Tuberculosis In HIV-infected Patients Research Articles

Causes of Late Diagnosis of Tuberculosis in HIV Patients

The objective: to determine causes of frequent detection of disseminated tuberculosis in HIV-infected patients taking into account the behavioral characteristics of patients, to propose additional measures to enhance tuberculosis detection.Subjects and Methods. 108 questionnaires filled out by TB/HIV co-infected patients staying in specialized hospitals in 3 regions of the Russian Federation were studied. We filled out the first 18 questionnaires ourselves while talking to patients, to assess whether the questions were clear to patients. The questionnaire included 28 questions with prompted answers; in addition, patients could give their own answers. Using the questionnaire, we found out whether the patients were seeking medical help in a timely manner, units to which they referred, awareness of tuberculosis before developing it, and exposure to tuberculous infection.Results. The majority of interviewed patients with previously diagnosed HIV infection did not undergo medical examination at the Center for AIDS Prevention and Control (CAIDSPC). When complaints associated with tuberculosis appeared, 57/108 (52.8%) respondents referred to the clinic at their place of residence. In 56/108 (51.8%) patients, 2 or more months passed from the moment of referral for medical help to diagnosis and initiation of tuberculosis treatment. 7/108 (6.5%) respondents reported history of tuberculosis, and 4/108 (3.7%) respondents reported exposure to a tuberculosis patient. After developing tuberculosis, 20/108 (18.5%) respondents were exposed to other HIV-infected patients. After detection of HIV infection, 93 (86.1%) patients indicated that they had not been made aware of tuberculosis.

Trends in and Risk Factors for Drug Resistance in Mycobacterium tuberculosis in HIV-Infected Patients.

Trends in and risk factors for drug resistance in Mycobacterium tuberculosis (M. tuberculosis) in human immunodeficiency virus (HIV)-infected patients with active tuberculosis were analyzed. The clinical data of M. tuberculosis and HIV-coinfected patients treated at the Shanghai Public Health Clinical Center between 2010 and 2022 were collected. The diagnosis of tuberculosis was confirmed by solid or liquid culture. The phenotypic drug susceptibility test was carried out via the proportional method, and the resistance to first-line and second-line drugs was analyzed. Logistic regression analysis was performed to identify associated risk factors for drug resistance in M. tuberculosis. Of the 304 patients with a M. tuberculosis-positive culture and first-line drug susceptibility test results, 114 (37.5%) were resistant to at least one first-line anti-tuberculosis drug. Of the 93 patients with first-line and second-line drug susceptibility test results, 40 (43%) were resistant to at least one anti-tuberculosis drug, and 20 (21.5%), 27 (29.0%), 19 (20.4%), 16 (17.2%), and 14 (15.1%) were resistant to rifampicin, streptomycin, ofloxacin, levofloxacin, and moxifloxacin, respectively; 17 patients (18.3%) had multidrug-resistant tuberculosis (MDR-TB). Between 2010 and 2021, the rate of resistance to streptomycin and rifampicin ranged from 14.3% to 40.0% and from 8.0% to 26.3%, respectively, showing an increasing trend year by year. From 2016 to 2021, the rate of resistance to quinolones fluctuated between 7.7% and 27.8%, exhibiting an overall upward trend. Logistic regression analysis showed that being aged <60 years old was a risk factor for streptomycin resistance, mono-drug resistance, and any-drug resistance (RR 4.139, p = 0.023; RR 7.734, p = 0.047; RR 3.733, p = 0.009). Retreatment tuberculosis was a risk factor for resistance to rifampicin, ofloxacin, of levofloxacin (RR 2.984, p = 0.047; RR 4.517, p = 0.038; RR 6.277, p = 0.014). The drug resistance rates of M. tuberculosis to rifampicin and to quinolones in HIV/AIDS patients were high and have been increasing year by year. Age and a history of previous anti-tuberculosis treatment were the main factors associated with the development of drug resistance in HIV/AIDS patients with tuberculosis.

Efficacy of Preventive Chemotherapy of Tuberculosis in HIV Infected Patients in Novosibirsk Oblast

The objective: to study the efficacy of tuberculosis preventive chemotherapy in HIV infected patients based on the data of AIDS Prevention and Control Center, which is a part of City Infectious Clinical Hospital no. 1, Novosibirsk.Subjects and Methods. 236 HIV infected patients aged 33-48 years old were enrolled in the study, they all were registered in AIDS Prevention and Control Center, City Infectious Clinical Hospital no. 1, Novosibirsk. All patients were at the stage of secondary diseases (4A, 4B, 4C), and had a pronounced degree of immunodeficiency (CD4+ from 200 to 349 cells/µl), and the ongoing ART was virologically successful. The efficacy of tuberculosis preventive chemotherapy (CTX) was analyzed in 147 patients versus 89 patients who received no tuberculosis CTX due to various reasons. For tuberculosis preventive chemotherapy, a combination drug was used, which contained isoniazid and pyrazinamide, for 3 months with daily intake. The groups of those receiving and not receiving CTX were comparable in terms of the gender, age and degree of immunodeficiency.Results. In the group receiving CTX within a year after completion of CTX, tuberculosis was diagnosed in 7/147 (4.8%) patients including: focal pulmonary tuberculosis - in 71.4% (5/7), and infiltrative pulmonary tuberculosis - in 28.6% (2/7 patients). In the group receiving no CTX, during the year, 17/89 (19.1%) tuberculosis cases were detected: focal pulmonary tuberculosis – in 29.4% (5/17), infiltrative pulmonary tuberculosis - in 47.1% (8/17), and disseminated pulmonary tuberculosis - in 23.5% (4/17). Disseminated pulmonary tuberculosis was registered only in the group who received no CTX. The relative risk (RR = 0.442 (&lt;1)) when comparing the number of cases in the groups indicates lower likelihood to develop tuberculosis in the patients taking CTX. The odds ratio (OR = 0.212; CI 0.084-0.534) indicates that the chances of developing tuberculosis are higher in the group receiving no CTX.Conclusion. The use of a combination of isoniazid and pyrazinamide for tuberculosis preventive chemotherapy in HIV infected patients significantly reduces the risk of developing tuberculosis. Patients with severe immunodeficiency who have contraindications to tuberculosis preventive chemotherapy should be followed up jointly with a phthisiologist, the follow-up should include computed tomography for early detection of tuberculosis signs in the lungs.

Identification of additional ways to reduce the incidence of tuberculosis in HIV-infected patients. Retrospective Continuum Study.

Background: HIV infection was more often registered in the general population than in vulnerable groups according to official statistics from the Russian Federation in 2021.&#x0D; Aims: to determine the characteristic patient cohorts coinfected with tuberculosis (TB) and HIV in dynamic epidemiological environments, and propose additional organizational approaches for reducing TB incidence in patients with HIV.&#x0D; Materials and methods: we have investigated complete medical data for patients coinfected with TB and HIV in three Russian regions. Additionally, we analyzed the cohort of patients with TB, combined with HIV infection via sexual transmission. Furthermore, confidential interviews with patients coinfected with TB and HIV were undertaken. In particular, reasons for refusing clinical examination at a Russian Federal AIDS Center (RFAIDSC) were clarified.&#x0D; Results: among patients coinfected with TB and HIV, parenteral transmission remains the primary HIV infection route. At the same time, patients who become infected through sexual contact are also primarily socially disadvantaged, leading to the refusal of clinical examination and a consequent late detection of TB. On the other hand, patients report that due to unemployment, they do not have the financial means to travel to the regional RFAIDSC.&#x0D; More often, widespread, rapidly progressive MDR TB infections occurred among patients coinfected with TB and HIV, than for patients with TB but without HIV. Considering that every fourth TB patient in Russia has been diagnosed with HIV, and, at the same time, there are specific features regarding the development and course of TB, the generally accepted criteria for assessing the quality of TB without HIV care often become biased for coinfected patients. This can lead to unreasonably negative assessments of the antituberculosis system and its work.&#x0D; Conclusions: in view of the above, it is important to modify regulatory documents regarding informing patients about the importance of seeking timely medical help, solve the issue of travel for unemployed patients to medical examinations and in emergency cases. Additionally, it is important to introduce adjustments for the criteria in assessing the quality of patient TB care, thereby accounting for the pathogenesis of TB in patients with HIV coinfection.

Performance of Xpert MTB/RIF for Diagnosis of Tuberculosis in HIV-Infected People in China: A Retrospective, Single-Center Study.

BackgroundThere are few studies of GeneXpert MTB/RIF (hereafter referred to as Xpert) detection technology in HIV-infected people in China. Therefore, this study aimed to evaluate the value of Xpert in HIV/TB co-infected patients and to provide reference and guidance for the diagnosis of TB in HIV-infected populations.Material/MethodsThis study reviewed medical records of human immunodeficiency virus (HIV) patients hospitalized at the Infection Center of Beijing Ditan Hospital affiliated to Capital Medical University from January 2018 to May 2020, and patients diagnosed with pulmonary and extrapulmonary tuberculosis were screened as study subjects. Sensitivity and specificity of Xpert were analyzed using ROC curves.ResultsOf the 413 HIV patients, 177 patients met the entry criteria, of which the diagnosis was active pulmonary tuberculosis (PTB): 145 and extrapulmonary tuberculosis (EPTB): 32. The sensitivity of Xpert for PTB and EPTB was 82.0% and 100%, higher than that of acid-fast bacilli (AFB) (61.0% and 58.3%), and slightly lower than that of T-SPOT.TB (91.0% and 100%); the specificity was 83.7% and 93.5%, higher than that of AFB (72.6%, 87.1%) and T-SPOT.TB (16.6%, 21.2%). The sensitivity of Xpert was 100% in bronchoalveolar lavage fluid (BALF) and 80.0% in sputum; in patients with CD4+ <200 cells/mm3, the sensitivity of Xpert was 90.0% and specificity was 84.8%, higher than that of AFB (60.0%, 75.5%) and T-SPOT.TB (90.0%, 21.5%).ConclusionsXpert has a high accuracy in HIV/TB co-infected patients, and Xpert still shows a high sensitivity and specificity even in HIV patients with CD4+ <200 cells/mm3. Xpert is recommended for the diagnosis of tuberculosis in HIV-infected patients.

Manifestations of epidemic process of tuberculosis among HIV-infected patients and dependence of infection frequency on immunodeficiency level and HIV viral load

Objective. To assess the manifestations of the epidemic process of tuberculosis (TB) in HIV-infected persons and the frequency of infection depending on the level of immunodeficiency and viral load.&#x0D; Materials and methods. The epidemiological manifestations of TB incidence among HIV-infected and HIV-negative population of the Perm Region for 20142019 were studied. The frequency of TB in HIV-infected patients was determined depending on the level of immunodeficiency (96 patients) and viral load (61 patients).&#x0D; Results. On average, the incidence of TB among HIV-infected persons was by 36 times higher than that of noninfected persons. Among those infected and noninfected with HIV, TB was registered significantly more often among adults, and mainly men. The incidence of TB among HIV-infected persons is higher among urban population, while HIV-negative among rural residents. The incidence of TB in HIV-infected persons increases with an increase in the immunodeficiency and viral load.&#x0D; Conclusions. Persons with HIV infection are at risk for TB. The incidence of TB in HIV-infected persons increases with an increase in immunodeficiency and viral load.

Valuation of Cavities in the Lungs Among HIV/TB Patients

Early diagnosis of respiratory tuberculosis among HIV-infected patients improves the prognosis of recovery and reduces mortality. The emergence of cavities is one of the patterns of the progression of pulmonary tuberculosis. The article analyzes the results of examination of HIV-infected tuberculosis patients with cavities. We estimate the data of anamnesis, the disease clinic and immune status. The retrospective study included patients of the Leningrad region with HIV/TB with early respiratory tuberculosis from 2014 to 2016 (n = 852). We identified a clear relationship between chemoprophylaxis and antiretroviral therapy on developing tuberculosis non-cavity, but no direct relationship was found with widespread or disseminated TB. We also obtained a significantly relationship between the bacterial excretion and the detection of destruction in the lung tissue on the background a pronounced decrease in the immune status (CD4 100 cells/μl or less). There are statistically significant decreases in the frequency of cavities of respiratory tuberculosis and the proportion of etiologically verified cases is in case in the suppression of immunity (CD4 100 cells/μl or less). However, the relationship between early mortality from tuberculosis (during the first year) and pulmonary tuberculosis with cavities was not obtained.

Epidemiological analysis of factors influencing the course of multidrug-resistant tuberculosis in HIV-infected patients with concomitant viral hepatitis

The epidemiological significance of combined forms of especially dangerous infections has not been studied enough, unlike mono-infections. Currently, there is a tendency towards an increase in the incidence of multidrug-resistant tuberculosis. The formation of severe forms of the disease is caused by other widespread infections, such as chronic viral hepatitis and HIV. Polymorbid conditions distort the clinical manifestations of tuberculosis, reduce the effectiveness of anti-tuberculosis therapy and worsen the prognosis of the disease. Risk factors among patients in this category need analysis to carefully monitor patients and ensure infection control. Objective is to analyze the factors affecting the course of multidrug-resistant tuberculosis in HIV-infected patients with concomitant viral hepatitis. Materials and methods. Cases of the combined pathology of multiresistant tuberculosis, HIV infection and viral hepatitis with a dominant diagnosis of tuberculosis are analyzed. Results and discussion. The influence of the immunological status on the course of combined pathology was revealed. Since all the patients under study had clinical stage 4 of HIV infection, tuberculosis developed as an opportunistic infection. Severe immunosuppression (CD4 200 cells/ml) contributed to the progression of the generalized tuberculosis process. Long-term immunodeficiency was an unfavorable factor; in the overwhelming majority of cases, antiretroviral therapy was prescribed only after tuberculosis was detected. The dependence of the clinical form of tuberculosis on the level of CD4-lymphocytes was noted: isolated lesion of the chest organs prevailed in patients with a level of CD4-lymphocytes more than 200 cells/ml, generalization of TB process — with CD4 less than 200 cells/ml. Patients with miliary tuberculosis had a higher mortality rate compared to patients with other clinical forms, regardless of antiretroviral therapy. It was revealed that socially disoriented young people with viral hepatitis C prevailed in the structure of patients, the prevalence of which was due to the influence of aggravating factors, such as alcohol and drug abuse, and stay in prisons. Against the background of combined treatment, there was no significant effect of viral hepatitis on the course of polymorbid conditions and the effectiveness of the therapy.

Increased risk of IRIS-associated tuberculosis in HIV-infected patients receiving Integrase Inhibitors

BackgroundTuberculosis is associated with a risk of immune reconstitution inflammatory syndrome (IRIS) after ART initiation. MethodsData from all patients with newly diagnosed tuberculosis disease and uncontrolled HIV infection from 1997 to 2017 in a French center were retrospectively collected. We evaluated the incidence of tuberculosis-IRIS in patients initiating ART with or without integrase inhibitors (INSTI) ResultsFifty-five patients were included: 21 receiving an INSTI regimen and 34 a non-INSTI regimen. Except with regard to ART regimen, the two groups were comparable (median CD4 of 85/mm3). The overall percentage of IRIS was 34% (19/55), with 52% IRIS in INSTI regimen and 23% in non-INSTI regimen respectively (P=0.04). In a multivariate logistic model, we observed an increased risk of IRIS in the INSTI regimen compared to the non-INSTI, with an OR at 3.33 [95% CI, 1.01–11.1] (P=0.05) ConclusionsART containing integrase inhibitors could be associated with increased incidence of TB-associated IRIS.

Diagnostic value of interferon-γ release assay in HIV-infected individuals complicated with active tuberculosis: a systematic review and meta-analysis.

Although the interferon-γ release assay (IGRA) has become a common diagnostic method for tuberculosis, its value in the diagnosis of tuberculosis in human immunodeficiency virus (HIV) seropositive patients remains controversial. Therefore, this systematically reviews the data for exploring the diagnostic value of IGRA in HIV-infected individuals complicated with active tuberculosis, aiming to provide a clinical basis for future clinical diagnosis of the disease. Relevant studies on IGRA for diagnosing tuberculosis in HIV-infected patients were comprehensively collected from Excerpta Medica Database (EMBASE), Medline, Cochrane Library, Chinese Sci-tech Periodical Full-text Database, Chinese Periodical Full-text Database, China National Knowledge Infrastructure (CNKI) and China Wanfang Data up to July 2020. Subsequently, Stata 15.0, an integrated statistical software, was used to analyse the sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratio (PLR) and negative likelihood ratio (NLR) to create receiver operator characteristic (ROC) curves. A total of 18 high-quality articles were selected, including 20 studies, 11 of which were related to QuantiFERON-TB Gold In-Tube (QFT-GIT) and nine to T-SPOT.TB. The meta-analysis indicated that the pooled sensitivity = 0.75 (95% CI 0.63-0.85), the pooled specificity = 0.82 (95% CI 0.66-0.92), PLR = 4.25 (95% CI 1.97-9.18), NLR = 0.30 (95% CI 0.18-0.50), DOR = 14.21 (95% CI 4.38-46.09) and the area under summary ROC curve was 0.85 (95% CI 0.81-0.88). IGRA has a good diagnostic value and therefore can aid in the preliminary screening of active tuberculosis in HIV-infected individuals. Its diagnostic effectiveness can be improved by modifying and optimizing the assay design.

CD4 response of treatment-naive HIV-TB patients with lower respiratory tract infections in a tertiary care hospital in North India

Background: Most patients develop lower respiratory tract infections of infectious etiology during the course of human immunodeficiency virus (HIV) infection. High burden of tuberculosis (TB) among HIV-infected patients leads to lowering of immunity, thus increasing the incidence of other opportunistic infections. The present study was conducted to discuss the impact of lower respiratory tract infections(LRTI's) including TB in HIV-infected patients. Materials and Methods: A prospective case–control study was done on 180 treatment-naive HIV-seropositive patients and 100 HIV-seronegative controls having LRTIs for a period of 1 year. Expectorated and induced sputum samples were collected and screened for Mycobacterium tuberculosis by smear microscopy. Five milliliter of venous blood was collected from each patient for determination of cluster of differentiation 4+ (CD4+) T-cell lymphocyte counts. Results: Acid-fast bacilli were observed in 40.55% (73/180) of HIV-infected patients compared to 17% (17/100) in seronegative patients (P < 0.001). About 69.86% (51/73) of HIV-TB co-infected patients had CD4 + T-cell lymphocyte count < 200 cells/μl (P < 0.05). CD4 + T-cell lymphocyte counts of HIV-TB co-infected patients were comparable to patients having LRTI's other than TB (P > 0.05). Conclusion: LRTIs lead to a significant lowering of CD4 + T-cell lymphocyte counts among HIV-positive patients. Hence, routine screening along with laboratory confirmation for all lower respiratory tract infections in addition to TB is essential to manage coinfections in HIV patients.

Outcomes and complications of hospitalised patients with HIV-TB co-infection.

Tuberculosis is one of the most common causes of hospitalisation in patients with HIV. Despite this, hospital outcomes of patients with this co-infection have rarely been described since antiretroviral therapy became widely available. Prospective cohort study of HIV-infected adult patients hospitalised with TB in six referral hospitals in Medellin, Colombia, from August 2014 to July 2015. Among 128 HIV-infected patients hospitalised with tuberculosis, the mean age was 38.4years; 79.7% were men. HIV was diagnosed on admission in 28.9% of patients. The median CD4+T-cell count was 125 (±158 SD) cells/µL. Only 47.3% of patients with a known diagnosis of HIV upon admission were on antiretroviral therapy, and only 11.1% had a tuberculin skin test in the previous year. Drug toxicity due to tuberculosis medications occurred in 11.7% of patients. Mean length of stay was 23.2days, and 10.7% of patients were readmitted. Mortality was 5.5%. Hospital mortality attributable to tuberculosis in patients with HIV is low in reference hospitals in Colombia. Cases of tuberculosis in HIV-infected patients occur mainly in patients with advanced HIV, or not on antiretroviral therapy, despite a known diagnosis of HIV. Only one of every 10 patients in this cohort had active screening for latent tuberculosis, possibly reflecting missed treatment opportunities.

The use of computer techniques to optimize the diagnosis of tuberculosis in HIV-infected patients at the secondary diseases stage

ВACKGROUND: The course of tuberculosis in HIV-infected patients has no significant clinical and diagnostic differences from damage to organs and systems of other etiology. The growth of new cases of HIV/TB co-infection necessitates a revision of diagnostic approaches, their improvement in order to increase the efficiency of examination and management of HIV-infected patients, depending on the stage and indicators of the immune status.&#x0D; AIM: Of the study was to determine by the method of complex statistical processing the main clinical and laboratory-instrumental criteria for improving the diagnosis of tuberculosis in HIV-infected patients at the stage of secondary diseases.&#x0D; MATERIALS AND METHODS: The study design was retrospective. The object of the research was the case histories of 113 patients with HIV infection at the stage of secondary diseases (classification by V.I. Pokrovsky), of parametric and nonparametric statistics, computer analysis of images with the gradient program proposed by Dr. Sci. A.N. Gerasimov, to assess the possibility of using micro- and macro-preparations of tissues and organs of patients with HIV infection.&#x0D; RESULTS: Using the method of correlation adaptometry, it was found that there are no significant differences in the clinical course of HIV-infected patients with tuberculosis of various localization, and with lesions of the respiratory organs of other etiology. The use of multivariate probability models made it possible to identify significant diagnostic risk factors for lethal outcome ― 66.7% of patients with further lethal outcome complained of chest pain during breathing (p=0.004), and ESR was significantly accelerated in patients with a lethal outcome in the hospital ― 771.99 (p=0.019).&#x0D; CONCLUSION: The multicomplex instrumental and laboratory examination makes it possible to diagnose tuberculosis of various localization at the initial stage of development. The use of computer techniques optimizes and unifies the diagnostic search in patients with HIV infection and determines the timely treatment tactics.

Fluorescent methods in morphological diagnostics of respiratory tuberculosis in HIV-infected patients

Background. Among the spectrum of respiratory diseases in HIV-infected patients, the leading place is taken by tuberculosis (TB). First of all, difficulties in the morphological diagnostics of TB are associated with the smooth over of its typical histological signs under condition of severe immunodeficiency. To objectify the histological conclusion about the presence of tuberculosis lesion in a morphology a number of specific histochemical and fluorescent methods have been developed, which are based on the direct or indirect detection of M. tuberculosis (MBT) in the affected tissues. Objective – to determine the advisability and effectiveness of using of fluorescent methods in the morphological diagnostics of respiratory tuberculosis in HIV-infected patients. Methods. The morphological study included 37 cases. Two methods were used: the traditional fluorescent method (FM) and immunohistochemical study with a polyclonal antibody to M. Tuberculosis with a fluorescent label (FITC). In the study group, the histological conclusions were compared with the final clinical diagnosis and the results of microbiological investigations. The sensitivity, specificity and effectiveness have been established for each of the methods. Results. At hospitalization only in one third of cases, based on the results of clinical and radiological data and laboratory tests, various forms of respiratory TB were suspected. In 26 cases (70,3 %), with traditional staining of tissue samples with hematoxylin and eosin, a histological diagnosis of tuberculosis infection was established. When performing FM, the largest number of positive results was obtained (16 cases, 84,2 %), whereas with FITC, the MBT was detected only in 11 cases (57,9 %). The specificity of the FITC method was 90,5 %, and FM – 84,6 %. The overall efficiency of the parallel application of 2 fluorescent methods was 69,1 %. The coincidence of the results of both methods was noted in 22 cases of 31 (70,9 %). In total, of the using of morphological fluorescent methods, mycobacterium infection in HIV-infected patients was diagnosed in 29 cases (78,4 %), and in 4 cases (10,8 %) mycobacterium infection was established as a background pathology. Conclusion. At the time of hospitalization, in more than half of patients with HIV infection (59,5 %), the results of clinical laboratory and radiological data do not allow determining the true nature of the pathological process. The traditional study of histological samples stained with hematoxylin and eosin made it possible to diagnose mycobacterial infection in 70,3 % of cases. The use of fluorescent methods increased the efficiency of morphological diagnosis of mycobacterial infection by 10,8 %. The fluorescence method showed a high sensitivity (88,0 %), while indicator of specificity was higher with the immunofluorescence method (90,5 %). The overall efficiency of using fluorescent methods for the histological detection of M. tuberculosis was 69,1 %, which indicates the advisability of using these methods in cases of diagnostics mycobacterial infection.

Factors Influencing Utilisation of Diagnostic Counselling and Testing for HIV among Tuberculosis Patients at Monze Mission Hospital, Zambia

Factors Influencing Utilisation of Diagnostic Counselling and Testing for HIV among Tuberculosis Patients at Monze Mission Hospital, Zambia

The single recombinant M. tuberculosis protein DPPD provides enhanced performance of skin testing among HIV-infected tuberculosis patients

Diagnostic testing for M. tuberculosis infection has advanced with QuantiFERON and GeneXpert, but simple cost-effective alternatives for widespread TB screening has remained elusive and purified protein derivative (PPD)-based tuberculin skin testing (TST) remains the most widely used method. PPD-based tests have reduced performance, however, in BCG vaccinees and in individuals with immune deficiencies. We compared the performance of skin testing with the recombinant DPPD protein against that of a standard PPD-based skin test. Our data indicates similar performance of DPPD and PPD (r2 = 0.7689) among HIV-negative, active TB patients, all of whom presented greater than 10 mm induration following administration. In contrast to results demonstrating that PPD induced indurations greater than 5 mm (i.e., the recommended threshold for positive results in this population) in only half (19 of 38) of the HIV positive TB patients, 89.5% (34 of 38) of these participants developed indurations greater than 5 mm when challenged with DPPD. Importantly, none of the patients that were positive following PPD administration were negative following DPPD administration, indicating markedly improved sensitivity of DPPD among HIV-infected individuals. Our data indicate that DPPD has superior performance in skin testing than the current TST standard.

Tuberculosis Chemotherapy Outcome in the Littoral Region of Cameroon: A Meta-analysis of Treatment Success Rate between 2014 and 2016.

Background Tuberculosis (TB) is a public health concern, especially in resource-constrained countries like Cameroon. TB drug resistance is a major obstacle to control and prevent. Design Data from 2014 to 2016 on the outcome of anti-TB treatment in the Littoral Region were reviewed manually and analysed using the meta-analysis concept. The treatment success rates (TSR) were the primary outcome used for this study. The heterogeneity statistics (I2) was computed to orientate the choice of the best statistical model (binary fixed effect or random) to compute pooled value of TSR. Results Using an intention-to-treat analysis, the pooled proportions of HIV-uninfected TB patients successfully cured from TB were low and slightly decreased by 1% between 2014 and 2016. Regarding HIV-infected TB patients, pooled values of TSR were lower than those of their HIV-negative counterparts with values ranging from 71% (95% CI: 63%-83%; I2 = 71.16%) in 2014 to 68% (95% CI: 58%-79%; I2 = 70.97%) in 2016. In addition, no heterogeneity was found in three years (I2 = 0.0%; P value = 1). These cure rates were strongly and negatively correlated with the rates of patients lost to follow-up regardless of the year. In HIV-infected patients, the pooled values of ITT analysis-based treatment success rates were 73% (χ2 = 13.92, P value = 0.0002), 71% (χ2 = 7.26, P value = 0.007), and 68% (χ2 = 8.02, P value = 0.004), respectively. The coverage rates with cotrimoxazole (CTX) gradually increased over year ranging from 78.90% in 2014 to 94.17% in 2016, similar to the coverage rate for ARV therapy that was 60.06% in 2014 against 90% in 2016. A positive and statistically significant correlation was found between the success of the anti-TB therapy in HIV-infected patients and coverage rates with CTX and ARV. Conclusion An improvement in the reduction of percentage of lost to follow-up and coverage with CTX and ARV therapy could greatly increase chances to efficiently control TB in Cameroon.

Role of CD4/CD8 ratio on the incidence of tuberculosis in HIV-infected patients on antiretroviral therapy followed up for more than a decade.

The role of CD4/CD8 ratio on the incidence of tuberculosis (TB) in patients on antiretroviral therapy (ART) is unknown. Thus, we sought to determine whether the CD4/CD8 ratio was associated with development of TB in a cohort of HIV infected individuals on ART followed up for more than a decade in the setting of sub-Saharan Africa (SSA). The cohort comprised adult patients who started ART between 2001 and 2007 and followed for up to 15 years. Clinical data were collected in retrospective manner. Patients with an AIDS defining illness or a CD4 count <200 cell/μL were started with a combination of ART. The participants have clinic visits every 6 months and/or as needed. Poisson regression models were used to identify factors associated with development of incident TB. Kaplan-Meier curves were used to estimate the probability of incident TB while on ART. A total of 347 patients with a median duration of follow-up on ART of 11.5 (IQR: 10.0-12.5) years were included. Incident TB developed in 47 patients during the 3259 person-years of follow-up, the majority (76.6%) occurred within five year of ART initiation. On univariate analysis, poor ART adherence (RR:2.57, 95% CI: 1.28-5.17), time-updated CD4 cell count of lower than 200 (RR: 4.86, 95%CI 2.33-10.15), or CD4 cell count between 200 and 500 (RR: 4.68, 95% CI: 2.17-10.09), time-updated CD8 cell count lower than 500 (RR: 2.83 95% CI 1.31-6.10), or CD8 cell count over 1000 (RR: 2.23, 95% CI: 1.12-4.45), time-updated CD4/CD8 ratio of less than 0.30 (RR: 6.00, 95% CI: 2.96-12.14), lack of normalization of CD4 T-cell count (RR: 6.13, 95% CI: 2.20-17.07), and virological failure (RR: 2.35 (95% CI: 1.17-4.71) were all associated with increased risk of incident TB. In multivariate analysis, however, time-updated CD4/CD8 ratio of less than 0.30 (adjusted RR: 4.08, 95% CI: 1.31-12.68) was the only factor associated with increased risk of developing incident TB (p = 0.015). Similar results were obtained in a sensitivity analysis by including only those virally suppressed patients (n = 233, 69% of all patients). In this group, CD4/CD8 ratio of less than 0.30 was associated with development of incident TB (adjusted RR: 4.02, 95% CI: 1.14-14.19, p = 0.031). Overall, the incidence rate of TB in patients with an updated CD4/CD8 ratio of less than 0.30 was more than 5-fold higher when compared with those with a ratio more than 0.45. Low CD4/CD8 ratio is independently associated with an increased risk of incident TB despite viral suppression. CD4/CD8 ratio may serve as a biomarker for identifying patients at risk of TB in patients on ART in the setting of SSA.

Discovery of Potential Plasma Biomarkers for Tuberculosis in HIV-Infected Patients by Data-Independent Acquisition-Based Quantitative Proteomics.

PurposeTuberculosis (TB) is the leading cause of mortality in individuals infected with human immunodeficiency virus (HIV), yet the methods for detecting Mycobacterium tuberculosis at an early stage remain insensitive or ineffective. This study aimed to discover plasma biomarkers for distinguishing HIV-TB coinfected individuals from HIV individuals without TB (HIV-nonTB).Patients and MethodsA total of 200 Chinese HIV-positive patients were recruited, 100 each for HIV-nonTB group and HIV-TB group. Plasma proteomic profiles were analyzed for 50 patients each in both groups, using data-independent acquisition (DIA)-mass spectrometry-based proteomics. Differently expressed proteins were revealed with ridge regression analysis. Enzyme-linked immunosorbent assay (ELISA) analyses were performed for further validation in other 100 patients.ResultsDIA-mass spectrometry revealed 13 upregulated and 33 downregulated proteins in the HIV-TB group. AMACR (α-methylacyl-CoA racemase), LDHB (L-lactate dehydrogenase B chain), and RAP1B (Ras-related protein Rap-1b) were selected for building a diagnostic model, for which the receiver operation characteristic curve had under areas of 0.99 and 0.89 testing with proteomics data (sensitivity = 92%, specificity = 100%) and ELISA data (sensitivity = 76%, specificity = 92%), respectively.ConclusionThe combination of AMACR, LDHB, and RAP1B proteins may serve as a potential marker of TB in HIV-infected patients.

What Are the Barriers for Uptake of Antiretroviral Therapy in HIV-Infected Tuberculosis Patients? A Mixed-Methods Study from Ayeyawady Region, Myanmar.

Antiretroviral therapy (ART) coverage among HIV-infected tuberculosis (HIV-TB) patients has been suboptimal in Myanmar and the reasons are unknown. We aimed to assess the ART uptake among HIV-TB patients in public health facilities of Ayeyawady Region from July 2017–June 2018 and explore the barriers for non-initiation of ART. We conducted an explanatory mixed-methods study with a quantitative component (cohort analysis of secondary programme data) followed by a descriptive qualitative component (thematic analysis of in-depth interviews of 22 providers and five patients). Among 12,447 TB patients, 11,057 (89%) were HIV-tested and 627 (5.7%) were HIV-positive. Of 627 HIV-TB patients, 446 (71%) received ART during TB treatment (86 started on ART prior to TB treatment and rest started after TB treatment). Among the 181 patients not started on ART, 60 (33%) died and 41 (23%) were lost-to-follow-up. Patient-related barriers included geographic and economic constraints, poor awareness, denial of HIV status, and fear of adverse drug effects. The health system barriers included limited human resource, provision of ART on ‘fixed’ days only, weaknesses in counselling, referral and feedback mechanism, and clinicians’ reluctance to start ART early due to concerns about immune reconstitution inflammatory syndrome. We urge the national TB and HIV programs to take immediate actions to improve the ART uptake.