Higher Levels of Alcohol Use Are Associated With Latent Tuberculosis Infection in Adults Living With Human Immunodeficiency Virus.
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ABSTRACT:
SUBMITTER: Puryear SB
PROVIDER: S-EPMC7935375 | biostudies-literature | 2021 Mar
REPOSITORIES: biostudies-literature
Publications
Higher Levels of Alcohol Use Are Associated With Latent Tuberculosis Infection in Adults Living With Human Immunodeficiency Virus.
Puryear Sarah B SB Fatch Robin R Beesiga Brian B Kekibiina Allen A Lodi Sara S Marson Kara K Emenyonu Nneka I NI Muyindike Winnie R WR Kwarisiima Dalsone D Hahn Judith A JA Chamie Gabriel G
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20210301 5
We assessed associations between hazardous alcohol use and latent tuberculosis infection (LTBI) among adults living with human immunodeficiency virus (HIV) in Uganda. We compared tuberculin skin test positivity across medium, high, and very-high alcohol use levels, classified by AUDIT-C scores. In multivariable analysis, very high use was associated with LTBI (adjusted odds ratio 1.61, 95% confidence interval: 1.03-2.50). ...[more]
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Project description:BackgroundIncreased risk of progression from latent tuberculosis infection (LTBI) to tuberculosis (TB) disease among people living with human immunodeficiency virus (HIV; PLWH) prioritizes them for LTBI testing and treatment. Studies comparing the performance of interferon gamma release assays (IGRAs) and the tuberculin skin test (TST) among PLWH are lacking.MethodsWe used Bayesian latent class analysis to estimate the prevalence of LTBI and diagnostic characteristics of the TST, QuantiFERON Gold In-Tube (QFT), and T.SPOT-TB (TSPOT) among a prospective, multicenter cohort of US-born PLWH ≥5 years old with valid results for all 3 LTBI tests using standard US cutoffs (≥5 mm TST, ≥0.35 IU/mL QFT, ≥8 spots TSPOT). We also explored the performance of varying LTBI test cutoffs.ResultsAmong 1510 PLWH (median CD4+ count 532 cells/mm3), estimated LTBI prevalence was 4.7%. TSPOT was significantly more specific (99.7%) and had a significantly higher positive predictive value (90.0%, PPV) than QFT (96.5% specificity, 50.7% PPV) and TST (96.8% specificity, 45.4% PPV). QFT was significantly more sensitive (72.2%) than TST (54.2%) and TSPOT (51.9%); negative predictive value of all tests was high (TST 97.7%, QFT 98.6%, TSPOT 97.6%). Even at the highest cutoffs evaluated (15 mm TST, ≥1.00 IU/mL QFT, ≥8 spots TSPOT), TST and QFT specificity was significantly lower than TSPOT.ConclusionsLTBI prevalence among this cohort of US-born PLWH was low compared to non-US born persons. TSPOT's higher PPV may make it preferable for testing US-born PLWH at low risk for TB exposure and with high CD4+ counts.
| S-EPMC8678585 | biostudies-literature
Project description:BackgroundAlcohol abuse has been associated with HIV/AIDS progression, but the effects of HIV infection and treatment on alcohol exposure have not been explored to date. This pilot study examines the relationship of untreated HIV infection to blood alcohol concentrations (BAC) relative to BAC after initiation of antiretroviral therapy (ART).MethodsFifteen volunteers with untreated HIV/AIDS participated in 2 sets of alcohol or alcohol placebo administration studies before and after initiation of ART. Oral alcohol (1 g/kg) or alcohol placebo was administered, participants were followed for pharmacokinetics, subjective responses, and cognitive effects over 8 hours. After initial alcohol studies, the ART regimen selected by participant clinicians was instituted. Observed ART dosing took place for at least 2 weeks. Participants then returned for a second set of alcohol/placebo administration studies while on ART.ResultsParticipants had significantly higher BAC (P < 0.001) before ART than after ART administration. Alcohol area under the curve was significantly higher in untreated HIV disease (P = 0.011) with significantly higher C(max) (P = 0.015) and C(min) (P = 0.05). The elimination rate was not different between pre-ART and post-ART conditions. Despite declines in BAC after ART initiation, no differences in subjective responses were observed with alcohol administration.ConclusionsUntreated HIV infection is associated with risk for higher BAC than that observed after ART. These findings indicate that patients with untreated HIV disease who ingest alcohol are at greater risk for alcohol associated adverse events and toxicities and underscores the need for simultaneous treatment of alcohol use disorders and HIV in patients with co-occurring conditions.
| S-EPMC3723399 | biostudies-literature
Project description:Even with treatment of HIV with antiretroviral therapy (ART), the risk of tuberculosis (TB) reactivation remains higher in HIV-infected than HIV-uninfected persons. In this issue of the JCI, Ganatra et al. explored TB reactivation in the context of ART using TB and simian immunodeficiency virus-coinfected (TB/SIV-coinfected) nonhuman primates. The authors found that treating rhesus macaques with ART restored CD4+ T cells in whole blood, spleen, and bronchoalveolar lavage (BAL) fluid, but not in the lung interstitium. TB risk was not decreased in the coinfected macaques treated with ART for 14-63 days, suggesting that ART does not decrease the short-term risk of reactivation. Reactivation occurred as CD4+ T cells were increasing, which is consistent with observations made in humans. This study provides a potential model for systematic evaluation of TB/SIV coinfection and different treatment regimens and strategies to prevent TB reactivation.
| S-EPMC7524504 | biostudies-literature
Project description:Homeless persons have disproportionate rates of latent tuberculosis infection (LTBI). LTBI treatment can prevent and reduce active tuberculosis spread. We examined associations between mental health, social support, and perceptions of general health in 50 LTBI-positive, homeless adults enrolled in LTBI treatment. Depression and anxiety prevalence were 40% and 48%, respectively. Depression was negatively associated with general health, positive social interaction, and tangible, emotional/informational, and total social support, and positively associated with severe substance use (ps < 0.05). Anxiety was negatively associated with emotional/informational, tangible and total social support, and positively associated with severe substance use (ps < 0.05). Mental health services may help improve LTBI interventions.
| S-EPMC7972994 | biostudies-literature
Project description:ObjectiveWe aimed to investigate the relationship of metal exposure and latent tuberculosis infection (LTBI) among US adults and adolescents.MethodsParticipants from the National Health and Nutrition Examination Surveys (NHANES 2011 ~ 2012) were included. Multiple logistic regression models were used to explore the associations between metal exposure and LTBI. A total of 5,248 adults and 1,860 adolescents were included in the present analysis.ResultsFor adults, we only found a positive association between total mercury and LTBI (OR: 1.411; 95% CI: 1.164 ~ 1.710) when used as a continuous variable. Compared with Q1, Q4 increased the prevalence of LTBI (2.303; 1.455 ~ 3.644) when used as a quartile. The OR of total mercury and LTBI was higher among females (1.517; 1.009 ~ 2.279), individuals aged 45 ~ 64 (1.457; 1.060 ~ 2.002), and non-Hispanic White individuals (1.773; 1.316 ~ 2.388). A relationship was observed among only participants with obesity (1.553; 1.040 ~ 2.319) or underweight (1.380; 1.076 ~ 1.771), with college or above (1.645; 1.184 ~ 2.286), with PIR > 3.0 (1.701; 1.217 ~ 2.376), reported smoking (1.535; 1.235 ~ 1.907) and drinking (1.464; 1.232 ~ 1.739). For adolescents, blood manganese was positively associated with LTBI. The OR and 95% CIs for each one-unit increase in the log-transformed level of blood manganese with LTBI were 9.954 (1.389 ~ 71.344).ConclusionSignificant associations were observed in girls, aged ≥12 years and in the non-Hispanic white population. In conclusion, total mercury is associated with an increased prevalence of LTBI among adults and positive association between blood manganese and LTBI was observed among adolescents. Further studies should be conducted to verify the results and explore potential biological mechanisms.
| S-EPMC10655142 | biostudies-literature
Project description:BackgroundLack of a gold standard for latent TB infection has precluded direct measurement of test characteristics of the tuberculin skin test and interferon-γ release assays (QuantiFERON Gold In-Tube and T-SPOT.TB).ObjectiveWe estimated test sensitivity/specificity and latent TB infection prevalence in a prospective, US-based cohort of 10 740 participants at high risk for latent infection.MethodsBayesian latent class analysis was used to estimate test sensitivity/specificity and latent TB infection prevalence among subgroups based on age, foreign birth outside the USA and HIV infection.ResultsLatent TB infection prevalence varied from 4.0% among foreign-born, HIV-seronegative persons aged <5 years to 34.0% among foreign-born, HIV-seronegative persons aged ≥5 years. Test sensitivity ranged from 45.8% for the T-SPOT.TB among foreign-born, HIV-seropositive persons aged ≥5 years to 80.7% for the tuberculin skin test among foreign-born, HIV-seronegative persons aged ≥5 years. The skin test was less specific than either interferon-γ release assay, particularly among foreign-born populations (eg, the skin test had 70.0% specificity among foreign-born, HIV-seronegative persons aged ≥5 years vs 98.5% and 99.3% specificity for the QuantiFERON and T-SPOT.TB, respectively). The tuberculin skin test's positive predictive value ranged from 10.0% among foreign-born children aged <5 years to 69.2% among foreign-born, HIV-seropositive persons aged ≥5 years; the positive predictive values of the QuantiFERON (41.4%) and T-SPOT.TB (77.5%) were also low among US-born, HIV-seropositive persons aged ≥5 years.ConclusionsThese data reinforce guidelines preferring interferon-γ release assays for foreign-born populations and recommending against screening populations at low risk for latent TB infection.Trial registration numberNCT01622140.
| S-EPMC6494673 | biostudies-literature
Project description:Purpose of reviewThe present review describes recent advances in the treatment of drug-susceptible tuberculosis (DS-TB) among people living with human immunodeficiency virus (PLWH).Recent findingsHigher than standard rifampicin doses (>10 mg/kg/day) are well tolerated and have improved sterilizing activity. Standard pyrazinamide doses may result in low drug exposures; modeling reveals that higher doses (>25 mg/kg/day) may be required to reach target levels, although safety is unknown. Four-month fluoroquinolone-containing regimens are not recommended in the 2017 World Health Organization DS-TB treatment guidelines. These guidelines also recommend fixed-dose combination (FDC) therapy over single drug formulations based on patient preference, though FDC is not associated with improved outcomes. Treatment for 6 months is recommended, with an emphasis on expanded antiretroviral therapy (ART) coverage and monitoring for relapse among those not started on ART within 8 weeks of tuberculosis treatment. Directly observed therapy (DOT) is recommended over self-administered therapy, as is daily therapy over intermittent therapy - both are associated with better tuberculosis outcomes.SummaryCurrent WHO tuberculosis treatment guidelines recommend 6 months of daily tuberculosis treatment for PLWH who have DS-TB, and timely ART initiation. Higher rifampin and pyrazinamide doses may enhance treatment effectiveness, but safety data are needed. DOT and FDC therapy are recommended.
| S-EPMC6389504 | biostudies-literature
Project description:This follow-up cross-sectional study aimed to analyze the prevalence rate and risk factors related to latent tuberculosis infection (LTBI) and active tuberculosis (TB) in children aged < 15 years in contact with adults with smear-positive pulmonary TB (PTB) in a Brazilian municipality. Data were collected from interviews, clinical evaluations, chest X-rays, tuberculin skin tests, and interferon gamma release assays. The median time elapsed between diagnosis of the index case (IC) and inclusion in the study was 2.5 years (interquartile range [IQR] = 1.5-4.4) and 7.4 years (IQR = 3.8-9.7) when we reassessed the development (or not) of active TB. The median age at the time of exposure to the IC was 6.6 years (IQR = 3.3-9.4) and 14.1 years (IQR = 8.9-17.7) at the last follow-up. Of the 99 children and adolescents in contact with smear-positive PTB, 21.2% (95% CI = 14.0-29.9) were diagnosed with LTBI, and none developed active TB. There was no statistically significant difference between the LTBI and non-LTBI groups regarding demographic, socioeconomic, and epidemiological characteristics. Unlike national and international scenarios, we found a lower frequency of LTBI and no active TB among our studied patients. For better understanding of these findings, further studies might add, among other factors, host and Mycobacterium tuberculosis genetic features.
| S-EPMC6838572 | biostudies-literature
Project description:BackgroundWe previously reported increased unstimulated blood levels of interferon-gamma in persons with latent tuberculosis infection (LTBI) in the United States, suggesting enhanced immune activation in LTBI. To investigate this further in a TB-endemic setting, we assessed interferon-gamma levels in persons with and without LTBI in Peru.MethodsWe analyzed data from patients with and without a recent type 1 (spontaneous) acute myocardial infarction (AMI) who were enrolled from two public hospital networks in Lima, Peru, and underwent LTBI testing using the QuantiFERON® TB Gold In-tube (QFT) assay. Participants with a positive QFT test were defined as having LTBI, whereas participants with a negative QFT test were defined as non-LTBI. Unstimulated interferon-gamma was quantified via enzyme-linked immunosorbent assay in the QFT nil-tube, which does not contain antigens. We compared unstimulated interferon-gamma levels between LTBI and non-LTBI groups using the Wilcoxon rank sum test. We used proportional odds modeling for multivariable analysis.ResultsData from 214 participants were included in this analysis. Of those, 120 (56%) had LTBI. There were no significant differences in age, sex and comorbidities between LTBI and non-LTBI participants, except for recent AMI that was more frequent in LTBI. LTBI participants had higher unstimulated interferon-gamma levels compared to non-LTBI participants (median, interquartile range; 14 pg/mL, 6.5-52.8 vs. 6.5 pg/mL, 4.5-15; P<0.01). LTBI remained associated with higher unstimulated interferon-gamma levels after controlling for age, sex, recent AMI, history of hypertension, diabetes mellitus, dyslipidemia, end stage renal disease, malignancy, obesity, and tobacco use (adjusted odds ratio, 2.93; 95% confidence interval, 1.8-4.9). In a sensitivity analysis that excluded participants with AMI, the association between unstimulated interferon-gamma and LTBI remained present (adjusted odds ratio; 3.93; 95% confidence interval, 1.9-8.2).ConclusionsLTBI was associated with higher unstimulated interferon-gamma levels. These data suggest ongoing immune activation in LTBI.
| S-EPMC6136705 | biostudies-literature
Project description:BackgroundMycobacterium tuberculosis (Mtb) and human immunodeficiency virus (HIV) coinfection increases mortality, accelerates progression to acquired immune deficiency syndrome, and exacerbates tuberculosis disease. However, the impact of pre-existing Mtb infection on subsequent HIV infection has not been fully explored. We hypothesized that Mtb infection creates an immunological environment that influences the course of HIV infection, and we investigated whether pre-existing Mtb infection impacts the susceptibility of CD4+ T cells to HIV-1 infection.MethodsPlasma and blood CD4+ T cells isolated from HIV-negative individuals across the Mtb infection spectrum and non-Mtb-infected control individuals were analyzed for inflammation markers and T-cell phenotypes. CD4+ T cells were infected with HIV-1 in vitro and were monitored for viral replication.ResultsWe observed differences in proinflammatory cytokines and the relative proportion of memory T-cell subsets depending on Mtb infection status. CD4+ T cells derived from individuals with latent Mtb infection supported more efficient HIV-1 transcription, release, and replication. Enhanced HIV-1 replication correlated with higher percentages of CD4+ TEM and TTD cells.ConclusionsPre-existing Mtb infection creates an immunological environment that reflects Mtb infection status and influences the susceptibility of CD4+ T cells to HIV-1 replication. These findings provide cellular and molecular insights into how pre-existing Mtb infection influences HIV-1 pathogenesis.
| S-EPMC7529013 | biostudies-literature