Human Immunodeficiency Virus Tuberculosis Research Articles

Differential Epigenetic Regulation in Uninfected and Tuberculosis-Human Immunodeficiency Virus Co-Infected Patients.

This study aimed to compare the degree of epigenetic modifications between a TB-HIV co-infected cohort and uninfected subjects. Formalin-fixed paraffin-embedded (FFPE) tissues were retrieved from 45 TB-HIV co-infected and 45 control individuals. Real-time PCR was applied to compare the level of expression of genes involved in epigenetic regulation. The protein multiplex assay was used to assess the degree of protein modification. DNA sequencing was used to determine the evolutionary relationships between the infecting HIV and Mtb strains. Our results indicated a significant increase in the expression of the five candidate genes in the patients with TB-HIV relative to the control cohort. A sharp increase in the degree of histone methylation, acetylation and phosphorylation was observed in TB-HIV co-infected patients. The phylogenetic analysis classified the strains into three distinct HIV clusters and five Mtb clusters. The disparities in the expression profiles of our candidate genes between the TB-HIV cohort and non-TB-HIV group highlights the important role played by various TB and HIV strains in regulating the host gene expression landscape.

Dynamics of Matricellular Protein Levels in Blood Predict Recovery in Patients with Human Immunodeficiency Virus-Tuberculosis Coinfection.

Chronic immune activation in tuberculosis (TB) associated with human immunodeficiency virus (HIV) infection (HIV/TB) modifies their clinical course. We prospectively measured osteopontin (OPN), full-length galectin-9 (FL-Gal9), and total-Gal9 (T-Gal9) levels in 32 patients with HIV/TB coinfection treated with anti-tuberculosis and antiretroviral therapies over 6-18 months to determine the amelioration of inflammatory conditions in response to the therapies. We observed a significant time-dependent decrease in FL-Gal9 in both pulmonary TB (PTB, n = 20) and extrapulmonary TB (EPTB, n = 12) patients. The levels of T-Gal9, OPN, and CRP decreased significantly after treatment in only PTB patients. We calculated the inflammatory score (INS) indicating immunologic recovery based on the decline in OPN, FL-Gal9, T-Gal9, and CRP levels. Baseline levels of T-Gal9 and OPN positively correlated with INS in all TB and only PTB patients, respectively, indicating that their levels predict better recovery. In contrast, FL-Gal9 levels at the second visit negatively correlated with INS in EPTB patients. The decrease rate in OPN levels at the second visit also correlated positively with INS in PTB patients. Women showed a higher INS and lower levels of FL-Gal9 than men. The patients with moderate grade severity on chest X-ray had higher CD4 cell numbers than those with limited grade severity. Monitoring these markers will help to predict and assess the response to therapy as well as to devise strategies to reduce the complications caused by chronic immune activation in patients with HIV/TB coinfection.

What is New in the Diagnosis of Childhood Tuberculosis?

The fact that almost half of the 1 million cases of childhood tuberculosis (TB)globally remain undiagnosed jeopardizes the TB elimination goal. Fortunately, there are new advances in this fieldwhich have the potential to bridge this diagnostic gap. Advances in imaging include computer assisted interpretation of chest X-rays (CXRs), point of care ultrasound (POCUS) and faster and superior computed tomography/ magnetic resonance imaging (CT/ MRI) protocols. The urine lipoarabinomannan test has proved to be a good point of care test for diagnosing TB in Human immunodeficiency virus (HIV) infected children. Stool and nasopharyngeal aspirates are emerging as acceptable alternatives for gastric lavage and induced sputum for diagnosing intrathoracic tuberculosis. Xpert MTB/RIF Ultra has improved sensitivitycompared to Xpert MTB/RIF for diagnosing both pulmonary/ extrapulmonary TB. Xpert XDR is another commercially available accurate point of care test for detecting resistance to drugs other than rifampicin in smear positive samples. Other molecular methods including new line probe assays, pyrosequencing, whole genome sequencing, and targeted next generation sequencing are extremely promising but not available commercially at present. The C-Tb skin test isan acceptable alternative to the tuberculin skin test and interferon gamma release assays for diagnosis of latent infection. There is an urgent need to incorporate some of these advances in the existingdiagnostic algorithms of childhood TB.

Surviving a Triple Coinfection in an HIV Patient: Tuberculosis Histoplasmosis and SARS-CoV-2: Case Report

BACKGROUND: Antiretroviral therapy has become the key to global control of the HIV/AIDS pandemic. The human immunodeficiency virus (HIV) is a retrovirus that attacks CD4+ T lymphocytes. AIDS is defined by a CD4+ count of less than 200 cells/mm³, as well as the appearance of opportunistic infections, which are the main cause of death in these patients. The most common types of co-infections are Mycobacterium tuberculosis, hepatitis C virus, Cryptococcus neoformans, Plasmodium falciparum, and hepatitis B virus. The incidence of certain opportunistic infections will continue to be a problem, especially in developing countries where access to antiretroviral therapy remains limited. THE CASE: A 27-year-old male patient from Juticalpa, Olancho, with a history of HIV/AIDS C3 diagnosed on January 23, 2022, with a CD4+ lymphocyte count of 115 cells/microliters and a viral load of 10,000 copies/ml, goes to his health center from his department with a history of fever, intermittent type, quantified at 40 Celsius, predominantly nocturnal, attenuated with acetaminophen, without exacerbations. Among its accompanying symptoms, general malaise and fatigue, he received treatment of which the patient is unaware. Five days after his last visit, the patient returned in poor hemodynamic condition, dehydrated, with persistent fevers of 40 Celsius and respiratory difficulty, for which fluid therapy and oxygen were started. Antigen for SARS-COV-2 is requested with a positive result, for which the patient is transferred to Tegucigalpa to the Instituto Nacional Cardiopulmonar del Torax a third level hospital. Upon admission to our hospital, hemodynamically unstable, Glasgow 14/15, it was decided to perform GENXPERT, sputum and antigen for histoplasmosis and tuberculosis, which were both positive. It was decided to transfer the patient to the intensive care unit, where he received treatment with isoniazid 300 mg orally, rifampicin 600 mg orally, ethambutol 1200 mg Monday, Wednesday and Friday, and pyridoxine 50 mg orally. Likewise, liposomal amphotericin B 280 mg was administered. Twenty days later, the patient was stable after extubating. He was transferred to a respiratory isolation room to receive treatment for COVID-19 and pulmonary tuberculosis. CONCLUSION: Co-infections between HIV and COVID-19 and tuberculosis with COVID-19 are currently poorly known. To date, only six cases of triple co-infections in HIV patients have been reported worldwide in Panama, the United States, Brazil and Cameroon. Due to the great clinical similarity, an in-depth differential diagnosis should be made between COVID-19 and tuberculosis. Timely diagnosis and treatment improve patient survival rates.

Global prevalence, burden and trend in HIV and drug-susceptible tuberculosis co-infection from 1990 to 2019 and prediction to 2040

ObjectivesThe purpose of this study is to describe the current situation and forecast the trends of co-infection between the human immunodeficiency virus (HIV) and drug-susceptible tuberculosis (DS-TB) in different countries, across various age groups and genders. MethodsWe obtained data on the number of cases, age-standardized incidence rate, age-standardized prevalence rate, age-standardized rate of disability-adjusted life years (DALYs), and age-standardized death rate from the Global Burden of Disease (GBD) 2019 database. These data were used to describe the distribution and burden of co-infection between the human immunodeficiency virus (HIV) and DS-TB in different regions, genders, and age groups. We employed joinpoint regression analysis to analyze the temporal trends from 1990 to 2019. Additionally, an age-period-cohort model was established to forecast the future trends of co-infection up to 2040. ResultsThe prevalence and burden of co-infection varied across different age groups and genders. The territories with the higher disease burden were distributed in some Asian and African countries. In terms of temporal trends, the age-standardized incidence rate and age-standardized prevalence rate of HIV and DS-TB co-infection exhibited an overall increasing trend from 1990 to 2019, and the prediction indicated a slow downward trend from 2019 to 2040. ConclusionsThe co-infection of HIV and DS-TB posed a grave threat to public health and economic development. What’s more, there existed a significant disparity between the actual state of co-infection and the desired goals for prevention and control.

Tuberculosis and HIV co-infection among miners at selected mining sites in Migori County, Kenya

Tuberculosis (TB) disease is caused by acid-fast bacilli called Mycobacterium tuberculosis. The emergence of drug-resistant TB variants as well as co-infection with the Human Immunodeficiency Virus (HIV) have complicated treatment for TB. Kenya currently implements TB screening and HIV testing for all patients and their caretakers, regardless of their reason for visiting the hospitals. Drug resistance is tested in all HIV-positive TB suspects to guide the choice of drugs in cases of TB-HIV co-infection and minimise delays in treatment initiation. These services are, however, confined to the health facilities, and all those who do not visit the hospitals are missed. The objective of our study was to evaluate TB missed opportunities among the mining community of Osiri-Matanda gold mines in Nyatike sub-county, Migori County, Kenya. Community health outreaches were conducted in collaboration with the Ministry of Health. Demographic information was recorded for all clients consenting to the study. HIV testing was done using the HIV rapid testing kits. Sputum samples were tested in the local laboratory using Ziel-Neelsen (ZN) staining. All TB-positive outcomes were further tested using GeneXpert MTB/RIF to determine whether or not they were resistant to Rifampicin. A total of 297 participants were enrolled in the study. Among these, 49.5% were males and 50.5% were females. The youngest participant was 15 years old, while the oldest was 63 years old. A 15.5% TB prevalence was found after testing, with the age range of 35–44 having the highest prevalence at 39%. 71.7% of TB infections were male, while 28.3% were female. HIV-TB co-infections accounted for 37% of cases. None of the TB cases were RIF-resistant. This data shows that males are more at risk of TB and HIV infections than females. Collaborative health outreaches that include screening and testing for both TB and HIV could help in early detection and minimise missed opportunities.

Impact of COVID-19 pandemic on Tuberculosis and HIV services in Ghana: An interrupted time series analysis.

The Coronavirus disease 2019 (COVID-19) burden, coupled with unprecedented control measures including physical distancing, travel bans, and lockdowns of cities, implemented to stop the spread of the virus, have undoubtedly far-reaching aftereffects on other diseases. In low and middle-income countries (LMICs), a particular worry is the potential impact on Human Immunodeficiency Virus (HIV) and Tuberculosis (TB), as a consequence of possible disruption to health services and limiting access to needed life-saving health care. In Ghana, there is a paucity of information regarding the impact of COVID-19 on disease control, particularly TB and HIV control. This study sought to contribute to bridging this knowledge gap. The study involved the analysis of secondary data obtained from the District Health Information Management System-2 (DHIMS-2) database of Ghana Health Service, from 2016 to 2020. Data were analysed using an interrupted time-series regression approach to estimate the impact of COVID-19 on TB case notification, HIV testing, and Antiretroviral Therapy (ART) initiations, using March 2020 as the event period. The study showed that during the COVID-19 pandemic period, there was an abrupt decline of 20.5% (955CI: 16.0%, 24.5%) in TB case notifications in April and 32.7% (95%CI: 28.8%, 39.1%) in May 2020, with a median monthly decline of 21.4% from April-December 2020. A cumulative loss of 2,128 (20%; 95%CI: 13.3%, 26.7%) TB cases was observed nationwide as of December 2020. There was also a 40.3% decrease in people presenting for HIV tests in the first month of COVID-19 (April 2020) and a cumulative loss of 262620 (26.5%) HIV tests as of December 2020 attributable to the COVID-19 pandemic. ART initiations increased by 39.2% in the first month and thereafter decreased by an average of 10% per month from May to September 2020. Cumulatively, 443 (1.9%) more of the people living with HIV initiated ART during the pandemic period, however, this was not statistically significant. This study demonstrated that the COVID-19 pandemic negatively impacted TB case notifications and HIV testing and counselling services, However, ART initiation was generally not impacted during the first year of the pandemic. Proactive approaches aimed at actively finding the thousands of individuals with TB who were missed in 2020 and increasing HIV testing and counselling and subsequent treatment initiations should be prioritised.

Evaluation of Nutritional Care for HIV (Human Immunodeficiency Virus) Patients with Pulmonary Tuberkulosis

Introduction: Indonesia is one of the countries with the fastest HIV development in Asia. The cumulative number of cases from 2003 to 2013 was 108,600 cases. The national accumulation is estimated at 186,000 people living with HIV in 2010. Papua is an area with an expanding HIV prevalence of 2.4%. HIV (Human Immunodeficiency Virus) is a virus that attacks the body's immune system. Tuberculosis (TB) is a bacterial infection that is spread through droplets inhaled from the coughs or sneezes of an infected person. Nutritional status is an important factor of disease immunity and plays a role in the frequency and severity of infection by inhibiting immune function for HIV patients with pulmonary TB. Vulnerability in HIV patients with a nutritional status below normal is more easily infected with Mycobacterium tuberculosis. Based on cases of TB HIV coinfection during 2010-2017, there was an increase from 2,393 to 7,796. This study aimed to determine the enhancement of nutritional needs of patients during hospitalization.Method: This research method uses a descriptive case study. This research was conducted in July 2021 at the Rumah Sakit Umum Tangerang with a saturated sample.Result: The outcome of observations and interviews with nutritional care for five days, there was an improvement in appetite disorders with an initial fulfillment of 70% to achieve a nutritional intake of 100%, the feeding route with the NGT gradually became oral, as well as the texture of enteral food, then the texture of the combination of soft and enteral, thus regular enteral meals. The finding is that monitoring the compliance of nutrients gradually increase the need for daily intake, eating routes, and evolved eating texture.

Varied trends of tuberculosis and HIV dual epidemics among different countries during 2000–2020: lessons from an ecological time-trend study of 9 countries

Background While Human Immunodeficiency Virus (HIV) infection is a well-established risk factor for tuberculosis (TB), the effect of HIV infection on TB incidence varies across countries given differences in local epidemiological factors and disparate progress with respect to TB elimination goals. Methods In this descriptive epidemiological study, we explored the country-specific associations between HIV prevalence and TB incidence in nine countries representing four WHO regions using data between 2000 and 2020. For each of these countries, we (1) described the trends of TB incidence and HIV prevalence, and (2) examined country-level associations between TB incidence and HIV prevalence, using negative binomial regression. Results The trends of TB incidence and HIV prevalence, and the country-level associations, varied across the study countries. Angola, Thailand and Zimbabwe showed parallel TB incidence and HIV prevalence trends while the two trends diverged in Brazil, Liberia and Indonesia during the study period. Additionally, the strength of association between HIV prevalence and TB incidence varied widely between countries, with the risk ratio ranging from 0.42 (95% CI: 0.36, 0.49) in Indonesia to 2.78 (95% CI: 2.57, 3.02) in Thailand. Conclusions The association of HIV infection with TB incidence varied across high burden settings, suggesting that HIV is not a ubiquitous driver of TB incidence. Without acknowledging the local drivers of TB epidemics across countries, the END TB Strategy cannot be adapted at the country level. The findings from this analysis can inform the design of future studies to identify country-specific drivers of TB using individual-level data.

Assessing Influence of HIV Status on Management outcomes of Drug Sensitive Pulmonary Tuberculosis in the Bo District of Southern Sierra Leone.

Purpose: Tuberculosis in Human immunodeficiency virus is a predictor of unfavourable outcome during the management of TB cases due to the synergy both bear in the patient. This study is to test the hypothesis that patient is more likely to be unfavourable in the co infected than the TB stand-alone patients with standard treatment in patients. The associated factors might not be exhaustive that leads to outcomes factored in the study.
 Methodology: The retrospective cohort study data of 1,947 patients admitted from 1st January 2020 to 1st January 2022 at TB treatment centres in Bo district of Sierra Leone was analysed using datatab software after data completeness was checked and cleaned. Both bi-variable and multi-variable logistics regression and other statistical methods were employed to assess the relationship between HIV+TB synergic as well as TB alone outcomes. Data was analysed based on 95% CI and p<0.05.
 Findings: When an ANOVA was used to test for significance from zero, F=3.41, p = 0.002, R2 = 0.01. Regression coefficients for exits = 1.17 - 0.02., gender =-0.02, literacy = -0.1, family bread winner with TB= -0.02 and foods insecurity = +0.07. A point-biserial correlation was also computed to determine the relationship between HIV status and TB interms of outcome which showed a positive correlation between HIV status and exit code information, although no statistically significance (rpb = 0.04, n = 1987, p = .065).
 Unique contribution to theory, practice and policy: Successful treatment outcome was high among HIV/TB co-infected as well as TB mono-infected should both be treated with standard treatments. Strengthening patient management in a collaborative approach and use of novel drugs as well as research will increase the survival rate of patients treated. With standard treatment and patient centered care the outcome of TB patient management will not be hinged on their HIV status. The adoption of this theory into policy in TB programmes will improve the success rate in TB management.

A Review of the Development of Multitarget Molecules against HIV-TB Coinfection Pathogens.

The human immunodeficiency virus (HIV) produces the pathologic basis of acquired immunodeficiency syndrome (AIDS). An increase in the viral load in the body leads to a decline in the number of T lymphocytes, compromising the patient's immune system. Some opportunistic diseases may result, such as tuberculosis (TB), which is the most common in seropositive patients. Long-term treatment is required for HIV-TB coinfection, and cocktails of drugs for both diseases are used concomitantly. The most challenging aspects of treatment are the occurrence of drug interactions, overlapping toxicity, no adherence to treatment and cases of resistance. Recent approaches have involved using molecules that can act synergistically on two or more distinct targets. The development of multitarget molecules could overcome the disadvantages of the therapies used to treat HIV-TB coinfection. This report is the first review on using molecules with activities against HIV and Mycobacterium tuberculosis (MTB) for molecular hybridization and multitarget strategies. Here, we discuss the importance and development of multiple targets as a means of improving adherence to therapy in cases of the coexistence of these pathologies. In this context, several studies on the development of structural entities to treat HIV-TB simultaneously are discussed.

Leukotriene A4 hydrolase (LTA4H rs17525495) gene polymorphisms and paradoxical reactions in extrapulmonary tuberculosis

Paradoxical reactions (PRs) are poorly studied complex immunological phenomena, among patients with tuberculosis (TB). When PRs involves critical structures like the central nervous system (CNS), immunomodulatory therapy is often required. Predictors for PRs in TB to pre-empt appropriate treatment strategies in high-risk groups are lacking. TT genotype of Leukotriene A4 hydrolase (LTA4H) promoter region rs17525495 polymorphisms are associated with exaggerated immune responses in Tuberculous meningitis (TBM), the most severe form of extrapulmonary tuberculosis (EPTB). The association of these polymorphisms with PRs is not known. We evaluated this plausibility among 113 patients with EPTB, at high risk of PRs. Majority [81 (71.7%)] had disseminated tuberculosis with prominent CNS [54 (47.8%)] and lymph node involvement [47 (41.6%)]. Human immunodeficiency Virus (HIV) co-infection was seen among 23 (20.3%) patients. PRs were noted in 38.9% patients, at a median duration of 3 months (IQR 2–4). LTA4H rs17525495 single nucleotide polymorphism (SNP) analysis showed 52 (46%) patients had CC, 43 (38.1%) had CT and 18 (15.9%) had TT genotypes. There was no statistically significant difference in occurrence [CC 38.5% vs CT 39.5% vs TT 38.7%] and time of onset [median (IQR)] of PRs across the genotypes [CC 3 (1–4.7), CT 3 (2–5), TT 2 (2–3)]. PRs was shown to be significantly linked with HIV co-infection (RR 0.6, 95% CI 0.29–1.28), culture positivity (RR 0.5, 95% CI 0.28–1.14), TB Lymphadenitis (RR 0.7, 95% CI 0.44–1.19) and CNS involvement RR 2.1, 95% CI 1.27–3.49) in the univariate analysis (p < 0.2). On multivariate analysis, CNS involvement alone was associated with PRs (aRR 3.8 (1.38–10.92); p < 0.01). PRs were associated with CNS involvement but not with LTA4H rs17525495 polymorphisms.

Evaluation of the impact of COVID-19 in people coinfected with HIV and/or tuberculosis in low-income countries: study protocol for mixed methods research in Burkina Faso

BackgroundAn issue of particular concern is the impact of the 2019 novel coronavirus (2019 nCOV) on the people coinfected with the Human Immuno-deficiency Virus (HIV) and/or tuberculosis (TB). Unfortunately, this interaction has not been well explored in African despite the large proportion of these risk populations living with HIV and/or patients and/or tuberculosis (TB) in the African region. This study aims to design a research protocol for assessment of the impact of coronavirus disease 2019 (COVID-19) on these risk populations in response to COVID-19 strategic plans in Burkina Faso by generating serological, epidemiological, virological, clinical and socio-anthropological evidence-based data.MethodsA multidisciplinary research will be conducted in the city of Bobo-Dioulasso, Burkina Faso using mixed methods. Data will be collected from a cohort of people living with HIV and/or TB patients in the city (i) to determine the proportion of people with specific antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using retrospective data ; (ii) to determine the proportion of people infected with Covid-19 and the dynamics of viral loads and antibodies in these people based on prospective data; (iii) to identify circulating SARS-COV-2 variants and novel biomarkers using prospective data ; (iv) to analyze perceptions, community experiences and response strategies during the public health emergencies imposed by COVID-19 through a qualitative study.DiscussionThis study will generate factual and comprehensive data that will contribute in improving response strategies to COVID-19 and the other possible emerging diseases with keen interest on the risk populations living with HIV and/or TB infected patients.

Clinico-epidemiological Determinants of Tuberculosis Co-infection among Adults Attending an Antiretroviral Centre at a Tertiary Care Hospital in Madhya Pradesh

Background: The co-infection of human immunodeficiency virus-tuberculosis (HIV-TB) is a serious public health concern and aptly called the ‘deadly duo’. Recognising the determinants of the co-infection will help target the vulnerable population for prevention and reduce mortality. Aims: The objective of this study was to estimate the proportion of HIV-TB co-infection among adults attending the antiretroviral therapy (ART) centre at a tertiary healthcare facility and associated clinico-epidemiological determinants. Patients and Methods: A cross-sectional analytical research that lasted for 6 months was conducted at the ART Centre of Medical College, Gwalior, Madhya Pradesh. According to the inclusion criteria, 251 newly diagnosed HIV patients were enrolled in the study. The pro forma administered by the interviewer was utilised to collect the socio-demographic information at the time of enrolment by face-to-face interviews. To gather the clinical details, records were reviewed. A Chi-square test of significance was used to determine the difference between proportions after descriptive analysis. Variables found significant in bivariate analysis were put in multivariate logistic regression to predict HIV-TB co-infection. The odds ratio was estimated at 95% confidence interval (CI). Results: Among the participants, 27.5% of the 251 people had both TB and HIV. Males who were employed as labourers (X 2 = 25.5, df = 4 and P = 0.001) were epidemiologically more likely to get co-infection. In comparison to the other group of HIV-only patients, the CD4+ count of co-infected individuals was considerably lower (X 2 = 6.37, df = 3 and P &lt; 0.01). Clinical staging of HIV (adjusted odds ratio [aOR] =4.70, 95% CI 2.34–9.43; P = 0.001), body mass index (aOR = 0.46, 95% CI 0.013; P = 0.25–0.85) and CD4+ count (aOR = 0.22, 95% CI 0.08–0.60; P = 0.003) were found to predict HIV-TB co-infection among people living with HIV (PLHIV). Conclusion: The study concludes, being underweight with an advanced clinical staging (World Health Organisation Clinical Stage III or IV of HIV) and a CD4+ count equal to or below 300 cells/μL increase the vulnerability of HIV-TB co-infection among adult PLHIV.

Characterization of peripheral cytokine-secreting cells responses in HIV/TB co-infection.

Currently the responses of peripheral cytokine-secreting cells in the natural course of human immunodeficiency virus (HIV) and tuberculosis (TB) co-infection haven't been fully elucidated. The function of peripheral proinflammatory, regulatory and cytotoxic cytokine-secreting cells were investigated by direct intracellular cytokine staining (ICS) and flow cytometry, additionally, the absolute numbers of different cytokine-secreting cells were measured among patients with HIV/TB co-infection (HT group), and compared them with the healthy controls (HC group), patients with TB (TB group) and patients with HIV infection (HIV group). After one week's anti-TB treatment, the changes of the percentages of cytokine-secreting cells were further evaluated in TB and HT groups. Totally 26 individuals in the HC group, 51 in the TB group, 26 in the HIV group and 29 in the HT group were enrolled. The HT. HT group exhibited significantly lower absolute numbers of IFN-γ+CD4+, IFN-γ+CD8+, TNF-α+CD4+, IL17A+CD4+ T cells and TNF-α+CD14+ monocytes than the TB and HIV groups. Compared with the TB group, the percentages of CD8+ T cells secreting IFN-γ and perforin (p=0.010; p=0.043) were significantly lower among the HT group. Compared with the HIV group, the percentages of CD4+, CD8+ T cells and CD14+ monocytes secreting TNF-α (p=0.013; p=0.001; p<0.001) were significantly decreased, and the percentage of CD8+ T cells secreting IL-17A (p=0.015) was significantly increased among the HT group. Both the percentages of CD4+ T cells secreting TGF-β (p<0.001; p=0.001), and CD4+ and CD8+ T cells secreting granzyme A (all p<0.001), were significantly higher among the HT group than among the TB group and HIV group. After one week's anti-TB treatment, an increased percentage of CD4+ T cells secreting TNF-α (p=0.003) was found in the TB group, and an increased percentage of CD8+ T cells secreting TNF-α (p=0.029) was found in the HT group. Significantly different functional profiles of peripheral proinflammatory, regulatory, and cytotoxic cytokine-secreting cells were observed in the natural course of HIV/TB co-infection compared to TB and HIV infection alone, even though the absolute numbers of those cells were significantly lower in HIV/TB co-infection. TNF-α-secreting CD8+ T cells may be a more sensitive marker for early evaluation of anti-TB treatment efficacy in patients with HIV/TB co-infection.

High Positivity Rate of Urinary Mycobacterium tuberculosis Antigens Cocktail (ESAT-6, CFP-10, and MPT-64) in Active Tuberculosis Patients With and Without Human Immunodeficiency Virus Infection: A Cross-Sectional Study.

Human immunodeficiency virus (HIV) infection is a risk factor for the occurrence of a large of Mycobacterium tuberculosis (Mtb) antigen load in the body. The antigens cocktail namely early secretory antigenic target protein 6-kDa (ESAT-6), Culture filtrate protein 10 kDa (CFP-10), and Mycobacterium tuberculosis protein 64 (MPT-64) are secreted by Mtb during replication, hence, their concentration increase in patients with active Tuberculosis (TB). This increased levels facilitates their entry into the systemic circulation, followed by secretion by the glomerulus into the urine. The aim of this study was to determine the positivity rate of the urinary Mtb antigens cocktail between TB patients with and without HIV infection. This is an observational descriptive comparative study conducted with a cross-sectional design. Random urine samples were collected from patients diagnosed with active TB in Dr. Hasan Sadikin Bandung Hospital in 2021. The subjects were divided into 2 groups, TB-HIV group and TB without HIV group. The samples were tested using the quantitative immunochromatography method. Sixty active TB patients consisting of TB patients with HIV infection (n = 30) and TB patients without HIV infection (n = 30). The positivity in the urinary Mtb antigens cocktail was 93.3% for TB-HIV group and 100% for TB without HIV group (P = .492). The median concentration of urinary Mtb antigens cocktail in TB patients without HIV infection was higher than that of TB patients with HIV infection (137.73 ng/mL vs 96.69 ng/mL, respectively; P = .001). There was no significant difference in the positivity rate, meanwhile, there was a significant difference in concentration of the urinary Mtb antigens cocktail between active TB patients with and without HIV infection. Interestingly, this urinary Mtb antigens cocktail can be found in both groups without being affected by the patient's immune condition, thus becoming a test to assist diagnose active TB.

Cognitive Impairment in Tuberculous Meningitis.

Cognitive impairment is reported as a common complication in adult tuberculous meningitis (TBM), yet few studies have systematically assessed the frequency and nature of impairment. Moreover, the impact of impairment on functioning and medication adherence has not been described. A cognitive test battery (10 measures assessing 7 cognitive domains) was administered to 34 participants with human immunodeficiency virus (HIV)-associated TBM 6 months after diagnosis. Cognitive performance was compared with that a comparator group of 66 people with HIV without a history of tuberculosis. A secondary comparison was made between participants with TBM and 26 participants with HIV 6 months after diagnosis of tuberculosis outside the central nervous system (CNS). Impact on functioning was evaluated, including through assessment of medication adherence. Of 34 participants with TBM, 16 (47%) had low performance on cognitive testing. Cognition was impaired across all domains. Global cognitive performance was significantly lower in participants with TBM than in people with HIV (mean T score, 41 vs 48, respectively; P < .001). These participants also had lower global cognition scores than those with non-CNS tuberculosis (mean global T score, 41 vs 46; P = .02). Functional outcomes were not significantly correlated with cognitive performance in the subgroup of participants in whom this was assessed (n = 19). Low cognitive performance following HIV-associated TBM is common. This effect is independent of, and additional to, effects of HIV and non-CNS tuberculosis disease. Further studies are needed to understand longer-term outcomes, clarify the association with treatment adherence, a key predictor of outcome in TBM, and develop context-specific tools to identify individuals with cognitive difficulties in order to improve outcomes in TBM.

Human Immunodefiency Virus Infection in Tuberculosis Patients at Kotaraja Health Center of Papua

Human Immunodeficiency Virus (HIV) is a virus that attacks white blood cells and causes the human immune system to decrease. Tuberculosis in HIV patients is an opportunistic infection that will aggravate the disease infection in patients. Examination of HIV (Human Immunodeficiency Virus) in Tuberculosis Patients was carried out at the Kotaraja Health Center. This study was conducted for 1 month starting from May 17, 2019, to June 07, 2019. The purpose of this study was to determine HIV in tuberculosis patients at the Kotaraja Health Center. This type of research is descriptive with a laboratory test approach. The sample used is a serum sample with a diagnosis of HIV. The method used in this examination is the Rapid Test method. The results of HIV testing on tuberculosis patients, sample data obtained from HIV tuberculosis co-infected respondents amounted to 30 HIV respondents who took tuberculosis treatment &gt;6-9 months, negative 6 patients (20%).

Simultaneously Determining Seven Second-Line Anti-TB Drugs by UHPLC- MS: Application for TDM in HIV-TB Patients

Background: To optimize therapy for patients with human immunodeficiency virus-tuberculosis (HIV-TB) coinfection, we developed an ultra-high-performance liquid chromatography/- tandem mass spectrometry (UHPLC-MS) method to monitor seven second-line anti-tuberculosis drugs. Methods: Blood samples (n = 70) were collected from 35 patients with HIV-TB coinfection; the plasma sample was protein-precipitated and diluted with a solution containing heptafluorobutyric acid. The plasma concentrations of rifabutin (RBT), clofazimine (CLO), moxifloxacin (MFX), prothionamide (PTH), levofloxacin (LFX), amikacin (AMK), and para-aminosalicylic acid (PAS) were detected by UHPLC-MS/MS method. Results: In these 70 samples, the mean concentrations of RBT, CLO, MFX, PTH, LFX, and AMK were 173.8 (10.0–550.0), 61.1 (54.4–67.7), 646.6 (25.0–2480.0), 120.5 (50.0–597.0), 1565.9 (100.0–3480.0), and 10753.0 (400.0–76 700.0) μg/L, respectively. Only one sample was detected to have PAS with a concentration less than the lower limit of quantification. Most of the drug concentrations detected in these patients were lower than the targeted concentrations in TB patients. Conclusion: We created a simple UHPLC-MS method for simultaneously quantifying anti-TB drugs. The plasma concentrations in HIV-TB co-infected patients were lower than the targeted concentrations. It is important to monitor anti-TB drugs in the future. This method will facilitate the monitoring of anti-TB drugs in the future.

Clinical features and outcomes of COVID-19 admissions in a population with a high prevalence of HIV and tuberculosis: a multicentre cohort study

BackgroundThere is still a paucity of evidence on the outcomes of coronavirus disease 2019 (COVID-19) among people living with human immunodeficiency virus (PWH) and those co-infected with tuberculosis (TB), particularly in areas where these conditions are common. We describe the clinical features, laboratory findings and outcome of hospitalised PWH and human immunodeficiency virus (HIV)-uninfected COVID-19 patients as well as those co-infected with tuberculosis (TB).MethodsWe conducted a multicentre cohort study across three hospitals in Cape Town, South Africa. All adults requiring hospitalisation with confirmed COVID-19 pneumonia from March to July 2020 were analysed.ResultsPWH comprised 270 (19%) of 1434 admissions. There were 47 patients with active tuberculosis (3.3%), of whom 29 (62%) were PWH. Three-hundred and seventy-three patients (26%) died. The mortality in PWH (n = 71, 26%) and HIV-uninfected patients (n = 296, 25%) was comparable. In patients with TB, PWH had a higher mortality than HIV-uninfected patients (n = 11, 38% vs n = 3, 20%; p = 0.001). In multivariable survival analysis a higher risk of death was associated with older age (Adjusted Hazard Ratio (AHR) 1.03 95%CI 1.02–1.03, p < 0.001), male sex (AHR1.38 (95%CI 1.12–1.72, p = 0.003) and being “overweight or obese” (AHR 1.30 95%CI 1.03–1.61 p = 0.024). HIV (AHR 1.28 95%CI 0.95–1.72, p 0.11) and active TB (AHR 1.50 95%CI 0.84–2.67, p = 0.17) were not independently associated with increased risk of COVID-19 death. Risk factors for inpatient mortality in PWH included CD4 cell count < 200 cells/mm3, higher admission oxygen requirements, absolute white cell counts, neutrophil/lymphocyte ratios, C-reactive protein, and creatinine levels.ConclusionIn a population with high prevalence of HIV and TB, being overweight/obese was associated with increased risk of mortality in COVID-19 hospital admissions, emphasising the need for public health interventions in this patient population.