an increasing problem in non-albicans Candida species. Systemic infections carry a poor prognosis. In tropical settings the endemic mycoses including histoplasmosis are a problem for people living with HIV, and opportunistic infections can affect those with advanced HIV in all parts of the world. Most cutaneous infections can develop or worsen as a result of immune reconstitution in the weeks to months after starting antiretroviral therapy. Direct microscopic examination of clinical material can facilitate rapid diagnosis and treatment initiation, although culture is important to provide microbiological confirmation and guide treatment., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Opportunistic infections (OIs) among newly diagnosed HIV patients are a marker for inadequateness of HIV awareness and testing. Despite global efforts at creating awareness for early detection, late HIV diagnosis and its associated OIs still exist. This study sought to determine the prevalence and patterns of OIs and associated factors among newly diagnosed HIV patients in Ghana., Methods: A retrospective study using data extraction was conducted among 423 newly diagnosed HIV patients aged ≥18 years at the Korle-Bu Teaching Hospital from July 1 st 2018 to December 2019. Multivariate logistic regression was adopted to assess factors associated to OIs. Analysis was performed using SPSS version 16, and p-value < 0.05 was deemed significant., Results: The mean age of patients with a new HIV diagnosis was 40.15 ± 11.47 years. Male versus female sex differential was 30.3% and 69.7%, respectively. The prevalence of OIs among newly diagnosed HIV patients was 33.1% (95% CI = 34.6-44.1). About 70% (120/166) of patients with OIs were classified into WHO clinical stage III and IV. The most common OIs were candidiasis (oro-pharyhngeal-esophageal) (36.9%), and cerebral toxoplasmosis (19.9%). The odds of an OI at the time of HIV diagnosis among females was 51% lower than in males (aOR = 0.49, 95% CI = 0.28-0.86). Being employed increased the odds of OIs by 2.5 compared to the unemployed (aOR = 2.5; 95% CI = 1.11-5.61). Participants classified as World Health Organization (WHO) HIV clinical stage III and IV were 15.88 (95% CI = 9.41-26.79) times more likely to experience OIs., Conclusion: One in three patients newly diagnosed with HIV presented with an opportunistic infection, with men more likely to experience such infections. Significant attention should be given to improving case-finding strategies, especially among men., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2024 The Author(s).)

BACKGROUND The highly active antiretroviral treatment (HAART) and the primary prophylaxis in newly diagnosed people living with HIV (PLHIV) have reduced the incidence of opportunistic infections such as cryptococcal meningitis (CM). Relapse of CM is associated with increased morbidity and mortality. The aim of the present case presentation is to report the clinical progress relapse of CM in a man who was a late presenter PLHIV, 1 year after ART initiation with increased CD4 cell count, undetectable viral load, and excellent compliance after disruption of secondary antifungal prophylaxis. CASE REPORT One year after initial diagnosis of HIV and CM, the patient had no neurological or other symptoms, and viral suppression and increased CD4 cell count were achieved. After the completion of 12 months of secondary prophylaxis with fluconazole, an episode of partial seizure with secondary generalization occurred, followed by a short-term memory loss. Magnetic resonance imaging (MRI) indicated a focal lesion in right frontal-parietal brain region. Lumbar puncture was conducted and Cryptococcus neoformans non-resistant to fluconazole was isolated. He received antiepileptic treatment, induction antifungal treatment with liposomal amphotericin and fluconazole, consolidation treatment with fluconazole, and secondary prophylaxis with fluconazole, as in the first episode of CM. One year after the relapse, antiepileptic treatment and secondary prophylaxis with fluconazole continues and no new episode has been reported. The diagnosis of immune reconstitution inflammatory syndrome (IRIS)-related relapse of CM cannot be excluded. CONCLUSIONS Further studies are needed for the evaluation of parameters such as duration of secondary prophylaxis and treatment options for induction and consolidation therapy to reduce the relapse rate of CM.

To date, the identification of crypotococcal relapse remains clinically challenging as it often has similar manifestation with paradoxical immune reconstitution inflammatory syndrome. This study reports on the use of metagenomics assisted next generation sequencing to aid in diagnosing recurrent cryptococcal meningitis in an person living with HIV experiencing recurring symptoms, despite negative culture results for Cryptococcus neoformans in the cerebrospinal fluid. Although fungal culture was negative, when reads from metagenomic and metatranscriptomic sequencing performed on the Day 308 cerebrospinal fluid sample were mapped onto the genome from the Day 4 isolate, 589 specific reads were identified. NCBI BLAST search also revealed Cryptococcus -specific 18S/25S/28S ribosomal RNA, indicating a relapse of the disease.

Objectives: We investigated whether patients with cryptococcal meningitis (CM) or fungaemia detected through South Africa's laboratory cryptococcal antigen (CrAg) screening programme had better outcomes than those presenting directly to the hospital., Methods: We compared 14-day in-hospital case-fatality ratios of HIV-seropositive individuals with CD4 counts below 100 cells/μL and laboratory-confirmed CM/fungaemia from 2017-2021, with or without evidence of a positive blood CrAg test within 14 days prior to diagnosis. We evaluated whether the impact of prior CrAg screening on mortality varied according to the study period (pre-COVID-19: before March 2020 vs. COVID-19: after March 2020)., Results: Overall, 24.5% (830/3390) of patients had a prior positive CrAg test within 14 days of diagnosis. CrAg-screened patients were less likely to have an altered mental status at baseline than non-CrAg-screened patients (38.1% [296/776] vs. 42.6% [1010/2372], p = 0.03), and had a lower crude 14-day case-fatality ratio (24.7% [205/830] vs. 28.3% [724/2560]; OR, 0.83 [95% CI, 0.69-0.99]; p = 0.045). Previous CrAg screening was associated with a greater reduction in the crude 14-day mortality during the COVID-19 period (OR, 0.64 [0.47-0.87]; p = 0.005) compared with before (OR, 0.95 [0.76-1.19]; p = 0.68). After adjustment, previous CrAg screening within 14 days was associated with increased survival only during the COVID-19 period (adjusted OR, 0.70 [0.51-0.96]; p = 0.03)., Discussion: Previous CrAg screening was associated with a survival benefit in patients hospitalized with CM/fungaemia during the COVID-19 period, with fewer patients having an altered mental status at baseline, suggesting that these patients may have been diagnosed with cryptococcosis earlier., (Copyright © 2023 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Despite advances in diagnostic, therapeutic and preventive strategies for HIV, pulmonary diseases continue to be the major cause of morbidity and mortality in infants and children infected with HIV. With effective programs to prevent perinatal HIV-1 transmission to early diagnosis in infants, we have seen a substantial decline in paediatric HIV incidence. Early initiation of Highly Active Anti-Retroviral Therapy (HAART) in all HIV infected children coupled with consistent use of Pneumocystis prophylaxis in all HIV exposed/infected children under 5 years of age has considerably reduced associated infections overall and respiratory infections in particular. In developing countries already burdened with poverty, malnutrition, suboptimal immunization coverage and limited access to health care and treatment, acute and chronic HIV-associated respiratory disease remain a major cause for concern. Prevention of severe respiratory infections in advanced HIV disease among children consists mostly of rapid and optimal HAART initiation & continuation, preventing severe TB disease with BCG and TB preventive treatment, preventing Pneumocystis jirovecii pneumonia with cotrimoxazole prophylaxis and administering age-appropriate vaccinations and catch-up vaccines as per National Immunization schedule., Competing Interests: Conflicts of interest The author has none to declare., (Copyright © 2023 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.)

Objective: Aim: To the aim of our study is to draw attention to the need to take into account HIV infection and its complications, such as CNS toxoplasmosis, in the differential diagnosis of people presenting with impaired consciousness. We analyzed our patient's medical records and available statistical data on HIV infection, as well as literature on nervous system involvement in the course of AIDS., Patients and Methods: Materials and Methods: In our paper, we present the case of a 43-year-old male who was admitted to a neurological ward due to impaired consciousness. Diagnostic imaging and laboratory tests were conducted, and patient was diagnosed with toxoplasmosis in the course of AIDS., Conclusion: Conclusions: HIV infection is a global public health problem. In the absence or ineffectiveness of treatment, it leads to profound immunodeficiency and, consequently, opportunistic infections. One of them is the reactivation of the latent Toxoplasma gondii infection. It is the most common cause of extensive cerebral lesions in patients infected with the HIV virus. In these cases, MRI reveals numerous scattered ring-enhancing lesions. The symptoms are non-specific: headaches, impaired consciousness, convulsions, behavioral changes, and focal neurological deficits. The onset of neurological symptoms may be the first clinically relevant manifestation of AIDS. It is key to diagnose such patients as soon as possible and treat them accordingly.

Background: There is scarce information on AIDS-related cytomegalovirus (CMV) retinitis in middle-income countries. The objectives of this study were to identify the prevalence of active CMV retinitis in severely immunosuppressed people living with HIV (PLWHIV) and to describe its main features., Methods: This retrospective cohort study was carried out at a tertiary center in São Paulo, Brazil. We included hospitalized adults PLWHIV with CD4 count ≤100 cells/μL, ≥ one quantitation of CMV DNA in plasma, and indirect ophthalmoscopy evaluation., Results: Thirty-eight (21.6%) of 176 participants had at least an ophthalmoscopy diagnosis and only 3 (1.7%) individuals presented active CMV retinitis. All these participants were male, and retinitis was asymptomatic in 2 cases. Two participants had extraocular end-organ CMV disease and detectable CMV DNA in plasma., Conclusions: These results show a low prevalence of active CMV retinitis in the evaluated population. However, 2 of 3 participants had asymptomatic active CMV retinitis and a fifth of participants had at least one ophthalmoscopy diagnosis, suggesting the need for routine ophthalmologic evaluation in hospitalized severely immunosuppressed PLWHIV. The profile of participants with active CMV retinitis was similar to that described in the pre-ART era and quantitation of CMV DNA in plasma was variable.

We describe the opportunistic infections (OIs) of HIV/AIDS to understand the spectrum, mortality, and frequency of multiple coinfected OIs among HIV/AIDS patients in southern China, where OIs are severe. We carried out a retrospective cohort study of hospitalized HIV-infected individuals at the Fourth People's Hospital of Nanning, Guangxi, China, from Jan. 2011 to May. 2019. The chi-square test was used to analyze cross-infection; the Kaplan‒Meier analysis was used to compare mortality. A total of 12,612 HIV-infected patients were admitted to this cohort study. Among them, 8982 (71.2%) developed one or more OIs. The overall in-hospital mortality rate was 9.0%. Among the patients, 35.6% coinfected one OI, and 64.4% coinfected more than two OIs simultaneously. Almost half of the patients (60.6%) had CD4 + T-cell counts < 200 cells/μL. Pneumonia (39.8%), tuberculosis (35.3%), and candidiasis (28.8%) were the most common OIs. Coinfected cryptococcal meningitis and dermatitis are the most common combined OIs. The rate of anaemia (17.0%) was highest among those common HIV-associated complications. Multiple OIs are commonly found in hospitalized HIV/AIDS patients in southwestern China, which highlights the need for improved diagnosis and treatment., (© 2022. The Author(s).)

Background: Cryptococcal meningitis is the most common cause of meningitis in adults living with HIV in sub-Saharan Africa. The estimates of national, regional, and global burden of cryptococcal meningitis are essential to guide prevention strategies and determine needs for diagnostic tests and treatments. We present a 2020 estimate of the global burden of HIV-associated cryptococcal infection (antigenaemia), cryptococcal meningitis, and cryptococcal-associated deaths., Methods: We defined advanced HIV disease as adults with a CD4 count of less than 200 cells/μL, as this group is at highest risk for cryptococcosis. We used UNAIDS estimates (2019-20) and population-based HIV impact assessment surveys (2016-18) to estimate the number of adults with CD4 counts of less than 200 cells/μL at risk for cryptococcosis, by country and region. Secondly, we summarised cryptococcal antigenaemia prevalence in those with a CD4 count of less than 200 cells/μL by reviewing published literature. Thereafter, we calculated the number of cryptococcal antigen (CrAg)-positive people in each country and region by multiplying the number with advanced HIV disease at risk for cryptococcal infection by the cryptococcal antigenaemia prevalence of the respective country or region. We estimated progression from cryptococcal antigenaemia to meningitis or death based on estimates from the published literature., Findings: We estimated that there were 4·3 million (IQR 3·0-4·8) adults with HIV and CD4 counts of less than 200 cells/μL globally in 2020. We calculated a mean global cryptococcal antigenaemia prevalence of 4·4% (95% CI 1·6-7·4) among HIV-positive people with CD4 counts of less than 200 cells/μL, corresponding to 179 000 cases (IQR 133 000-219 000) of cryptococcal antigenaemia globally in 2020. Annually, we estimated that there are 152 000 cases (111 000-185 000) of cryptococcal meningitis, resulting in 112 000 cryptococcal-related deaths (79 000-134 000). Globally, cryptococcal disease accounts for 19% (13-24) of AIDS-related mortality., Interpretation: Despite a reduction in the estimated absolute global burden of HIV-associated cryptococcal meningitis compared with 2014, likely to be due to antiretroviral therapy expansion, cryptococcal disease still accounts for 19% of AIDS-related deaths, similar to 2014 estimates. To end cryptococcal meningitis deaths by 2030, cryptococcal diagnostics, meningitis treatments, and implementation of preventive screening are urgently needed., Funding: None., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Talaromycosis is among common opportunistic infections in patients with AIDS living in the endemic area, although the incidence is declining in the era of antiretroviral therapy. Here, we present a case of disseminated infection in a patient who was unaware of HIV-serostatus and did not receive antiretroviral therapy., Competing Interests: Conflict of interest The authors have no competing interests to declare., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Opportunistic infections (OI) are common in patients with acquired immunodeficiency syndrome (AIDS). Cryptococcus neoformans and Mycobacterium avium complex (MAC) are frequently responsible of such infections. However, concurrent infection with these two pathogens is uncommon and underreported in the literature., Case Description: We describe the case of a 28-year-old Caucasian Belgian patient with no travel history, who presented with low-grade fever, headache and wasting syndrome. He was diagnosed with human immunodeficiency virus (HIV) infection at AIDS stage, with a HIV viral load of 506,000 viral copies/mL and a CD4 + T-cells count of 10 cells/µL. Diagnosis of disseminated Cryptococcus neoformans infection was made by positive serum cryptococcal antigen and positive culture for Cryptococcus neoformans in blood and in cerebrospinal fluid. Diagnosis of disseminated Mycobacterium avium complex infection was made by positive culture on a biopsy of a mediastinal lymph node. With adequate anti-retroviral therapy (ART) and treatment of these OIs, the patient recovered well and had a good clinical evolution., Discussion and Conclusion: To our knowledge, this is the second case of coexistence of these two dangerous OIs reported in the post ART era. Clinicians should be aware that such co-infections still happen in high-income countries, in patients with severe immunodeficiency. Early detection and treatment of HIV is of paramount importance to prevent AIDS and its complications. We highlight the importance of thoroughly excluding all opportunistic infections in patients with newly diagnosed AIDS. Abbreviations: ABC: abacavir; AIDS: acquired immunodeficiency syndrome; AFB: acid-fast bacilli; ART: antiretroviral therapy; CM: cryptococcal meningitis; CrAg: cryptococcal antigen; CSF: cerebrospinal fluid; CT: computed tomography; EACS: European AIDS Clinical Society; FTC: emtricitabine; HIC: high-income countries; HIV: human immunodeficiency virus; HIV-VL: HIV-viral load; ICP: intracranial pressure; IRIS: immune reconstitution inflammatory syndrome; MAC: Mycobacterium avium complex; MRI: magnetic resonance imaging; MSM: man who has sex with men; NR: normal range; OD: omne in die = once daily; OI: opportunistic infection; RAL: raltegravir; TAF: tenofovir alafenamide fumarate.

BACKGROUND The iceberg phenomenon (in which the most of a problem is invisible) of people living with HIV/AIDS, particularly those with unknown HIV status, has been epidemiologically challenging. Central nervous system (CNS) opportunistic infections in patients with HIV/AIDS are one of the leading causes of morbidity and mortality in people living with HIV/AIDS. There are currently limited data on the immunogenicity, safety, and efficacy of COVID-19 vaccines in people living with HIV/AIDS with its associated opportunistic CNS infections as well as those without antiretroviral treatment. CASE REPORT Two young men with previously unknown HIV status and its related opportunistic infections received their first doses of COVID-19 vaccine (Vero Cell), inactivated. Both patients had the risk factor of having sex with men (men who have sex with men). Fever and first neurological symptoms occurred within the first few days after vaccination. Both patients were hospitalized and were tested positive for HIV for the first time. Both were further diagnosed from brain imaging as having CNS opportunistic infections. A presumptive diagnosis of cerebral toxoplasmosis was established as the working diagnosis according to the laboratory and epidemiological factors. Despite the treatment, neurological and clinical deficits worsened and eventually led to death in both patients. CONCLUSIONS The causality analyses showed that both adverse events had a possible inconsistent causal relationship to COVID-19 vaccination. Our cases may reflect the need for further studies on the safety of COVID-19 vaccines in people with HIV/AIDS-associated CNS opportunistic infection as well as people with HIV/AIDS who never receive antiretroviral treatment (ART).

Background: Histoplasmosis is the most common endemic mycosis among people living with advanced HIV infection., Purpose: Describe general aspects and challenges of this disease and its association with HIV., Research Design: Review of literature., Study Sample: Articles found using different combinations of terms including "disseminated histoplasmosis" and AIDS/HIV or immunosuppression in PubMed, Scopus, WHO Global health library, and Scielo database., Analysis: We look for information on epidemiology, pathogenesis, diagnosis, and treatment of histoplasmosis in AIDS patients., Results: Histoplasmosis is caused by Histoplasma capsulatum , a dimorphic fungus encountered throughout the world, mainly in soil enriched with bat and bird excreta. Progressive disseminated histoplasmosis is the main presentation of this mycosis in people living with advanced HIV and is fatal if left untreated. Symptoms include a systemic disease characterized by fever, weight loss, night sweats, skin manifestations, hepatomegaly, splenomegaly, and septic shock. Diagnostic tests include culture, visualization of H. capsulatum by direct and histopathological examination, serology, antigen, molecular, and skin testing. Patients with disseminated disease require aggressive and prolonged treatment to eradicate the pathogen and include amphotericin B and itraconazole. In many low income countries of endemic regions, histoplasmosis in HIV-positive patients is often undiagnosed or misdiagnosed as another opportunistic infection, due to the similarity in clinical manifestations and to the paucity of better diagnostic tests., Conclusion: Histoplasmosis remains a neglected disease. Few studies about the disease and expensive treatments make it difficult to reduce the morbidity and mortality of this condition. Public health services and physicians must be aware of histoplasmosis' burden among the HIV-positive population.

Objectives: Cryptococcal meningitis constitutes a significant source of mortality in the developing world. Annually, approximately 625 000 deaths occur worldwide among patients with human immunodeficiency virus (HIV) infection. This study aims to assess the cost-effectiveness of implementing cryptococcal antigen lateral flow assay (CRAG-LFA) screening in Brazil compared with the current practice., Methods: An economic evaluation using a Monte Carlo microsimulation was conducted, considering the perspective of the Brazilian Public Health System, to calculate the cost-effectiveness of 4 diagnosis tests: (1) CRAG-LFA, (2) the cryptococcal antigen latex agglutination (CRAG-LA) test, (3) India ink, and (4) nontracking as a baseline. The time horizon comprised 1 year for the intervention and 5 years for the budgetary impact analysis. Two primary effectiveness outcomes were considered: years of life and quality-adjusted life-years., Results: CRAG-LFA has extended dominance vis à vis CRAG-LA and India ink. CRAG-LFA would cost $418.46 more than CRAG-LA for the treatment of each symptomatic patient living with HIV, with an incremental cost effectiveness ratio of $2478.75/quality-adjusted life year. The budgetary impact analysis estimated that the incorporation of CRAG-LFA would have an additional cost of $1 959 236.50 in 5 years., Conclusions: These findings suggest that, for patients living with HIV in the Brazilian Public Health System, the adoption of CRAG-LFA screening is cost-effective compared with the use of CRAG-LA and India ink. It represents an opportunity to prevent cryptococcal meningitis and its mortality in Brazil., (Copyright © 2021 ISPOR--The professional society for health economics and outcomes research. Published by Elsevier Inc. All rights reserved.)

Introduction: Penicillium marneffei is one of the most common opportunistic infectious fungi associated with AIDS (Acquired Immunodeficiency Syndrome). It is prevalent in Southeast Asia and southern China (such as Guangdong), but rare in inland provinces of China. Penicillium marneffei infections are often misdiagnosed., Case Report: Here, we report a patient with Penicillium marneffei infection from Shaanxi Province, China, who was previously repeatedly diagnosed as Kala-azar in two hospitals. The patient received medical treatment due to fever and multiple papules, worked as a tour guide, and had travel history in Southeast Asian countries. We performed nanopore genome sequencing on blood samples of the patient and obtained 84,000 reads in 3.5 hours. The average length of the sequences was 7088.7 bases and the longest sequence was 87471 bases. Through comparison with the pathogenic bacteria database, 13 homologous Penicillium marneffei sequences were identified. Furthermore, by using specific quantitative real time-polymerase chain reaction of Penicillium marneffei, fungal ITS (Internal Transcribed Spacer) sequencing, and fungal biphasic culture, we further confirmed the pathogen as Penicillium marneffei. Meanwhile, the patient was confirmed to be HIV (Human Immunodeficiency Virus) positive. Thus, the patient was diagnosed with AIDS combined with Penicillium marneffei infection, which, to the best of our knowledge, is the first report of Penicillium marneffei infection in Shaanxi Province, China., Conclusions: Metagenomic analysis based on nanopore sequencing provides an important reference for the diagnosis of Penicillium marneffei infection in this case., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2022 Dongli Liu, Lin Ma, Lingfeng Mao, Yiqun Wang, Long Ding, Anli Wang.)

We evaluated disseminated histoplasmosis (DH) in HIV patients over 10 years in southern Brazil. The incidence was 12 cases/1,000 hospitalizations (2010-2019); the mortality rate was 35%. Tuberculosis frequently obscured the diagnosis of DH. We emphasize the need in our region to suspect and investigate DH using more sensitive methods.

Background and Objectives : Patients living with HIV (PLWH), especially those diagnosed too late or not receiving treatment with antiretroviral drugs in the stage of advanced immunodeficiency AIDS for various reasons, develop additional opportunistic infections or AIDS-defining diseases that may contribute directly to the death of these patients. Material and Methods : In this work, we focused on disorders of the central nervous system (CNS) by retrospectively analyzing the symptoms, clinical and autopsy diagnoses of patients diagnosed with HIV infection who died in the provincial specialist hospital in the Lower Silesia region in Poland. Results : The autopsy was performed in 27.4% cases. The cause of death was determined to be HIV-related/AIDS-associated in 78% patients. The most common AIDS-defining CNS diseases in our cohort were toxoplasmosis and cryptococcosis. Conslusions : The presented results of the most common causes of changes in the central nervous system among deceased HIV-infected patients are comparable to the results of studies by other scientists cited in the publication.

Background: Human immunodeficiency virus (HIV) infected individuals are prone to opportunistic infections (OIs) due to HIV mediated immune suppression. When opportunistic infections occur in the form of relapse or reinfection, it is said to be reoccurrence. This study was aimed to assess Incidence and predictors of reoccurrence of opportunistic infections among adult people living with HIV (PLHIV) attending ART clinics in Arba Minch Town, Southern Ethiopia., Methods: This retrospective cohort study was conducted on 450 HIV/AIDS patients attending anti-retro viral therapy (ART) clinics in Arba Minch town, southern Ethiopia. Simple random sampling technique was used. Kaplan-Meier graph and log rank test were used for group wise comparison. Bivariate and multivariable Cox Proportional Hazard Regression model were used to identify independent predictors of reoccurrence of opportunistic infection., Result: One hundred nineteen HIV/AIDS patient had reoccurrence of opportunistic infection. The incidence rate was 11.5 per 1000 person months. The mean time of reoccurrence was 56 months. One of the most reoccurred OIs was pulmonary tuberculosis (PTB). Predictors that were associated significantly were recent cell differentiation 4 (CD4) count, recent body mass index (BMI), recent functional status, and duration on anti-retroviral therapy (ART)., Conclusion: Though the incidence rate of OIs decreased from previous findings, attention should be given to HIV patients with low CD4 count, low BMI and for those bedridden patients., Competing Interests: The authors have declared that no competing interests exist.

Background: People living with advanced HIV disease are at high risk of morbidity and mortality. We assessed the prevalence of cryptococcal antigenemia (CrAg) and clinical outcomes among patients newly presenting with CD4 ≤100 cells/μL in Vietnam., Setting: Twenty-two public HIV clinics in Vietnam., Methods: During August 2015-March 2017, antiretroviral therapy (ART)-naïve adults presenting for care with CD4 ≤100 cells/μL were screened for CrAg. Those who consented to study enrollment were followed up for up to 12 months and assessed for clinical outcomes., Results: Of 3504 patients with CD4 results, 1354 (38.6%) had CD4 ≤100 cells/μL, of whom 1177 (86.9%) enrolled in the study. The median age was 35 years (interquartile range 30-40); 872 (74.1%) of them were men, and 892 (75.8%) had CD4 <50 cells/μL. Thirty-six patients (3.1%) were CrAg-positive. Overall, 1151 (97.8%) including all who were CrAg-positive initiated ART. Of 881 patients (76.5%) followed up for ≥12 months, 623 (70.7%) were still alive and on ART at 12 months, 54 (6.1%) had transferred to nonstudy clinics, 86 (9.8%) were lost to follow-up, and 104 (11.8%) had died. Among all 1177 study participants, 143 (12.1%) died, most of them (123, 86.0%) before or within 6 months of enrollment. Twenty-seven patients (18.9%) died of pulmonary tuberculosis, 23 (16.1%) died of extrapulmonary tuberculosis, 8 (5.6%) died of Talaromyces marneffei infection, and 6 (4.2%) died of opioid overdose. Eight deaths (5.8%) occurred among the 36 CrAg-positive individuals., Conclusions: Late presentation for HIV care was common. The high mortality after entry in care calls for strengthening of the management of advanced HIV disease., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: Histoplasmosis and cryptococcosis are important public health problems in people living with HIV (PLHIV) in Central America. Conventional laboratory tests, such as culture and microscopy, are not optimal; however, antigen (Ag) tests are rapid, highly sensitive, and specific for diagnosis of fungal opportunistic infections (OI). The aim of this study was to describe the results of a laboratory-based surveillance system for histoplasmosis and cryptococcosis., Methods: An observational cross-sectional study based on laboratory surveillance, was carried out in two hospitals in Guatemala and one hospital in El Salvador, between July 2012 and December 2014. Diagnosis of histoplasmosis and cryptococcosis in PLHIV were performed by culture and Ag test., Results: A total of 160 PLHIV were diagnosed with fungal OI, of which, 96 (60%) were diagnosed with histoplasmosis, 62 (39%) were with cryptococcosis, and two patients (1%) were diagnosed with both fungal diseases. Of the 160 patients analysed in this study, 94 (59%) were diagnosed using only an Ag assay. CD4 cell count data were available for 136 (85%) patients; 127 (93%) patients had a CD4 count <200; and 90 (66%) had counts <50 CD4 cells per µl. Antiretroviral therapy utilisation at diagnosis was low (33%). Seventy-one out of 160 (44%) were co-infected with tuberculosis or other OIs., Conclusion: More than half of the patients in this study were diagnosed only by rapid laboratory Ag tests. A high per cent of the patients had advanced HIV disease., (© 2021 The Authors. Mycoses published by Wiley-VCH GmbH.)

Objectives: The World Health Organization recommends routinely screening HIV-infected patients with CD4 + T-cell counts <100/μL for cryptococcal infection to prevent cryptococcal meningitis (CM), based on studies in Sub-Saharan Africa where the prevalence of positive cryptococcal antigen (CrAg+) is ≥ 3% in this subgroup. Data about such prevalence in Spain are unavailable and rare in other European countries. Thus, the Spanish AIDS Study Group guidelines do not recommend routinely screening. We aim to determine the prevalence and outcomes of cryptococcal infection in this subgroup of patients in Spain., Methods: We determined CrAg using a lateral flow assay in banked plasma from participants in the cohort of the Spanish AIDS Research Network. Eligible patients had CD4 + T-cell counts ≤100/μL at the time of plasma collection and a follow-up >4 weeks, unless they died., Results: We included 576 patients from June 2004 to December 2017. Of these, 43 were CrAg+ for an overall prevalence of 7.5%. There were no differences depending on birthplace. The CrAg+ was independently associated with a higher mortality at eight weeks (hazard ratio (HR) 5.36, 95% confidence interval (CI) 1.46-19.56) and 6 months (HR 3.12, 95% CI 1.19-8.21). CM was reported in 10 of the 43 CrAg+ patients. There were no cases among negatives. Five patients had CM when the plasma was collected and five developed it during the follow-up. The number of subjects needed to screen to anticipate the diagnosis of one CM case was 114., Conclusions: The CrAg+ prevalence among HIV-infected patients with CD4 + T-cell counts ≤100/μL diagnosed in Spain, both immigrants and native-born Spanish, is >7%. Consequently, the Spanish AIDS Study Group guidelines have to be updated and recommend routine screening for cryptococcal infection in these patients. Future studies should explore whether this recommendation could be firmly applied to other European populations., (Copyright © 2020 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Cryptococcal infection is a frequent cause of mortality in Brazilian HIV-infected patients. The present study aimed to evaluate the cost-effectiveness and budgetary impact of four cryptococcosis screening strategies in HIV-infected patients with CD4+ ≤ 200 cells/mm3, in Brazil. A Monte Carlo microsimulation was used to compare the following diagnostic tests: a systematic serum cryptococcal antigen (CRAG) screening with latex agglutination (CRAG-LA), a lateral flow immunochromatographic test (CRAG-LFA), India ink staining and no intervention. The rationale was that of the Unified Health System (SUS), and the time horizon was of one year for the intervention and of five years for the budgetary impact analysis (BIA). The effectiveness outcomes were years of life and years of life adjusted for quality (QALY). The cost-effectiveness analysis showed that the two cryptococcal antigen tests were cost-effective, presenting with superior results in comparison with India ink and no screening. CRAG-LFA, compared to CRAG-LA, has an incremental cost of US$0.25 and an incremental cost-effectiveness ratio of US$73.36 (considering the US dollar equal to 5 reais, the Brazilian current money). The probabilistic sensitivity analysis between CRAG-LFA and CRAG-LA, despite showing a high agreement between the two tests, indicated the superiority of CRAG-LFA. The BIA estimated that the incorporation of CRAG-LFA would have an additional cost of approximately U$S 10.4 million dollars in five years. These findings suggest that, for the group of studied patients, the adoption of CRAG-LFA and CRAG-LA are cost-effective, while the India ink test and no intervention are less effective strategies. The BIA showed that using the CRAG-LFA test for people living with HIV (PLHIV) with CD4+ ≤ 200 cells/mm3 could reduce costs for the Brazilian Unified Health System (SUS).

Increasing the CD4-count threshold for cryptococcal antigen (CrAg) screening from ≤100 to ≤200 cells/µL resulted in a 3-fold increase in numbers screened. CrAg-prevalence was 3.5% at CD4 101-200 and 6.2% ≤100 cells/µL. Six-month mortality was 21.4% (9/42) in CrAg-positive CD4 ≤100 cells/µL and 3.2% (1/31) in CrAg-positive CD4 101-200 cells/µL., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Cryptococcal antigen (CrAg) detection could direct the timely initiation of antifungal therapy. We searched MEDLINE and Embase for studies where CrAg detection in serum/cerebrospinal fluid (CSF) and CSF fungal culture were done on adults living with human immunodeficiency virus (HIV) who had suspected cryptococcal meningitis (CM). With Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2), we evaluated the risk of bias in 11 included studies with 3600 participants, and used a random-effects meta-analysis to obtain summary sensitivity and specificity of serum and CSF CrAg, as well as agreement between CSF CrAg and CSF culture. Summary sensitivity and specificity of serum CrAg were 99.7% (97.4-100) and 94.1% (88.3-98.1), respectively, and summary sensitivity and specificity of CSF CrAg were 98.8% (96.2-99.6) and 99.3% (96.7-99.9), respectively. Agreement between CSF CrAg and CSF culture was 98% (97-99). In adults living with HIV who have CM symptoms, serum CrAg negativity may rule out CM, while positivity should prompt induction antifungal therapy if lumbar puncture is not feasible. In a first episode of CM, CSF CrAg positivity is diagnostic., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Cytomegalovirus retinitis (CMVR) is an important opportunistic infection (OI) occurring mainly in patients with acquired immunodeficiency syndrome (AIDS) and has the potential to cause severe visual impairment and blindness among AIDS patients. Subsequent to the adoption and implementation of widespread antiretroviral therapy (ART), the prognosis of AIDS-associated CMVR has been substantially improved. Nevertheless, the equivocal clinical evidence as regards the optimal timing for ART initiation in patients with an established CMVR diagnosis is required. We therefore designed the present study in order to investigate the optimal timing for ART initiation in AIDS/CMVR patients., Methods: This will be a prospective, randomized controlled trial to be performed at 17 hospitals in mainland China. A total of 300 participants with CMVR will be randomly assigned to an early ART initiation group (ART initiation within 2 weeks after anti-CMV therapy), or a deferred ART initiation group (initiation of ART more than 2 weeks after anti-CMV therapy) at a 1:1 ratio. All participants will receive 48 weeks of follow-up after anti-CMV therapy initiation. Our primary outcome will be the incidence of visual loss (to a visual acuity worse than 20/40 or 20/200) in the two groups during the 48-week follow-up period. Secondary outcomes will include changes in HIV virological suppression and serum CD4 + T-cell counts, the incidence of mortality, retinitis progression (movement of the peripheral border of a CMV lesion ≥ ½ disc diameter, or occurrence of a new CMV lesion), retinal detachment, immune recovery uveitis (IRU), and other OIs and adverse events between the two study groups during the 48 weeks of follow-up., Discussion: The study aims to investigate the optimal timing for ART initiation in AIDS/CMVR patients. We hope to be able to extract robust clinical evidence for use in optimal AIDS/CMVR management should our trial be successful., Trial Registration: This research was registered as one of the twelve clinical trials under the name of a general project "A study for precision diagnosing and treatment strategies in difficult-to-treat AIDS cases and HIV-infected patients with highly fatal or highly disabling opportunistic infections", ChiCTR1900021195. Registered on 1 February 2019, http://www.chictr.org.cn/showproj.aspx?proj=35362 .