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Host iron redistribution as a risk factor for incident tuberculosis in HIV infection: an 11-year retrospective cohort study.

ABSTRACT: BACKGROUND:Identifying people at higher risk of developing tuberculosis with human immunodeficiency virus (HIV) infection may improve clinical management of co-infections. Iron influences tuberculosis (TB) pathogenesis, but understanding the exact mechanisms of how and timing of when iron is involved remains challenging since biological samples are rarely available from the disease susceptibility period due to the difficulty in predicting in who and when, if ever, TB will develop. The objective of this research was to determine how host iron status measured at HIV diagnosis and genotypes related to host iron metabolism were associated with incident TB. METHODS:Archived clinical data, plasma and DNA were analyzed from 1139 adult participants in a large HIV-1, HIV-2 and dual seroprevalent cohort based at the Medical Research Council Laboratories in The Gambia. Incident pulmonary and/or extrapulmonary TB diagnoses a minimum of 28 days after HIV diagnosis were independently re-confirmed using available evidence (n=152). Multiple host iron status biomarkers, Haptoglobin and solute carrier family 11, member 1 (SLC11A1) genotypes were modeled to characterize how indicators of host iron metabolism were associated with TB susceptibility. RESULTS:Hemoglobin (incidence rate ratio, IRR=0.88, 95% CI=0.79-0.98), plasma transferrin (IRR=0.53, 0.33-0.84) and ferritin (IRR=1.26, 1.05-1.51) were significantly associated with TB after adjusting for TB susceptibility factors. While genotype associations were not statistically significant, SLC11A1 associations replicated similar directions as reported in HIV-seronegative meta-analyses. CONCLUSIONS:Evidence of host iron redistribution at HIV diagnosis was associated with incident TB, and genetic influences on iron homeostasis may be involved. Low hemoglobin was associated with subsequent diagnosis of TB, but when considered in combination with additional iron status biomarkers, the collective findings point to a mechanism whereby anemia and iron redistribution are likely due to viral and/or bacteria-driven processes and the host immune response to infection. As a result, iron supplementation may not be efficacious or safe under these circumstances. Clinical and nutritional management of HIV and Mycobacterium tuberculosis co-infected individuals, especially in regions where food insecurity and malnutrition co-exist, may be further improved when the iron-related TB risk factors identified here are better understood and managed to favor host rather than pathogen outcomes.

SUBMITTER: McDermid JM

PROVIDER: S-EPMC3568026 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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Host iron redistribution as a risk factor for incident tuberculosis in HIV infection: an 11-year retrospective cohort study.

McDermid Joann M JM Hennig Branwen J BJ van der Sande Marianne M Hill Adrian V S AV Whittle Hilton C HC Jaye Assan A Prentice Andrew M AM

BMC infectious diseases 20130129

<h4>Background</h4>Identifying people at higher risk of developing tuberculosis with human immunodeficiency virus (HIV) infection may improve clinical management of co-infections. Iron influences tuberculosis (TB) pathogenesis, but understanding the exact mechanisms of how and timing of when iron is involved remains challenging since biological samples are rarely available from the disease susceptibility period due to the difficulty in predicting in who and when, if ever, TB will develop. The ob ...[more]

PMID: 23360117

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Project description:BackgroundPredicting the risk of tuberculosis (TB) in people living with HIV (PLHIV) using a single test is currently not possible. We aimed to develop and validate a clinical algorithm, using baseline CD4 cell counts, HIV viral load (pVL), and interferon-gamma release assay (IGRA), to identify PLHIV who are at high risk for incident active TB in low-to-moderate TB burden settings where highly active antiretroviral therapy (HAART) is routinely provided.Materials and methodsA prospective, 5-year, cohort study of adult PLHIV was conducted from 2006 to 2012 in two hospitals in Taiwan. HAART was initiated based on contemporary guidelines (CD4 count < = 350/μL). Cox regression was used to identify the predictors of active TB and to construct the algorithm. The validation cohorts included 1455 HIV-infected individuals from previous published studies. Area under the receiver operating characteristic (ROC) curve was calculated.ResultsSeventeen of 772 participants developed active TB during a median follow-up period of 5.21 years. Baseline CD4 < 350/μL or pVL ≥ 100,000/mL was a predictor of active TB (adjusted HR 4.87, 95% CI 1.49-15.90, P = 0.009). A positive baseline IGRA predicted TB in patients with baseline CD4 ≥ 350/μL and pVL < 100,000/mL (adjusted HR 6.09, 95% CI 1.52-24.40, P = 0.01). Compared with an IGRA-alone strategy, the algorithm improved the sensitivity from 37.5% to 76.5%, the negative predictive value from 98.5% to 99.2%. Compared with an untargeted strategy, the algorithm spared 468 (60.6%) from unnecessary TB preventive treatment. Area under the ROC curve was 0.692 (95% CI: 0.587-0.798) for the study cohort and 0.792 (95% CI: 0.776-0.808) and 0.766 in the 2 validation cohorts.ConclusionsA validated algorithm incorporating the baseline CD4 cell count, HIV viral load, and IGRA status can be used to guide targeted TB preventive treatment in PLHIV in low-to-moderate TB burden settings where HAART is routinely provided to all PLHIV. The implementation of this algorithm will avoid unnecessary exposure of low-risk patients to drug toxicity and simultaneously, reduce the burden of universal treatment on the healthcare system.

Project description:BackgroundPulmonary hypertension incidence based on echocardiographic estimates of pulmonary artery systolic pressure in people living with HIV remains unstudied. We aimed to determine whether people living with HIV have higher incidence and risk of pulmonary hypertension than uninfected individuals.MethodsIn this retrospective cohort study, we evaluated data from participants in the Veterans Aging Cohort Study (VACS) referred for echocardiography with baseline pulmonary artery systolic pressure measures of 35 mm Hg or less. Incident pulmonary hypertension was defined as pulmonary artery systolic pressure higher than 35 mm Hg on subsequent echocardiogram. We used Poisson regression to estimate incidence rates (IRs) of pulmonary hypertension by HIV status. We then estimated hazard ratios (HRs) by HIV status using Cox proportional hazards regression. We further categorised veterans with HIV by CD4 count or HIV viral load to assess the association between pulmonary hypertension risk and HIV severity. Models included age, sex, race or ethnicity, prevalent heart failure, chronic obstructive pulmonary disease, hypertension, smoking status, diabetes, body-mass index, estimated glomerular filtration rate, hepatitis C virus infection, liver cirrhosis, and drug use as covariates.FindingsOf 21 314 VACS participants with at least one measured PASP on or after April 1, 2003, 13 028 VACS participants were included in the analytic sample (4174 [32%] with HIV and 8854 [68%] without HIV). Median age was 58 years and 12 657 (97%) were male. Median follow-up time was 3·1 years (IQR 0·9-6·8) spanning from April 1, 2003, to Sept 30, 2017. Unadjusted IRs per 1000 person-years were higher in veterans with HIV (IR 28·6 [95% CI 26·1-31·3]) than in veterans without HIV (IR 23·4 [21·9-24·9]; p=0·0004). The risk of incident pulmonary hypertension was higher among veterans with HIV than among veterans without HIV (unadjusted HR 1·25 [95% CI 1·12-1·40], p<0·0001). After multivariable adjustment, this association was slightly attenuated but remained significant (HR 1·18 [1·05-1·34], p=0·0062). Veterans with HIV who had a CD4 count lower than 200 cells per μL or of 200-499 cells per μL had a higher risk of pulmonary hypertension than did veterans without HIV (HR 1·94 [1·49-2·54], p<0·0001, for those with <200 cell μL and HR 1·29 [1·08-1·53], p=0·0048, for those with 200-499 cells per μL). Similarly, veterans with HIV who had HIV viral loads of 500 copies per mL or more had a higher risk of pulmonary hypertension than did veterans without HIV (HR 1·88 [1·46-2·42], p<0·0001).InterpretationHIV is associated with pulmonary hypertension incidence, adjusting for risk factors. Low CD4 cell count and high HIV viral load contribute to increased pulmonary hypertension risk among veterans with HIV. Thus, as with other cardiopulmonary diseases, suppression of HIV should be prioritised to lessen the burden of pulmonary hypertension in people living with HIV.FundingNational Heart, Lung, and Blood Institute (National Institutes of Health, USA); National Institute on Alcohol Abuse and Alcoholism (National Institutes of Health, USA).

Project description:ObjectivesTo assess the incidence and predictors of time to Tuberculosis (TB) development among Human Immunodeficiency Virus (HIV) positive patients attending follow-up care in health facilities of Hawassa, Ethiopia.MethodsWe conducted a retrospective cohort study from April 1-30, 2023. A total of 422 participants were selected using a simple random sampling method. Data was collected from the medical records of patients enrolled between January 1, 2018 -December 31, 2022, using the Kobo toolbox. We used Statistical Package for Social Studies (SPSS) version 26.0 for data analysis. To estimate the duration of TB-free survival, we applied the Kaplan-Meier survival function and fitted Cox proportional hazard models to identify the predictors of time to TB development. Adjusted hazard ratios (AHR) with 95% confidence intervals were calculated and statistical significance was declared at a P-value of 0.05.ResultsThe overall incidence rate of TB among HIV-positive patients was 6.26 (95% CI: 4.79-8.17) per 100 person-years (PYs). Patients who did not complete TB Preventive Therapy (TPT) were more likely to have TB than those who did (AHR = 6.2, 95% CI: 2.34-16.34). In comparison to those who began antiretroviral therapy (ART) within a week, those who began after a week of linkage had a lower risk of TB development (AHR = 0.44, 95% CI: 0.21-0.89). Patients who received ART for six to twelve months (AHR = 0.18, 95% CI: 0.05-0.61) and for twelve months or longer (AHR = 0.004, 95% CI: 0.001-0.02) exhibited a decreased risk of TB development in comparison to those who had ART for less than six months.ConclusionThe incidence of TB among HIV-positive patients is still high. To alleviate this burden, special attention should be given to regimen optimization and provision of adherence support for better completion of TPT, sufficient patient preparation, thorough clinical evaluation for major (Opportunistic Infections) OIs prior to starting ART, and ensuring retention on ART.

Project description:A retrospective cohort study was conducted to determine the situation, trend, and factors associated with TB infection, and factors related to the life status among the HIV/AIDS Hill-tribe in Northern Thailand. Hill-tribe people have been migrating to and formed settlements along the Thai border areas for many decades. There are now having 1.6 million people of 6 different groups-Akha, Lahu, Lisu, Hmong, Yao and Keren-each with a specific culture, language and lifestyle. The Hill-tribe becomes a new vulnerable of HIV and TB infections in Thailand.A systematic data-reviewing approach was used to identify the information from the rosters of ARV clinics, OPD cards, and laboratory reports from 16 hospitals in Chiang Rai Province, Thailand. The data were collected from the first reported HIV/AIDS case of the Hill-tribe to the end of 2010. A chi-square test and logistic regression models were used to identify associations at the significance level of alpha = 0.05.A total of 3,130 cases were included in the study. The majority of patients were Akha (46.0 %) followed by Lahu (19.7 %), 54.6 % were males, 44.6 % were 26-35 years old. The major risk factor of HIV infection was sexual intercourse (93.1 %); 23.9 % were still alive at the date of data collection, 30.7 % were diagnosed with pulmonary TB. The Akha Hill-tribe HIV/AIDS individuals had a greater chance of TB infection than did Yao individuals with ORadj = 1.50 (95 % CI = 1.01-1.92). Females had a greater chance of TB infection than males with ORadj = 1.33 (95 % CI = 1.11-1.59); being classified as HIV and AIDS groups had a greater chance of TB infection than those asymptomatic group with ORadj = 11.59 (95 % CI = 7.19-18.71), and ORadj = 1.71 (95 % CI = 1.03-2.87); and not having received the ARV group had a greater chance of TB infection than those who having received the ARV group with ORadj = 2.59 (95 % CI = 2.09-3.22). The patients who had been diagnosed with HIV infection during 1990-1995 and 1996-2000 had less chance of TB infection than those who were diagnosed from 2006-2010, with ORadj = 0.04 (95 % CI = 0.01-0.14) and 0.11 (95 % CI = 0.07-0.17), respectively. Regarding life status; females had a better chance of being still alive at the date of data collection than being males with ORadj = 1.41 (95 % CI = 1.19-1.66). Those who had a defined route of transmission in the category of "mother-to-child" and "IDU" had a better chance of being still alive compared to those who contracted HIV from "sexual intercourse," with ORadj = 2.05 (95 % CI = 1.56-2.18), and ORadj = 8.45 (95 % CI = 1.55-46.13), respectively.Thailand needs to create a TB and HIV/AIDS surveillance system for Hill-tribe populations to determine the situation and trend and to develop an appropriate model for providing care at the earlier stage of HIV/AIDS infection to prevent later TB infection.

Dataset Information

Host iron redistribution as a risk factor for incident tuberculosis in HIV infection: an 11-year retrospective cohort study.

Publications

Host iron redistribution as a risk factor for incident tuberculosis in HIV infection: an 11-year retrospective cohort study.

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