Human Immunodeficiency Virus Tuberculosis Co-infection Research Articles

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.

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.

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 < 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.

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.

Peculiarities of persons who inject drugs among patients with HIV–tuberculosis coinfection registered in 4thDistrict TB Unit Bucharest during 2009–2018

AbstractIntroduction: Human immunodeficiency virus (HIV)–tuberculosis (TB) coinfection is a worldwide problem and a subject of concern, being associated with high mortality and risk of complications. Intravenous drug use is a way of getting infected with HIV that continues to rise, especially in the big cities. We aimed to study the peculiarities of persons with HIV–TB who inject drugs.Methods: We performed a retrospective, observational study, among patients treated for TB in the 4thDistrict TB unit, Bucharest, during a 10-year period. A unique registry of patients with TB was used, and data of all patients with HIV–TB were noted ( demographics, medical, treatment outcome). A comparison between drug users (people who inject drugs [PWID]) and nondrug users (non-PWID) was assessed.Results: We identified 122 patients with HIV–TB: 60 PWID, 58 non-PWID, and 4 former users. The mean age was 36.4 ± 9.8 years, 75% were males, and 73% were using antiretroviral treatment (ART). After comparing PWID with non-PWID patients, the following differences were noted: age (33.0 ± 6.0 years in PWID vs 40.5 ± 11.3 in non-PWID, P < 0.0001), gender (87% vs 66% males, P = 0.0034), presence of chronic hepatitis (97% vs 21%, P < 0.0001), CD4 number (156.1 ± 204.5 cells/mm3vs 260.8 ± 248.9 cells/mm3, P = 0.0409), ART (65% vs 84%, P = 0.0075), and evaluation at the end of TB treatment (P = 0.0373).Conclusions: PWID represent a vulnerable population of those with HIV–TB coinfection, whose outcome in TB treatment is significantly poorer and who are at risk of abandonment, death, and comorbidities. They should be included in dedicated programmes that are aimed at increasing adherence to treatment and care, additionally assessing the dependence problem.

Simultaneous determination of first-line anti-tuberculosis drugs and one metabolite of isoniazid by liquid chromatography/tandem mass spectrometry in patients with human immunodeficiency virus-tuberculosis coinfection

The incidence rate of tuberculosis (TB) in patients with human immunodeficiency virus (HIV) infection is 26 times higher than that in other patients. Patients with both infections require long-term combination therapy, which increases therapy complexity and might lead to serious adverse reactions and drug-drug interactions. To optimize therapy for patients with HIV and TB coinfection, we developed an ultra-high-performance liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS) method to simultaneously quantify four anti-tuberculosis drugs and one isoniazid (INH) metabolite. Blood samples (n = 32) from 16 patients with HIV and TB coinfection were collected. Plasma protein precipitation with acetonitrile was followed by a hydrazine reaction between INH and cinnamaldehyde (CA) to produce phenylhydrazone (CA-INH) and dilution with heptafluorobutyric acid. The separation was performed on an Acquity UHPLC HSS T3 1.8 μm column (2.1 × 100 mm, Waters) with a mobile phase consisting of 10 mmol/L ammonium formate (pH = 4) in water (solvent A) and 0.1 % formic acid in methanol (solvent B) in a gradient elution. The compounds were detected using a positive multiple reaction monitoring model. INH, acetyl-INH (AC-INH), rifampicin (RIF), ethambutol (EMB), and pyrazinamide (PZA) showed good linear relationships in their quantitative ranges, with lower limits of quantification of 48, 192, 200, 96, and 480 ng/mL, respectively. The inter- and intraday precision was within 15 %, and the accuracy was between 85 % and 115 %. The mean plasma concentrations of INH, AC-INH, RIF, EMB, and PZA in patients were 1990.23 (24–16 600), 863.06 (96–2880), 3507.05 (229–9800), 808.10 (149–2130), and 18 838.33 (240–34 800) ng/mL, respectively. The plasma concentrations detected in the 16 patients were lower than the targeted concentrations in HIV-negative TB patients. In summary, we developed a simple UHPLC-MS/MS method for simultaneous quantification of first-line TB drugs, and successfully applied it for therapeutic drug monitoring in patients with HIV and TB coinfection. This method will facilitate monitoring of TB drugs in the future.

Defective Antigen Presentation Leads to Upregulation of PD1 and IL-10 in HIV-TB Co-Infection.

Human immunodeficiency virus-tuberculosis (HIV-TB) co-infection poses a challenge to the immunologists in developing new diagnostic and therapeutic tools. Mechanisms behind the breakdown of the immune defense of the co-infected individual are poorly known. Numerous studies in HIV alone have revealed the role of PD1, TAP, and IL-10, but not in co-infection. The interaction of the 2 distinct bugs, which is resulting in domination over the host immune system, is still a lacuna. Hence, we aimed to portray functions of IL-10, TAP, and PD1 molecules in HIV-TB co-infection. Co-culture cells challenged with γ-irradiated M.Tb under various conditions resulted in high interleukin (IL)-10 secretion and high percentage of PD1 expression on CD8 T cells, which might be due to defective antigen presentation of TAP on dendritic cells and macrophages. Herein our observations provide an insight into the escape mechanisms by M.Tb in HIV-infected individuals from the host immune responses leading to TB co-infection.

Prevalence and determinants of HIV in tuberculosis patients in Wuxi City, Jiangsu province, China: a cross-sectional study

At least one-third of the 34 million people living with human immunodeficiency virus (HIV) worldwide are infected with latent tuberculosis (TB). The aim of this study was to determine the rate of HIV infection in TB patients and its determinants in Wuxi City, China. TB patients attending health institutions (12 selected sites) for TB diagnosis and treatment were enrolled in this study. TB diagnosis, treatment and HIV testing were done according to the national guidelines. Blood samples were collected for anonymous HIV testing. Among the TB patients, the HIV prevalence was 13.66% (1493/10,926). Multivariate analysis showed that gender, age, education, marital status, per capita monthly income, patient residence, family size, distance from a health institution, knowledge of HIV-TB co-infection, and knowledge of HIV may be risk factors for HIV-TB co-infection (all: odds ratio > 1, p < 0.05). The prevalence of TB in those with HIV was higher among the study participants. Improving public awareness of HIV-TB co-infection, regularly screening and improving follow-up can reduce the occurrence of HIV-TB co-infection.

Programmatic and ethical challenges in the implementation of treatment-as-prevention in the context of HIV and drug-resistant tuberculosis co-infection in sub-Saharan Africa

There is limited literature on programmatic challenges in the implementation of a treatment-as-prevention (TasP) strategy among human immunodeficiency virus (HIV) and drug-resistant tuberculosis (DR-TB) co-infected individuals in sub-Saharan Africa (SSA). This paper highlights specific programmatic challenges surrounding the implementation of this strategy among HIV and DR-TB co-infected populations in SSA. In SSA, limitations in administrative, human and financial resources and poor health infrastructure, as well as increased duration and complexity of providing long-term treatment for HIV individuals co-infected with DR-TB, pose substantial challenges to the implementation of a TasP strategy and warrant further investigation. A comprehensive approach must be devised to implement TasP strategy, with special attention paid to the sizable HIV and DR-TB co-infected populations. We suggest that evidence-informed and human rights–based guidelines for participant protection and strategies for programme delivery must be developed and tailored to maximise the benefits to those most at risk of developing HIV and DR-TB co-infection. Assessing regional circumstances is crucial, and TasP programmes in the region should be complemented by combined prevention strategies to achieve the intended goals.

Association of TAP 1 and 2 gene polymorphisms with human immunodeficiency virus–tuberculosis co-infection

Major histocompatibility complex (MHC) class I binding peptides are carried from cytosol to the lumen of the endoplasmic reticulum (ER) by transporter associated with antigen processing (TAP), an integral ER membrane protein composed of two subunits, TAP1 and TAP2. Polymorphism in TAP genes may influence these proteins further affecting the antigen peptide presentation, indirectly resulting in the viral escape mechanism from cell-mediated immunity in human immunodeficiency virus (HIV). Our aim was to study the influence of these polymorphism in study groups with HIV–tuberculosis (TB) (n = 110), TB (n = 105), and HIV (n = 130) compared with healthy controls (n = 183), using the tetraprimer amplification refractory mutation system (ARMS)–polymerase chain reaction method. Our results demonstrated that the GG genotype at TAP1 position 333 and GA genotype at TAP1 position 637 were positively associated with HIV-TB co-infection and these genotypes may act as a risk factor for developing TB co-infection in HIV-positive individuals.

Immune reconstitution inflammatory syndrome presenting as chylothorax in a patient with HIV and Mycobacterium tuberculosis coinfection: a case report

BackgroundPatients with human immunodeficiency virus (HIV) infection are at risk for Mycobacterium tuberculosis (TB) coinfection. The advent of antiretroviral therapy restores immunity in HIV-infected patients, but predisposes patients to immune reconstitution inflammatory syndrome (IRIS).Case PresentationA 25-year-old HIV-infected male presented with fever, productive cough, and body weight loss for 2 months. His CD4 cell count was 11 cells/μl and HIV-1 viral load was 315,939 copies/ml. Antituberculosis therapy was initiated after the diagnosis of pulmonary TB. One week after antituberculosis therapy, antiretroviral therapy was started. However, multiple mediastinal lymphadenopathies and chylothorax developed. Adequate drainage of the chylothorax, suspension of antiretroviral therapy, and continued antituberculosis therapy resulted in successful treatment and good outcome.ConclusionsChylothorax is a rare manifestation of TB-associated IRIS in HIV-infected patients. Careful monitoring for development of IRIS during treatment of HIV-TB coinfection is essential to minimize the associated morbidity and mortality.