Active Tuberculosis In HIV-infected Patients Research Articles

THE ASSOCIATION BETWEEN GENETIC POLYMORPHISMS OF TOLL-LIKE RECEPTORS AND MANNOSE-BINDING LECTIN AND ACTIVE TUBERCULOSIS IN HIV-INFECTED PATIENTS

Objectives: to analyze the association between genetic polymorphisms of Toll-like receptors (TLR) and mannose-binding lectin (MBL) and active tuberculosis in HIV-infected patients to consider the possibility of using genetic markers as a way to personalize the chemoprophylaxis of tuberculosis in this category of patients. Materials and methods : The study enrolled 171 patients (85 HIV-infected, 86 HIV/TB co-infected patients). Single nucleotide polymorphisms (SNP) in the TLR4 (rs4986790), TLR2 (rs5743708) and MBL2 (rs5030737, rs1800450, rs1800451) were genotyped by real-time PCR and pyrosequencing. Data about epidemiological risk factors were obtained from epidemiological anamnesis. Immune status was assessed by the level of CD4+ T-cells count. Results : Statistically significant association with active tuberculosis was identified for the genotype AG of TLR4, rs4986790 (OR=5.2; 95% CI: 1,8–14,6, p=0,002). Multivariate analysis shows that close contact with TB patientand status of ex-prisoner increased the risk of active tuberculosis 5,2 times (OR=5,2; 95% CI: 1,4–18,5, p=0,012 and OR=5,2; 95% CI: 1,5–17,7, p=0,009, respectively); CD4+ T-cell count more than 200 cells/mm 3 exerted protective effect and reduced the risk of developing TB 5 times (OR=0,2; 95% CI: 0,1–0,5, p=0,001). The genotype AG of TLR4, rs4986790 increased the risk of active tuberculosis 3,7 times (OR=3,7; 95% CI: 1,1–13,1, p=0,046). Conclusion . The G allele of TLR4, rs4986790 can be considered as an independent risk factor for active tuberculosis in HIV-infected individuals. These results need to be confirmed by further investigations on large samples.

Evaluation of a chest radiograph reading and recording system for tuberculosis in a HIV-positive cohort

To assess the impact of introducing a chest radiograph reading and recording system (CRRS) with a short training session, on the accuracy and inter-reader variability of tuberculosis (TB) interpretation of chest radiographs (CXRs) by a group of non-expert readers in a human immunodeficiency virus (HIV)-positive cohort. A set of 139 CXRs was reviewed by a group of eight physicians pre- and post-intervention at two clinics in Shan State, Myanmar, providing HIV/TB diagnosis and treatment services. The results were compared against the consensus of expert radiologists for accuracy. Overall accuracy was similar pre- and post-intervention for most physicians with an average area under the receiver operating characteristic curve difference of 0.02 (95% confidence interval: -0.03, 0.07). The overall agreement among physicians was poor pre- and post-intervention (Fleiss κ=0.35 and κ=0.29 respectively). The assessment of agreement for specific disease patterns associated with active TB in HIV-infected patients showed that for intrinsically subtle findings, the agreement was generally poor but better for the more intrinsically obvious disease patterns: pleural effusion (Cohen's kappa range = 0.37-0.67) and milliary nodular pattern (Cohen's kappa range = 0.25-0.52). This study demonstrated limited impact of the introduction of a CRRS on CXR accuracy and agreement amongst non-expert readers. The role in which CXRs are used for TB diagnosis in a HIV-positive cohort in similar clinical contexts should be reviewed.

Intention of physicians to implement guidelines for screening and treatment of latent tuberculosis infection in HIV-infected patients in The Netherlands: a mixed-method design.

BackgoundAll newly diagnosed HIV-infected patients in the Netherlands should be screened for latent tuberculosis infection (LTBI) and offered preventive therapy if infected without evidence of active tuberculosis. This guideline, endorsed by the national professional body of HIV physicians is in line with international recommendations, and based on the increased risk of progression from LTBI to active tuberculosis in HIV-infected patients. The objective of the study is to assess the intention of HIV physicians to implement this national guideline.MethodsA mixed method design triangulating results from two surveys among all (n = 80) HIV physicians in The Netherlands and qualitative interviews among 11 Dutch HIV physicians performed in 2014.ResultsThe majority of physicians used a risk-stratification approach based on individual a priori risk of tuberculosis to identify HIV-infected patients for LTBI screening, rather than screening all new HIV-infected patients. The intended and actual provision of preventive treatment was low, due to expressed doubts on the accuracy of diagnostic tools for LTBI. Interviewees reported that the guidelines did not match their clinical experience and lacked evidence for the recommendations. Screening for and treatment of LTBI was approached at a patient-level only. None of the interviewees referred to potential public health implications of the guidelines.ConclusionsIntended implementation of the national HIV-TB guidelines in the Netherlands is poor, due to a disconnect between clinical practice and evidence-based recommendations in the guideline. There is an urgent need to reconcile the views of HIV-physicians, public health experts, and guideline committee members, regarding the best strategy to address HIV-TB co-infection in the Netherlands.Electronic supplementary materialThe online version of this article (doi:10.1186/s12889-016-3539-2) contains supplementary material, which is available to authorized users.

Risk of Active Tuberculosis in HIV-Infected Patients in Taiwan with Free Access to HIV Care and a Positive T-Spot.TB Test.

BackgroundInterferon-gamma release assays (IGRAs) have been used to identify individuals at risk for developing active tuberculosis (TB). However, data regarding the risk of TB development in HIV-infected patients testing positive for IGRAs remain sparse in the era of combination antiretroviral therapy.MethodsBetween 2011 and 2013, 608 HIV-infected patients without active TB undergoing T-Spot.TB testing were enrolled in this prospective observational study at a university hospital designated for HIV care in Taiwan with a declining TB incidence from 72 per 100,000 population in 2005 to 53 per 100,000 population in 2012. All of the subjects were followed until September 30, 2014. The national TB registry was accessed to identify any TB cases among those lost to follow-up.ResultsT-Spot.TB tested negative in 534 patients (87.8%), positive in 64 patients (10.5%), and indeterminate in 10 patients (1.6%). In multivariate analysis, positive T-Spot.TB was significantly associated with older age (adjusted odds ratio [AOR], 1.172 per 10-year increase; 95% confidence interval [CI], 1.022-1.344, P=0.023), past history of TB (AOR, 13.412; 95% CI, 6.106-29.460, P<0.001), and higher CD4 counts at enrollment (AOR, per 50-cell/μl increase, 1.062; 95% CI, 1.017-1.109, P=0.007). Of the 64 patients testing positive for T-Spot.TB, none received isoniazid preventive therapy and all but 5 received combination antiretroviral therapy at the end of follow-up with the latest CD4 count and plasma HIV RNA load being 592.8 cells/μL and 1.85 log10 copies/mL, respectively. One patient (1.6%) developed active TB after 167 person-years of follow-up (PYFU), resulting in an incidence rate of 0.599 per 100 PFYU. None of the 534 patients testing negative for T-Spot.TB developed TB after 1380 PYFU, nor did the 24 patients with old TB and positive T-Spot.TB tests develop TB after 62.33 PYFU.ConclusionsThe risk of developing active TB in HIV-infected patients with positive T-Spot.TB receiving combination antiretroviral therapy is low in Taiwan where the national TB program has led to a sustained decrease in TB incidence.

Polyfunctional T-cells and effector memory phenotype are associated with active TB in HIV-infected patients

Polyfunctional T-cells associate with chronic viral infection control while their involvement in tuberculosis (TB) is unclear. We evaluated TB-specific polyfunctional T-cell response and memory status in antiretroviral treatment (ART)-naïve HIV-infected patients from a low TB-endemic country. We prospectively enrolled HIV-infected patients, 12 with active TB (HIV-TB) and 15 with latent tuberculosis infection (LTBI). Peripheral blood cells were stimulated with TB antigens (RD1 proteins/peptides), HIV antigens, cytomegalovirus (CMV) and staphylococcal enterotoxin B (SEB) and analyzed by cytometry. The HIV-TB showed a higher frequency of polyfunctional CD4(+) T-cells in response to RD1 antigens than HIV-LTBI (p = 0.007). Among the CD8(+) T-cells, both groups showed a significantly higher frequency of RD1-specific monofunctional cells than polyfunctional cells (p = 0.03). Analyzing the cytokine profile, IFNγ(+) TNFα(+) CD4(+) T-cells associated with HIV-TB (p ≤ 0.02) whereas IL2(+) TNFα(+) associated with HIV-LTBI (p = 0.009). CD4(+) T-cell response presented an effector-memory status in HIV-TB (p = 0.007) and an effector-memory terminally-differentiated phenotype in HIV-LTBI (p = 0.03). CD8(+) T-cell response presented an effector status in HIV-LTBI (p = 0.02). No significant cytokine profile pattern associated with responses to the other stimuli tested. In HIV-infection, polyfunctional CD4(+) T-cell-response associates with active TB, characterized by a high proportion of IFNγ(+) TNFα(+) and an effector-memory phenotype.

Comparative performance of urinary lipoarabinomannan assays and Xpert MTB/RIF in HIV-infected individuals

Xpert MTB/RIF ('Xpert') and urinary lipoarabinomannan (LAM) assays offer rapid tuberculosis (TB) diagnosis, but have suboptimal sensitivity when used individually in HIV-positive patients. The yield of these tests used in combination for the diagnosis of active TB among HIV-infected TB suspects is unknown. Study of comparative diagnostic accuracy nested into a prospective study of HIV-infected individuals with signs and/or symptoms of TB in Uganda. Xpert testing of archived sputum was conducted for culture-confirmed TB cases and TB suspects in whom a diagnosis of TB was excluded. Additional testing included sputum smear microscopy, sputum culture (solid and liquid media), mycobacterial blood culture, and urinary testing for LAM using a lateral flow test ('LF-LAM') and an enzyme-linked immunosorbance assay ('ELISA-LAM'). Among 103 participants with culture-confirmed TB, sensitivity of Xpert was 76% (95% confidence interval, CI 0.66-0.84), and was superior to that of LF-LAM (49%, 95% CI 0.39-0.59, P < 0.001). Specificity was greater than 97% for both tests among 105 individuals without TB. The combination of smear microscopy and LF-LAM identified 67% (95% CI 0.57-0.76) of culture-confirmed TB cases and approached sensitivity of Xpert testing alone (P = 0.15). The sensitivity of the combination of Xpert and LF-LAM was 85% (88/103 95% CI 0.77-0.92), which was superior to either test alone (P < 0.05) and approached sensitivity of sputum liquid culture testing (94%, 95% CI 0.88-0.98, P = 0.17). Sputum Xpert and urinary LAM assays were complementary for the diagnosis of active TB in HIV-infected patients, and sensitivity of the combination of these tests was superior to that of either test alone.

Incidence of and risk factors for active tuberculosis in human immunodeficiency virus-infected patients in South Korea

In South Korea, a high-income country with an intermediate tuberculosis (TB) burden and low human immunodeficiency virus (HIV) prevalence, studies on incidence and risk factors of TB in HIV-infected persons have rarely been reported. To investigate the incidence of and risk factors for active TB in HIV-infected persons in South Korea. A retrospective analysis was conducted of 1265 HIV-1 infected patients who visited four hospitals in South Korea between 1985 and 2012. We analysed the incidence of TB during the follow-up period. To investigate risk factors associated with active TB, we conducted a 1:2 matched case-control study of HIV-infected patients with newly active TB and controls without active TB who had similar CD4(+) T-cell counts and dates of first visit. Over a total of 4457 person-years (py), 185 (14.6%) subjects were diagnosed with active TB; the incidence was 4.2 cases/100 py. In multivariate analysis, low body mass index (P = 0.033) and current smoking (P = 0.003) were independent risk factors for TB in HIV-infected patients. Further strategies on prevention and treatment of active TB among HIV-infected patients should be implemented in South Korea. Encouraging smoking cessation and supporting good nutrition may be ways to reduce the incidence of active TB in HIV-infected patients.

Interferon-gamma release assays for the diagnosis of active tuberculosis in HIV-infected patients: a systematic review and meta-analysis.

BackgroundInterferon-gamma release assays (IGRAs) have provided a new method for the diagnosis of Mycobacterium tuberculosis infection. However, the role of IGRAs for the diagnosis of active tuberculosis (TB), especially in HIV-infected patients remains unclear.MethodsWe searched PubMed, EMBASE and Cochrane databases to identify studies published in January 2001–July 2011 that evaluated the evidence of using QuantiFERON-TB Gold in-tube (QFT-GIT) and T-SPOT.TB (T-SPOT) on blood for the diagnosis of active TB in HIV-infected patients.ResultsThe search identified 16 eligible studies that included 2801 HIV-infected individuals (637 culture confirmed TB cases). The pooled sensitivity for the diagnosis of active TB was 76.7% (95%CI, 71.6–80.5%) and 77.4% (95%CI, 71.4–82.6%) for QFT-GIT and T-SPOT, respectively, while the specificity was 76.1% (95%CI, 74.0–78.0%) and 63.1% (95%CI, 57.6–68.3%) after excluding the indeterminate results. Studies conducted in low/middle income countries showed slightly lower sensitivity and specificity when compared to that in high-income countries. The proportion of indeterminate results was as high as 10% (95%CI, 8.8–11.3%) and 13.2% (95%CI, 10.6–16.0%) for QFT-GIT and T-SPOT, respectively.ConclusionIGRAs in their current formulations have limited accuracy in diagnosing active TB in HIV-infected patients, and should not be used alone to rule out or rule in active TB cases in HIV-infected patients. Further modification is needed to improve their accuracy.

T-SPOT.TB in the Diagnosis of Active Tuberculosis Among HIV-Infected Patients with Advanced Immunodeficiency

We evaluated the performance of T-SPOT.TB (a commercial interferon gamma release assay) and its accuracy for the diagnosis of active tuberculosis (TB) among HIV-infected subjects with advanced immunodeficiency. In a clinical prospective study, we assessed the performance of T-SPOT.TB for the diagnosis of active TB in HIV-infected patients with CD4 cell counts below 350 cells/mm(3) who were naive to antiretroviral and anti-TB therapies. Results were available from 147 patients, of whom 38 (25.9%) had active TB. The majority (85%) of the participants were male, with a median age of 40 years and a median CD4 cell count of 77 cells/mm(3). T-SPOT.TB yielded 15 (10.2%) indeterminate results. The indeterminate results were not associated with CD4 cell counts. However, younger patients were more likely to have an indeterminate result (OR = 0.91 per unit increase in age, p = 0.007). After excluding the indeterminate results, the sensitivity of T-SPOT.TB for the diagnosis of active TB was 37.1% and the specificity was 88.7%. The sensitivity of the T-SPOT.TB was independent of the CD4 cell count. However, its specificity was higher when used for patients with CD4 cell counts <100 cells/mm(3) when compared to patients with CD4 cell counts ≥100 cells/mm(3) (97.9% vs. 79.6%, p = 0.008). T-SPOT.TB could not be used as a routine tool to screen for active TB among HIV-infected patients with advanced immunodeficiency because of its poor performance and low sensitivity. However, it may be used as an adjunctive tool to diagnose active TB in this population due to its high specificity.

Development of opportunistic infections after diagnosis of active tuberculosis in HIV-infected patients.

Despite advances in highly active antiretroviral therapy (HAART), its use during tuberculosis (TB) treatment is fraught with challenges, often leading to delayed therapy. This report describes the course of HIV infection and outcomes of 26 consecutive TB/HIV coinfected patients who received TB treatment in Rhode Island. HIV infection was diagnosed in 26 (4%) of 598 TB cases in during a 10-year period. Of these patients, TB was the first indication of HIV infection in 15 patients (58%). Of the 21 patients who were not on antiretrovirals at the time of TB diagnosis, 17 (81%) met criteria for immediate initiation of HAART. The median CD4 cell counts and HIV-1 plasma viral load were 80 cells per microliter (range, 2-800 cells per microliter) and 255,631 copies per milliliter (range, 50,000 to > 500,000 copies per milliliter), respectively, for the patients whose baseline measurements were available. CD4 lymphocyte count was less than 200 cells per microliter in 13 (76%) of the 17 patients whose measurements were available. Three (30%) of the 10 patients whose CD4 cell count was less than 100 cells per microliter developed subsequent AIDS-defining illness prior to the initiation of HAART and a fourth patient, within 30 days of starting HAART. None of the patients who had CD4 cell counts 100 cells per microliter or greater developed subsequent AIDS-defining illness during TB treatment. The median time to starting HAART after starting TB treatment was 12 weeks (range, 3-36 weeks). From our limited experience based on this case series, we recommend early initiation of HAART in coinfected patients with CD4 cell counts less than 100 cells per microliter.

Tuberculosis and HIV Infection: Epidemiology, Immunology, and Treatment

Tuberculosis and HIV have combined to present a major threat to global public health. Each disease has a negative effect on the other, and mortality in patients with both tuberculosis and HIV is higher than that caused by either condition alone. In regions such as sub-Saharan Africa, as many as a third or more of all patients with tuberculosis have concomitant HIV infection. In urban centers in developed nations, HIV co-infection may also be quite common. Treatment of latent tuberculosis infection in persons with HIV is successful in preventing many cases of active disease, and newer ultra-short course regimens, such as those consisting of 2 months of rifampin and pyrazinamide, should aid in this effort. Diagnosis and treatment of active tuberculosis in HIV-infected patients may be difficult. Although treatment of active tuberculosis is generally successful in patients with HIV, drug interactions between anti-tuberculosis medications and antiretrovirals often complicate the matter, and expert guidance should be sought for proper management.