Common Opportunistic Infection Research Articles

Competing risks multi-state model for time-to-event data analysis of HIV/AIDS: a retrospective cohort national datasets, Ethiopia

IntroductionTuberculosis (TB) remains the most common opportunistic infection and leading cause of death among individuals living with HIV/AIDS in Ethiopia. Its significant impact on morbidity and mortality underscores the crucial link between these two diseases. While the advent of antiretroviral therapy (ART) has led to a dramatic decline in mortality rates among HIV/AIDS patients, TB continues to pose a substantial threat. This study aims to estimate the probability of death due to TB among HIV/AIDS patients on ART, considering the presence of various competing risks, including diarrhea, other infections, and unknown/unspecified causes. Also we have assessed the effects of prognostic factors on HIV/AIDS cause specific deaths, compared with the death from other competing risks, and exploring leading cause of death among HIV/AIDS patients on Antiretroviral Therapy.MethodsData from a retrospective research examining the effectiveness of antiretroviral therapy (ART) in Ethiopia were used in this investigation. The data came from medical records of patients who were part of the national ART program. A total of 39,590 records were gathered between October 2019 and March 2020 from all regions of Ethiopia as well as the administration cities of Addis Ababa and Dire Dawa. The study facilities were grouped using a multi-stage sample technique and simple random selection was used to select health facility and a person record from medical records. In the presence of the competing causes of death, Cause specific hazard, subdistribution hazard model and flexible parametric proportional hazard model have been used to assess the effect of covariates on the risk of death, with the cmprisk package in R4.3.2 software.ResultsOut of the total 1212 deaths, 542(44.7%) died competing with other opportunistic infection (TE-Esophageal Candidiasis, TO-oral, CT-CNS Toxoplasmosis, CM-Crypotococcal Meningitis…), 421 (34.7%) died due to tuberculosis and the remaining death were unknown/Not specified infection 222(18.3%) and diarrhea 27(2.2%). Rates of mortality caused by tuberculosis, competing with other opportunistic infection, diarrhea and unknown/Not specified were 3.5, 4.5, 0.2 and 1.8 per 1000 person-months, respectively. Having a higher CD4 count at diagnosis, responding to combination antiretroviral treatment (cART) six months after start, and having prophylactic treatment for pneumocystis pneumonia (PCP) decreased the risk of tuberculosis, other opportunistic infections, and unidentified and diarrheal causes of death. However, older age, late HIV.AIDS diagnosis, and the last HIV/AIDS WHO clinical stages increased the hazard of tuberculosis and other opportunistic disease mortality. Additionally, male gender, older age and last HIV clinical stages increased the mortality HIV/AIDS patients.ConclusionThe findings of this study demonstrated that TB, an opportunistic infection, was the primary cause of death in HIV/AIDS patients, despite the presence of several competing risks, such as diarrhea, other infections, and an undetermined or unclear cause. It's important to use effective techniques to quickly detect those who have HIV or AIDS and provide them with care and treatment to increase their chances of surviving.

Comparison of the BluePoint MoldID oligonucleotide array and Bruker Biotyper MALDI-TOF MS for the identification of filamentous fungi.

The BluePoint MoldID kit is an oligonucleotide array used for the identification of filamentous fungi, and it has not yet been mentioned in recent studies. We used a BluePoint MoldID kit to identify standard and clinical filamentous fungal isolates and compared its performance with that of Bruker MALDI-TOF MS. The former accurately identified 80.2% of the isolates (142/177), and the latter identified 92.6% of the isolates (164/177). The performance of the BluePoint MoldID kit was slightly inferior to that of Bruker MALDI-TOF MS because of the smaller database. However, the BluePoint MoldID kit can cover most clinically common opportunistic fungal infections; thus, it offers an alternative method for laboratories that lack MALDI-TOF MS equipment, as the device is less expensive.

Chinese guidelines for the diagnosis and treatment of human immunodeficiency virus infection/acquired immunodeficiency syndrome (2024 edition).

The Acquired Immunodeficiency Syndrome Professional Group of the Society of Infectious Diseases of the Chinese Medical Association formulated the first edition of the Chinese Guidelines for the Diagnosis and Treatment of human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) (referred to as the Guidelines) in 2005. The 2024 edition of the Guidelines has been compiled by updating the 2021 fifth edition, incorporating the latest research advancements in antiviral therapy, comprehensive management, opportunistic infections, concurrent tumors, and the prevention and intervention of HIV infection. The new edition also introduces a new section on "Incomplete immune reconstitution", proposes the concept of "HIV vulnerable populations" for the first time with recommendations for their diagnosis and treatment. This edition of the Guidelines covers 14sections: epidemiology, pathogenic characteristics, laboratory tests, pathogenesis, clinical presentation and staging, diagnostic criteria, common opportunistic infections, antiretroviral therapy, immune reconstitution inflammatory syndrome, incomplete immune reconstitution, AIDS-related neoplasms, prevention of mother-to-child transmission and conception in serodiscordant couples, pre- and post-exposure prophylaxis, and whole-course management of HIV infection. This edition of the Guidelines aims to assist clinical physicians in making informed decisions in the diagnosis, treatment, and management of HIV/AIDS and will be periodically revised and updated based on domestic and international research progress.

The cGAS-STING pathway in HIV-1 and Mycobacterium tuberculosis coinfection.

Mycobacterium tuberculosis (M. tuberculosis) infection is the most common opportunistic infection in human immunodeficiency virus-1 (HIV-1)-infected individuals, and the mutual reinforcement of these two pathogens may accelerate disease progression and lead to rapid mortality. Therefore, HIV-1/M. tuberculosis coinfection is one of the major global public health concerns. HIV-1 infection is the greatest risk factor for M. tuberculosis infection and increases the likelihood of endogenous relapse and exogenous reinfection with M. tuberculosis. Moreover, M. tuberculosis further increases HIV-1 replication and the occurrence of chronic immune activation, accelerating the progression of HIV-1 disease. Exploring the pathogenesis of HIV-1/M. tuberculosis coinfections is essential for the development of novel treatments to reduce the global burden of tuberculosis. Innate immunity, which is the first line of host immune defense, plays a critical role in resisting HIV-1 and M. tuberculosis infections. The role of the cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway, which is a major DNA-sensing innate immune signaling pathway, in HIV-1 infection and M. tuberculosis infection has been intensively studied. This paper reviews the role of the cGAS-STING signaling pathway in HIV-1 infection and M. tuberculosis infection and discusses the possible role of this pathway in HIV-1/M. tuberculosis coinfection to provide new insight into the pathogenesis of HIV-1/M. tuberculosis coinfection and the development of novel therapeutic strategies.

Opportunistic Infections among People Living with HIV in the Infectious Disease Department, the University Hospital of Fann in Dakar, Senegal

Aim: The aim of this study was to identify the main infections and opportunistic infections in hospitalized patients living with HIV and to determine the hospital lethality rate. Patients and Methods: This was a retrospective, descriptive study of patients hospitalized in the infectious diseases department of the University Hospital of Fann over a 02-year period from 1 January 2021 to 31 December 2022. Results: We recorded 308 cases, 296 of which were patients living with HIV, out of a total of 1208 patients admitted to the department, a hospital prevalence rate of 24.5%. The average age of the patients was 43.3 ± 13.3 years, with a sex ratio of 0.7. One hundred and thirty-one patients (44.26%) were married. 22.97% had no occupation and 35.5% of patients came from home. The average diagnostic period was 3.9 days ± 4.78 days. Two hundred and five patients (69.26%) were at WHO stage 4. Tuberculosis was the most common bacterial infection, with 114 cases (38.5%), followed by common bacterial pneumonia (7.77%) and septicemia (4.72%). With regard to viral infections, the prevalence of viral hepatitis B was 6.76%, followed by herpes (1.68%). Among parasitic infections, toxoplasmosis was noted in 6.41% and cryptosporidiosis in 2.02%. Candidiasis was the most common fungal opportunistic infection, affecting forty-three patients (14.52%), followed by pneumocystis (7.09%) and cryptococcosis (2.36%). More than a third of our patients (37.84%) had severe anaemia, with haemoglobin levels below 8g/dl. Nearly a quarter of patients (21.28%) had impaired kidney function. Conclusion: HIV infection occurs in young adults at a late stage. Mortality remains high due to opportunistic infection. It is essential to carry out early screening, but above all to make available diagnostic tools and certain molecules for treatment of opportunistic infections.

The prevalence of Tuberculosis in HIV patients and their correlation with CD4+ count in a tertiary care hospital in Rishikesh, gateway to the Himalayas

IntroductionTuberculosis is the most common serious opportunistic infection in HIV-positive patients. TB can occur at any time during the course of HIV infection. The estimated number of people living with HIV in India in 2019 was 23.48 lakh. With an estimated 2.5 million cases, or 195 cases per 1 lakh people, India has the highest incidence of tuberculosis cases worldwide, accounting for about 23% of all cases, according to MOHFW India. Information about HIV/TB co-infection is still scarce in India, especially in the hilly areas of Uttarakhand. Material and methodsIn this retrospective study, subjects are the patients who are diagnosed with MTB in HIV-positive patients of all age groups and sex and were followed up from January 2021 till August 2022 in a tertiary referral hospital AIIMS Rishikesh.Diagnosis of MTB was based on clinical, laboratory, and neuroimaging signs, and HIV was based on dot blot, immunochromatographic, and chemiluminescence assay. ResultA total of 520 patients screened for HIV were positive. Out of which 145 were MTB in which 133 had pulmonary tuberculosis and 12 had extra-pulmonary tuberculosis. The patients' average age was 35.5 years. Among males, females and transgender, 97 (66.89%), 46 (31.72%) and 2 (1.38%) have both TB and HIV co-infections respectively.Mean CD4 count prior to ATT was 350.21, After completion was 486.48. The prevalence of Tuberculosis among HIV positive cases was 23.8%.Baseline and latest CD4 count was conducted before and after ART and ATT treatment. It was observed that there was significant increase in the CD4 count after treatment. ConclusionHIV co-infection with TB is higher in this region. There is a role of CD4+ count in the prognosis and progression of the disease. More strategic measures are required for early diagnosis and treatment of HIV to combat MTB.

Incidence and predictors of common opportunistic infections among children living with HIV at Bahir Dar City, Ethiopia

Despite the dramatic decline in the incidence of common opportunistic infections (OIs) after antiretroviral therapy initiation, they remain a significant cause of morbidity and mortality among children with HIV. For better interventions, information regarding the incidence and predictors of common OIs is essential for Children living with HIV. Still, there is a lack of studies in low and middle-income countries, including Ethiopia. Therefore, this study aims to assess the incidence and predictors of common OIs among Children living with HIV on anti-retroviral therapy (ART) at public health institutions in Bahir Dar City, Northwest Ethiopia. The reasons for excluding children not on ART is we want to study the effectiveness of chronic HIV care service, ART drugs and OIs prophylaxis drugs for the prevention of common OIs because it is obvious that the occurrence of OIs in children not on ART and OIs prophylaxis drugs is high. A health institution-based retrospective cohort study was done among 403 Human Immunodeficiency Virus-infected children at public health institutions in Bahir Dar City from 2010 to 2020. Data was entered using Epi-data version 4.6 and analyzed using STATA 14.0. A bivariable Cox-proportional hazards regression model was employed to appreciate the relationship between each explanatory variable with the outcome variable. In the bivariable analysis, variables with a p-value of less than 0.25 were candidates for the multivariable proportional hazard model. The Cox proportional hazards model was used to determine predictors of common opportunistic infections at a 5% significance level. The overall incidence rate of common opportunistic infections was 7.06 with a 95% confidence interval ((CI) 5.78, 9.75) per 100 person-years of observation. Statically significant predictors were World Health Organization (WHO) clinical stage III and IV (adjusted hazard ratio (AHR) = 1.90; (95% CI 1.34, 2.75), having fair/poor adherence to anti-retroviral therapy (ART) (AHR) = 1.80; (95% CI 1.25, 2.94) and hemoglobin level < 10 g/dl (AHR) = 2.00; (95% CI 1.36, 2.89). The overall incidence rate of common OIs among children living with HIV on ART was high. Independent predictors of common OIs among children on ART were advanced-stage of HIV disease, poor ART adherence, and lower hemoglobin level. Therefore, we recommend strongly working on the prevention of advanced stages of HIV disease and improving poor ART adherence to prevent the incidence of OIs among children living with HIV on ART.

Evaluation of Newly Modified Potassium Nitrate Containing Media in Detection and Antibiogram of Mycobacterium tuberculosis

Background: Mycobacterium is a genus of Actinobacteria, given its own family, the Mycobacteriaceae. The genus includes pathogens known to cause serious diseases in mammals, including tuberculosis (Mycobacterium tuberculosis) and the classic Hansen's strain of leprosy (Mycobacterium leprae) [1]. Tuberculosis is the most common life-threatening opportunistic infection (OI) and AIDS defining illness in developing countries [2]. The routine identification methods of tuberculosis includes, Tuberculin skin test, Chest X-ray, Growth and physical characteristics of the bacteria, automated based system such as BACTEC 460 TB method, Mycobacterium growth indicator tube (MGIT) method, MB/BacT system, as well as molecular based techniques as in Amplification of nucleic acid for detection of Mycobacterium tuberculosis [3-6]. Objectives: To evaluate the validity of newly modified potassium nitrate containing medium (NMK) for rapid detection and antibiogram of M tuberculosis. Material and method: This was a health facility based observational diagnostics retrospective study. 125 sputum specimens were investigated to evaluate the validity of newly modified potassium nitrate containing medium for rapid detection and antibiogram of M tuberculosis. Results: 83/125 (66.4%) showed growth after 5-9 days with a mean of 6.58± 0.977 days NMK - containing medium. Conclusions: The NMK - containing medium showed promising results, it showed a positive growth sings and susceptibility results within 5-9 days of inoculation showing much superior than the golden standard LJ medium.

Lung adenocarcinoma concurrent with pulmonary cryptococcosis: a case report and literature review

Pulmonary cryptococcosis (PC) is a common opportunistic fungal infection caused by Cryptococcus neoformans or Cryptococcus gattii. PC primarily invades the respiratory system, followed by the central nervous system. Few clinical reports have examined the coexistence of PC and lung cancer. This study reports the case of a 54-year-old immunocompetent PC patient with lung adenocarcinoma. Chest CT revealed multiple nodules in the right lung, with the largest nodule located in the dorsal segment of the right lower lobe. 18 F‑FDG positron emission tomography-computed tomography (PET-CT) revealed elevated glucose metabolism in the dorsal segment of the right lower lobe, which suggested lung cancer. The metabolism level of the nodule in the basal segment of the right lower lobe and the anterior segment of the right upper lobe was not abnormally increased, but the possibility of a malignant tumour could not be excluded. The pulmonary nodules in the dorsal segment and the basal segment of the right lower lobe were simultaneously resected via video-assisted thoracic surgery (VATS), and the final histopathology revealed primary lung adenocarcinoma and pulmonary cryptococcal infection, respectively. After surgery, antifungal treatment was administered for 3 months. Over the 3-year follow-up, contrast-enhanced computed tomography (CT) revealed no recurrence of either disease. This case study highlights the possibility of dualism in the diagnosis of multiple pulmonary nodules on chest CT, such as the coexistence of lung cancer and PC. Surgical resection is recommended for micronodules that are not easy to diagnose via needle biopsy; in addition, early diagnosis and treatment are helpful for ensuring a good prognosis. This paper reports the clinical diagnosis and treatment of one patient with pulmonary cryptococcal infection of the right lung complicated with lung adenocarcinoma, including 3 years of follow-up, providing a reference for clinical practice.

Церебральный токсоплазмоз у ВИЧ-инфицированных пациентов в клинической практике

Cerebral toxoplasmosis is one of the most common opportunistic infections in HIV-infected patients. Neurological disorders in this group of patients require a differential diagnosis with demyelinating diseases, toxic damage to the nervous system, acute cerebrovascular accident and brain tumors. Cerebral toxoplasmosis can be accompanied by damage to internal organs and be combined with other secondary diseases in HIV-infected patients who are not aware of the presence of HIV-infection or hide this fact. Therefore, it becomes important to inform doctors of all specialties about features of clinical manifestations and the course of this pathology, which will allow early diagnosis and timely prescribing of effective therapy for the disease.

Characteristics of Pulmonary Tuberculosis patients with HIV in Regional General Hospital Dr Harjono Ponorogo period January 2018 – December 2022

Tuberculosis (TB) is the most common opportunistic infection in people living with HIV/AIDS in Indonesia, and HIV infection promotes Mycobacterium tuberculosis infection. In ODHIV, the probability of contracting TB is 10% per year. According to the Indonesian Ministry of Health, East Java is in second place with 71,909 cases and has the second highest number of AIDS patients and 824,000 TB cases in Indonesia. This study aims to determine the characteristics of pulmonary tuberculosis patients with HIV at DR Harjono Ponorogo Hospital for the period January 2018 - December 2022. This study applied descriptive research methodology with quantitative techniques with secondary data from medical records of pulmonary TB patients with HIV at Dr. Harjono Ponorogo Hospital for the period January 2018 - December 2022. The results showed a total sample of 130 medical records, there were several characteristics of TB patients with HIV, namely the highest age group of 30-39 years by 29.2%, more in male gender 73%. More patients had last high school education 38.5%, more treatment duration in patients who did for 9 months 61.5% and the results showed more patients with poor prognosis 56%. In conclusion, the characteristics of TB patients with HIV with the highest group at the age of 3-39 years, having male gender, more high school education, with more treatment duration of 9 months, and the results showed a poor prognosis.

Epidemiology of cryptococcal meningitis and fluconazole heteroresistance in Cryptococcus neoformans isolates from a teaching hospital in southwestern China.

Cryptococcal meningitis (CM), a common and serious opportunistic infection mostly caused by Cryptococcus neoformans, is primarily treated with fluconazole. Nevertheless, Cryptococcus neoformans strains that undergo repeated exposure to azoles can gradually acquire heteroresistance to fluconazole. The management of this specific CM infection poses a substantial challenge. Determining a globally accepted definition for fluconazole heteroresistance and developing effective and prompt methods for identifying heteroresistance is of utmost importance. We collected data on the clinical and epidemiological characteristics of patients diagnosed with CM. All the available Cryptococcus neoformans strains isolated from these patients were collected and subjected to antifungal susceptibility testing and evaluation of fluconazole heteroresistance. AIDS was present in 40.5% of the patients, whereas 24.1% did not have any underlying diseases. Patients with chronic diseases or impaired immune systems are susceptible to infection by Cryptococcus neoformans, a fungus that frequently (39.6%, 19/48) shows heteroresistance to fluconazole, as confirmed by population analysis profile (PAP).IMPORTANCEFluconazole heteroresistance poses a significant threat to the efficacy of fluconazole in treating cryptococcal meningitis (CM). Unfortunately, the standard broth microdilution method often misses the subtle percentages of subpopulations exhibiting heteroresistance. While the population analysis profile (PAP) method is esteemed as the gold standard, its time-consuming and labor-intensive nature makes it impractical for routine clinical use. In contrast, the Kirby-Bauer (KB) disk diffusion method offers a simple and effective screening solution. Our study highlights the value of KB over PAP and minimum inhibitory concentration (MIC) by demonstrating that when adjusting the inoculum concentration to 1.0 McFarland and subjecting samples to a 72-hour incubation period at 35°C, the KB method closely mirrors the outcomes of the PAP approach in detecting fluconazole heteroresistance. This optimization of the KB method not only enhances assay efficiency but also provides a blueprint for developing a timely and effective strategy for identifying heteroresistance.

Therapeutic potential of Garcinia kola against experimental toxoplasmosis in rats.

Cerebral toxoplasmosis, the most common opportunistic infection in immunocompromised individuals, is increasingly reported in immunocompetent individuals due to mutant strains of Toxoplasma gondii, which, furthermore, are reported to be resistant to available treatments. We assessed the therapeutic potential of Garcinia kola, a medicinal plant reported to have antiplasmodial and neuroprotective properties, against experimental toxoplasmosis in rats. Severe toxoplasmosis was induced in male Wistar rats (156.7 ± 4.1 g) by injecting them with 10 million tachyzoites in suspension in 500 µl of saline (intraperitoneal), and exclusive feeding with a low-protein diet [7% protein (weight by weight)]. Then, animals were treated with hexane, dichloromethane, and ethyl acetate fractions of Garcinia kola. Footprints were analysed and open-field and elevated plus maze ethological tests were performed when symptoms of severe disease were observed in the infected controls. After sacrifice, blood samples were processed for Giemsa staining, organs were processed for haematoxylin and eosin staining, and brains were processed for Nissl staining and cell counting. Compared with non-infected animals, the infected control animals had significantly lower body weights (30.27%↓, P = 0.001), higher body temperatures (P = 0.033) during the sacrifice, together with signs of cognitive impairment and neurologic deficits such as lower open-field arena centre entries (P < 0.001), elevated plus maze open-arm time (P = 0.029) and decreased stride lengths and step widths (P < 0.001), as well as neuronal loss in various brain areas. The ethyl acetate fraction of Garcinia kola prevented or mitigated most of these signs. Our data suggest that the ethyl acetate fraction of Garcinia kola has therapeutic potential against cerebral toxoplasmosis.

Real-World Safety and Effectiveness of Letermovir in Patients Undergoing Allogenic Hematopoietic Stem Cell Transplantation: Final Results of Post-Marketing Surveillance in Japan.

Cytomegalovirus (CMV) is a common opportunistic infection after allogenic hematopoietic stem cell transplantation (allo-HSCT). Letermovir, an inhibitor of CMV DNA terminase, is approved for CMV prophylaxis in allo-HSCT patients. We report the final results of post-marketing surveillance of letermovir in Japan. The case report forms were drafted in part by the Japanese Data Center for Hematopoietic Cell Transplantation using data elements in the Transplant Registry Unified Management Program and sent to individual HSCT centers to decrease the burden of reporting. Hematopoietic stem cell transplantation patients who received letermovir between May 2018 and May 2022 were registered. Data collected included physician-assessed adverse events/adverse drug reactions and clinical effectiveness (development of CMV disease, CMV antigen status, and use of preemptive therapy). A total of 821 HSCT patients were included in the safety analyses. Adverse drug reactions occurred in 11.33% of patients, with serious adverse drug reactions in 3.05%. The five most common adverse drug reactions were nausea (1.58%), renal impairment (1.46%), and acute graft versus host disease, CMV test positive, and hepatic function abnormal (0.61% each). A total of 670 patients were eligible for effectiveness analyses. Among these patients, 16.57% and 28.66% required preemptive therapy through week 14 and week 48, respectively. In addition, relatively few patients developed CMV disease throughout the follow-up period (1.34% at week 14 and 3.85% at week 48). This final analysis of post-marketing surveillance with up to 48 weeks follow-up period in Japan provides further evidence supporting the safety profile and effectiveness of letermovir for CMV prophylaxis in patients undergoing allo-HSCT in real-world settings.

Imaging of Central Nervous System Infections in the Immunocompromised Patient

Immunocompromised patients are susceptible to the same infections as immunocompetent individuals and have an additional unique risk for atypical infections in the central nervous system (CNS). Many CNS infections carry a poor prognosis if not treated promptly, so it is prudent for radiologists to recognize key findings and have a high level of suspicion in immunocompromised patients. Moreover, a patient may have no known deficiency but can present with an atypical CNS infection as their first sign of an immunocompromised state, thus allowing the radiologist to be the first to suggest specific workup such as HIV testing. Because different infection sources (bacterial, fungal, and parasitic) have separate treatments, it is highly valuable to guide management in the right direction early in the diagnostic workup. This article discusses common opportunistic infections observed in the immunocompromised patient, primarily focusing on neuroimaging findings and pertinent clinical background and treatment for each disease entity. This article also emphasizes the importance of familiarity with the differential diagnosis for ring-enhancing lesions within the CNS.

Hospitalizations for opportunistic infections following transplantation and associated risk factors: A national cohort study of Medicare beneficiaries.

Opportunistic infections (OIs) are a significant cause of morbidity and mortality after organ transplantation, though data in the liver transplant (LT) population are limited. We performed a retrospective cohort study of LT recipients between January 1, 2007 and Deceber 31, 2016 using Medicare claims data linked to the Organ Procurement and Transplantation Network database. Multivariable Cox regression models evaluated factors independently associated with hospitalizations for early (≤1year post transplant) and late (>1year) OIs, with a particular focus on immunosuppression. There were 11320 LT recipients included in the study, of which 13.2% had at least one OI hospitalization during follow-up. Of the 2638 OI hospitalizations, 61.9% were early post-LT. Cytomegalovirus was the most common OI (45.4% overall), although relative frequency decreased after the first year (25.3%). Neither induction or maintenance immunosuppression were associated with early OI hospitalization (all p>.05). The highest risk of early OI was seen with primary sclerosing cholangitis (aHR 1.74; p =.003 overall). Steroid-based and mechanistic target of rapamycin inhibitor-based immunosuppression at 1year post LT were independently associated with increased late OI (p<.001 overall). This study found OI hospitalizations to be relatively common among LT recipients and frequently occur later than previously reported. Immunosuppression regimen may be an important modifiable risk factor for late OIs.

Characteristics of Immunological Non-Responders in People Living with HIV at Abepura Hospital Papua

Infection of Human Immunodeficiency Virus (HIV) lowers the body's immune system, especially CD4+ cells, making it more susceptible to opportunistic infections. Approximately 10-40% of People Living with HIV/AIDS (PLHIV) fail to achieve normal levels of CD4+ T cells despite continued virological suppression, a condition called Immunological Non-Responders (INR). Previous studies have shown that INR is considered a predictor of disease progression in people with HIV receiving antiretroviral (ARV)s through various mechanisms of suppression of the immune system that increases morbidity and mortality. Papua is an HIV epidemic area with a prevalence of 2.3%. This research is a cohort study conducted at Abepura Hospital from June 2019 to February 2023, which aims to identify the factors that influence the occurrence of INR in PLHIV receiving ARV therapy. There were 123 research subjects consisting of 55 people (44.7%) in the INR group and 68 people (55.3%) in the non-INR group. The results showed that the incidence of INR was higher in males than females (p=0.019), INR was significantly associated with increasing age (p=0.013), and CD4 count was low at the start of ARVs (p=0.002). There was a significant difference in CD4 counts between INR and non-INR (p&lt;0.001). Oral candidiasis as a common opportunistic infection is more common in people with INR than in non-INR. (p=0.037). This study suggested that it is necessary to carry out a CD4 examination at the start of therapy and monitoring every 6 months to detect possible INR to prevent an increased risk of AIDS and non-AIDS, which increases mortality.

Pathogenetic parallels and clinical relationships of HIV infection and Hodgkin’s lymphoma

Aim: to show the importance of the features of the development of Hodgkin’s lymphoma (HL) against the background of HIV infection, possible clinical relationships and consequences of simultaneous diseases in patients, as well as complex therapy. Material and methods. The article presents an analytical review of the problem and retrospective data on 63 patients with HIV[1]associated HL (HIV-HL) who were diagnosed with HL in St. Petersburg hospitals in the period 2000–2017. For the diagnosis of HIV-HL, regulated morphological, immunohistochemical, instrumental and laboratory research methods were used, the tumor stage was determined based on the Cotswolds-modified Ann Arbor classification. The diagnosis of HIV infection was confirmed by the detection of specific antibodies to HIV (and the p24 antigen) during serological and enzyme immunoassay of blood, by immune blotting. The number of copies of HIV RNA and the number of CD4 lymphocytes in the blood of patients were determined using commercial test systems approved for use in the territory of the Russian Federation. The analysis of overall survival was performed using the Kaplan–Meyer method. Statistical processing of the research results was performed using statistical programs MS Excel 2010, GraphPad Prism 8 (GraphPad Software, Inc., USA), SPSS version 22.Results. The study group was dominated by men (73%), the median age was 32 years, in 16 (25.4%) patients HIV and HL were detected simultaneously. The number of CD4 lymphocytes &gt; 500 cl/μl at the HL debut was noted in 33.3% of patients, patients with severe immunosuppression prevailed (50–250 cl/μl in 20 (31.7%), 250–500 cl/μl in 11 (17.5%), less than 50 cl/μl in 11 (17.5%). The amount of HIV RNA&gt;400 kop/ml was noted in 82.5%, HIV infection at stages 4B-5 was detected in 89% of cases, at the time of detection of HL ART was performed in 16 patients. EBV coinfection (77.8%), cytomegalovirus (60%), viral hepatitis (55.6%) with a predominance of viral hepatitis C, common opportunistic infections (tuberculosis, pneumocystis pneumonia, toxoplasmosis of the brain, common candidiasis), simultaneously occurring from 1 to 3 infections were observed in 77.8%. Stage IV HL was established in 54%, III — in 22%, II — in 24% of patients, the presence of B-symptoms was confirmed in 73% of cases. The predominant histological variant of HIV-HL was nodular sclerosis (58 patients), mixed[1]cell sclerosis in 4 patients, with lymphoid predominance in 1 case. Extranodal lesions were observed in 34 (54%), complications of the tumor process in 33 (37.5%) patients. 42 (66.7%) patients received antitumor treatment for HL: line 1 according to the ABVD scheme — 85.7% (80% achieved PET-negative complete remission (CR), according to the VEASORR esc or VEASORR schemes — 33.3%; line 2 — according to the ICE or DHAP schemes (n=10). An objective response was noted in 4 patients, PET-negative response in 2 of them, partial PET-positive regression in 2 patients. Progression was observed in 2 people. Autologous bone marrow transplantation was performed in 2 patients (in partial PET-positive regression); line 3 (n=3) — chemoimmunotherapy with bendamustine, gemcitabine (2 patients underwent autologous bone marrow transplantation). The cumulative life expectancy of patients for 1 year and 2 years was 44% and 37%, respectively, 1-year overall survival was 75%, 2-year — 60%. The factors negatively affecting survival and life expectancy were tumor progression and complications, ECOG≥2 (p=0.0001), candidiasis, pneumonia (p=0.001), viral hepatitis B and C (p=0.045), lack of antitumor treatment and ART (p=0.0001), age younger than 40 years, central nervous system damage, the presence of 1 or more concomitant infections (p=0.024). Conclusion. HIV-HL is one of the most common hematological malignancies, characterized by heterogeneity in its manifestations, polymorphism of pathogenetic and clinical features and relationships. During the dispensary supervision of PLHIV, special attention should be paid to the factors of an unfavorable prognosis of the disease, the timeliness of the appointment of ART and the assessment of the risks of developing lymphoproliferative diseases within the framework of the immune system restoration syndrome (IRIS) in order to increase their survival and quality of life. Further research is needed on the pathogenesis, early diagnosis and effective treatment of lymphomas associated with the human immunodeficiency virus

Transcriptional signature of durable effector T cells elicited by a replication defective HCMV vaccine.

Human cytomegalovirus (HCMV) is a leading infectious cause of birth defects and the most common opportunistic infection that causes life-threatening diseases post-transplantation; however, an effective vaccine remains elusive. V160 is a live-attenuated replication defective HCMV vaccine that showed a 42.4% efficacy against primary HCMV infection among seronegative women in a phase 2b clinical trial. Here, we integrated the multicolor flow cytometry, longitudinal T cell receptor (TCR) sequencing, and single-cell RNA/TCR sequencing approaches to characterize the magnitude, phenotype, and functional quality of human T cell responses to V160. We demonstrated that V160 de novo induces IE-1 and pp65 specific durable polyfunctional effector CD8 T cells that are comparable to those induced by natural HCMV infection. We identified a variety of V160-responsive T cell clones which exhibit distinctive "transient" and "durable" expansion kinetics, and revealed a transcriptional signature that marks durable CD8 T cells post-vaccination. Our study enhances the understanding of human T-cell immune responses to V160 vaccination.

Advances in Antiretroviral Therapy for Patients with Human Immunodeficiency Virus-Associated Tuberculosis.

Tuberculosis is one of the most common opportunistic infections and a prominent cause of death in patients with human immunodeficiency virus (HIV) infection, in spite of near-universal access to antiretroviral therapy (ART) and tuberculosis preventive therapy. For patients with active tuberculosis but not yet receiving ART, starting ART after anti-tuberculosis treatment can complicate clinical management due to drug toxicities, drug-drug interactions and immune reconstitution inflammatory syndrome (IRIS) events. The timing of ART initiation has a crucial impact on treatment outcomes, especially for patients with tuberculous meningitis. The principles of ART in patients with HIV-associated tuberculosis are specific and relatively complex in comparison to patients with other opportunistic infections or cancers. In this review, we summarize the current progress in the timing of ART initiation, ART regimens, drug-drug interactions between anti-tuberculosis and antiretroviral agents, and IRIS.