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The objective: to analyze and compare frequency and variety of adverse events (AEs) and their impact on outcomes of tuberculosis therapy when treating patients with multiple drug resistant tuberculosis (MDR TB) and different HIV statuses.Subjects and Methods: retrospective observational case-control study of patients registered for treatment with the 4th regimen of chemotherapy for tuberculosis in the city of Vladimir and Vladimir Region in 2014-2016.Results. The proportion of patients who reported any AE during the MDR TB treatment was similar among HIV positive and HIV negative patients and made 85.5%. In patients with concurrent HIV infection and MDR TB, hematopoietic AEs such as anemia, thrombocytopenia were more frequent, while neutropenia was significantly more frequent when comparing groups by the cumulative event probability method. Elevated eosinophil level during treatment was more typical of MDR TB patients. Treatment outcomes in the group of patients with HIV and MDR TB were statistically significantly worse due to the higher frequency of fatal outcomes. At the same time, there was no correlation of AE with unfavorable treatment outcomes. The early initiation of combination therapy with thorough monitoring of hematologic parameters in patients with HIV and MDR TB was safe and effective.

The objective: to study the frequency and nature of community-acquired pneumonia (CAP) in HIV patients.Subjects and methods: The continuous longitudinal retrospective study of all cases of respiratory diseases among HIV patients (n = 185), who received in-patient treatment in the therapy department.Results. CAP was diagnosed in 38.4% (n = 71) of patients and it was the most frequent respiratory disease among HIV patients. The median CD4 count in CAP made 197.5 cells/μL, 9.1% of patients received antiretroviral therapy before hospital admission. 74.7% of CAP patients (n = 53) had lesions disseminated to several lobes. Laboratory parameters revealed in severe CAP (leukocytosis > 12 × 109/L, leukopenia 0.05). Bacteremia in CAP was detected in 20.8% of patients and it was associated with the failure of standard empiric antibiotic therapy (p

The review analyses 61 publications on the use of delamanid, a new drug for the treatment of drug resistant tuberculosis. It presents information about pharmacokinetic parameters, efficacy and safety, as well as the place of delamanid in the combination therapy of multiple drug resistant tuberculosis. It tells about specific parameters of delamanid use in children and HIV patients.

The review presents information on epidemiology, clinical, laboratory and radiological manifestations of infectious and malignant respiratory diseases in HIV-infected patients.The data on the most common infections (communityacquired pneumonia, tuberculosis, Pneumocystis jiroveci pneumonia) and malignant diseases (Kaposhi’s sarcoma, lymphomas) as well as less frequent diseases (CMV-infection, MAC-infection, fungal pneumonias) are presented.The article contains facts about the incidence of pulmonary diseases according to the severity of HIV-associated immunodeficiency. This review also presents current information on the diagnostic criteria, treatment regimens and secondary prophylaxis for HIV-associated respiratory infections and malignancies. The specialties of ART initiation in definite cases of opportunistic infections and ART assignment during the diagnostic period are highlighted.The growing number of HIV-infected patients and the wide spectrum of possible pulmonary diseases argue the need for optimal clinical approach to HIV-infected patients with respiratory lesions for various physicians (general practitioners, pulmonologists and phthisiatricians).

The review presents literature data on therapeutic and diagnostic management of pulmonary diseases in HIV-infected patients. The article provides different practical approaches in the diagnosis of HIV-associated lung lesions and the spectrum of probable diseases, depending on the degree of immunodeficiency and the severity of clinical manifestations. The reference clinical signs of the most common opportunistic diseases with possible lung involvement are presented.The literature review highlights the feasibility of accurate etiological and invasive diagnosis of lung lesions in different clinical settings, as well as the need to designate various options of empirical antimicrobial therapy. The features of antimicrobial therapy and, in particular, the use of fluoroquinolones during the differential diagnosis of pulmonary lesions in HIV infection are discussed. The difficulties of verifying of HIV-associated lung diseases indicate the need of unified therapeutic and diagnostic approaches for use by various physicians (general practitioners, pulmonologists andphthisiologists).

The objective of the study: to assess the risk to develop active tuberculosis in HIV infected patients with history of substance abuse taking into account their CD4 count.Subjects and methods. A retrospective case-control study was conducted with enrollment of 171 patients: HIV Group included 85 persons, while TB/HIV Group – 86 persons. For screening for chronic alcohol/narcotic intoxication, the CAGE questionnaire was used, and tobacco dependence was detected according to the criteria of World Health Organization. CD4 counts were obtained by the retrospective analysis of medical records. The impact of the studied risk factors on the development of tuberculosis was estimated by calculating the odds ratio with the calculation of the 95% confidence interval.Results. Statistically significant association with the development of active tuberculosis was obtained for all factors studied (tobacco smoking: OR = 8.7, 95% CI 3.6-21.6, p = 0.01; chronic alcohol and narcotic intoxication: OR = 3.5, 95% CI 1.8-6.5, p = 0.001 and OR = 2.5, 95% CI 1.1-5.4, p = 0.026, respectively). In the group of patients with CD4 count above 200 cells/µL, there was a confident effect of smoking and clinically significant substance abuse on the risk to develop active tuberculosis, and the power of their effect increased: for tobacco smoking OR = 12; 95% CI 1,5-98,7, p = 0.012; for drug abuse, OR = 4.8, 95% CI 1.7-13.4, p = 0.002. The tendency of chronic alcohol intoxication providing impact on the risk to develop tuberculosis in patients with CD4 count above 200 cells/μl persisted, but there was no statistically significant relationship in calculating the odds ratio OR = 3.1, 95% CI 3.1–9.6, p = 0.082. The obtained data allow considering people living with HIV and possessing history of substance abuse as a group facing the high risk to develop tuberculosis in need close follow-up aimed to prevent tuberculosis.

The review analyzed the studies and meta-analyses devoted the treatment of multiple drug resistant tuberculosis in combination with antiretroviral therapy as a possible risk factor of adverse events and the worst outcomes of therapy. In total, the analysis included 18 sources from the Russian and English databases. Most of the studies did not reveal a confident relation between the simultaneous use of antiretroviral and anti-tuberculosis therapy with second line drugs and increased frequency of adverse events. At the same time, in the largest studies, as well as studies devoted to certain adverse events, the authors managed to prove the existence of such a connection. Data on the structure of adverse events also significantly differed in the results obtained by various authors. Most trials were conducted in African countries with a high prevalence of HIV infection.

The review presents the special aspects of bacillary excretion in tuberculosis patients co-infected with HIV and the yield of acid-fast smear depending on the CD4-cell count. Predictors of positive growth of Mycobacterium tuberculosis from sputum under negative microscopy in this category of patients are considered. The experience of different countries of the world on the effectiveness of various diagnostic algorithms for detecting tuberculosis in HIV/TB co-infection and the role of molecular-genetic methods in the diagnosis of tuberculosis are discussed. According to the data presented in the review, the yield of acid-fast sputum smear microscopy varies significantly, and depends on a variety of factors, including the immune status of the patient with HIV infection, the level of the laboratory service. The different yield of the smear microscopy in combination with the subclinical course of tuberculosis and atypical radiologic presentation in patients with HIV infection leads to a delay in diagnosis and to late initiation of antituberculosis therapy. The culture and the molecular-genetic methods of sputum examination increase the frequency of detection of the pathogen, however, the diagnosis of tuberculosis by culture can not be considered rapid in patients with immunodeficiency. Therefore, in the context of the continuing increase in the number of patients with co-infection, rapid, molecular-genetic methods for the detection of MTB DNA should be included in the algorithm for screening for tuberculosis of HIV- infected patients during their first encounter with the healthcare system.

The objective of the study is to investigate the specific course of pregnancy, perinatal outcomes and treatment results in HIV negative female patients.Subjects and Methods. Medical files of 109 pregnant tuberculosis patients were analyzed who were followed up in Krasnoyarsk Regional TB Dispensary no. 1 from 2010 to 2014.Results. The part of children prematurely born by mothers ill with tuberculosis was practically compatible with the overall national cohort of live-born children (6.8% in the analyzed group versus 5.7% in the national cohort for 2014). The part of children with congenital abnormalities born by mothers suffering from tuberculosis turned out to be twice lower versus the overall national cohort of live-born children (1.4% versus 3.0% in 2010 and 2.9% in 2014).The efficiency of the main treatment course in pregnant women without multiple drug resistant tuberculosis, of which 3.8 ± 0.3 months of tuberculosis treatment coincided with pregnancy was practically the same as treatment efficiency for the overall cohort of patients in Krasnoyarsky Kray (66.2% in the analyzed cohort versus 60.3-72.7% in the regional cohort for 2010-2014). In the pregnant with multiple drug resistant forms of tuberculosis, treatment efficiency was lower versus the regional cohort (30.4% in the analyzed cohort versus 41.1-60.2% in the regional cohort for 2010-2014).

The aim was to study the causes of death in HIV patients in the Novokuznetsk tuberculosis dispensary in 2016 (population is 550 thousand people; about 2% of population are HIV-positive). Materials and methods: Protocols of all autopsies of HIV-infected patients (n=221) performed in 2016 in the Novokuznetsk tuberculosis dispensary. Results: The mean age of the deceased was 37Ѓ}6,9 years. HIV and tuberculosis (TB) co-infection was in 83,3% of patients (n=184), HIV/TB and other opportunistic or severe somatic diseases – in 10,4% (n=23), non-tuberculous opportunistic diseases – in 6,3% (n=14). The new tuberculosis cases were in 71,1% (n=147), relapses – in 7,2% (n=15), chronic tuberculosis cases – in 21,7% of patients (n=45). Disseminated form prevailed among the cases of respiratory tuberculosis; generalized tuberculosis (3 and more localizations) occurred in 87,0% (n=180), tuberculosis meningitis was found in 17,9% (n=37). Positive fluorescent sputum microscopy was in 72.5%, sputum cultures on Loewenstein-Jensen medium – in 78,3% with HIV/TB. Primary multidrug resistance was detected in 60,7% (including in 5,8% of them with primary extensively drug resistance). Severe opportunistic infections or malignancies were in 9,2% of HIV/TB (n=19) and in 78,7% of non-TB patients (n=11). Data on the CD4 level was known in 68,8% of cases (n=152): the median count was 75,5 cells/μl; 38,9% of new TB cases (n=46) were diagnosed with HIV in time of TB detecting. Antiretroviral therapy was performed only 13% of patients (n=29). Conclusion: There is a need for the optimization of HIV detecting approaches and early initiation of antiretroviral therapy before the appearance of incurable opportunistic diseases, as well as for comprehensive TB prevention.

Goal of the study: to investigate the informativeness of tuberculous mycobacteria detection by various techniques and to analyze the intensity of bacillary excretion in tuberculosis patients depending on their HIV status.Materials and methods. 360 HIV patients were examined due to suspected tuberculosis. The diagnostic procedure included two consecutive sputum test for acid fast bacilli (AFB)/tuberculous mycobacteria by fluorescent microscopy, molecular genetic tests and culture on liquid and solid media. Tuberculosis was diagnosed in 178 (49.4%) patients. The comparison group included 354 tuberculosis patients with negative HIV status including 113 patients who underwent the same diagnostic procedure as those suffering from TB/HIV co-infection.Results of the study. AFB were more often detected by fluorescent microscopy in HIV negative tuberculosis patients compared to those with TB/HIV co-infection (32.8 and 24.2% respectively), and the sensitivity of the other testing methods did not differ. Scarce bacillary excretion was confidently more often registered in those suffering from TB/HIV co-infection and less frequently they had massive bacillary excretion detected by culture on solid media compared to HIV negative tuberculosis patients. The complete diagnostic procedure demonstrated better sensitivity in those with TB/HIV co-infection compared to tuberculosis patients with negative HIV status (87.1 and 71.2%).

The study presents the results of comparing the social status and the efficiency of TB treatment in pregnant women with or without HIV treated in Krasnoyarsk Regional TB Clinic № 1 in the years 2010–2014. It is based on a retrospective analysis of health cards of 133 pregnant TB patients divided into groups: Group 1 (TB), n=109; Group 2 (TB and HIV), n=24. More than a half of the women (51,3% and 54,1% accordingly) were new TB patients, the others had been previously treated for TB. A moderate immunodeficiency was more often detected in co-infected pregnant women (mean CD4+ lymphocyte count being 387 cells/ml), although in 4 patients the CD4 count was lower than 200 cells/ml. The registered rates of bacterioexcretion and lung disintegration were practically the same (57,7% and 58,3% versus 53,2% and 54,1% accordingly); MDR TB was diagnosed in 51,1% in Group 1 and in 60,0% in Group 2.Results: Patients of both groups had various social problems. However, the most aggravating medico-social factor among the co-infected women was active drug abuse during pregnancy (proved in 37,5%). The clinical course of TB in patients with HIV was severer, they more often developed acute forms of the disease. Preterm delivery was more frequent in TB/HIV cases (46,1% vs. 12,3%, p

Objective: To study the informative value of the detection of mycobacteria in blood with the cultural method in patients with suspected tuberculous sepsis and to determine the most significant clinical and laboratory criteria for testing. Materials and methods: The investigation to detect M.tuberculosis was fulfilled in 159 HIV-positive patients with suspected tuberculosis sepsis. Blood culture was completed with culture medium Myco/F Lytic Culture Vials and analyzer BACTEC 9050. Results: Mycobacteria were detected in blood of 19 patients (11,9% of all patients): in 18 patients the growth of М. tuberculosis complex was detected (25,3% of all patients with diagnosed tuberculosis) and in 1 patient it was Mycobacterium avium complex (0,6% of all patients). It was shown, that the probability of M.tuberculosis detection was especially associated with the severity of the disease, immunosupression (less than 100 cells/mkl), hemoglobin quantity less than 90 g/l (levels were determined through the seeking for the most significant cutoffs). It was not proofed, that meningoencephalitis develops more often in patients with proven bacteremia. There were no evident differences in detection frequency of mycobacteria in sputum between patients with tuberculous sepsis and without it.

The article describes the clinical case of TB/HIV coinfection in the pregnant woman and newborn. The discussion of the management tactics included main issues on which treatment success depended on: the right choice of chemotherapy regimen, correct decision on the time of delivery due to life-threatening conditions of the mother, timely diagnostics of tuberculosis in the newborn. It is necessary to develop cross-disciplinary guidelines by professional medical communities on the management of pregnant women with TB/HIV coinfection which will allow enhancing the quality of medical care to pregnant women and newborns at all stages of follow-up.

The increase in HIV patients manifesting clinical signs of sepsis requires up-to-date, rapid and reliable techniques for etiologic diagnostics.The analysis has included 53 publications related to various aspects of tuberculous bacteriemia, resources for its detection and their efficiency. According to the publications tuberculous mycobacteria in blood can be detected in HIV-positive patients with severe immune suppression (CD4: 17-18 cells/mcl) and presence of the following clinical and laboratory and X-ray signs: fever, severe anemia, paratracheal lymphoadenopathy, miliary dissemination. It is feasible to test the blood in order to detect tuberculous mycobacteria only in the very ill HIV positive patients in whom tuberculosis is suspected and it is impossible to collect sputum and there are no obvious signs of pulmonary lesions.The presence oftuberculous mycobacteria in blood isrelated to the high mortality level (up to 60%) and the immediate prescription of anti-tuberculosis therapy can reduce it. Antiretroviral therapy can reduce the chances of tuberculous sepsis development. Development and optimization of test systems for rapid detection of DNA of tuberculous mycobacteria in blood can be fairly promising for the diagnostics of the urgent tuberculosis.

Here is presented the clinical surveillance of course coinfection (and HIV / TB) process of a pregnant woman. In a retrospective discussion of medical tactics marked the main points of contention in the conduct of pregnant women with coinfection (HIV / TB), an analysis of the adequacy and the need for X-ray examination of the patient, the effectiveness of the treatment process coinfection process. The case demonstrates the ability of HIV-infected effectively treat tuberculosis and healthy baby female patient with active tuberculosis with timely and adequate combination therapy (antiretroviral and anti-tuberculosis).

The literature review describes the current state of the problem of the co-infection (HIV infection/tuberculosis) in pregnant women. Certain questions of tuberculosis detection and diagnostics in pregnant HIV-infected women were discussed. Approaches to treatment of drug susceptible and drug resistant tuberculosis in pregnant HIV-infected women were described with the reference to potential drug interaction. The literature review included the part devoted to specific diagnostics of congenital tuberculosis in children born by mothers with the co-infection. The need of further investigation of the actual issues of HIV/tuberculosis co-infection in the pregnant was highlighted.

The article presents the analysis of immediate and postponed outcomes of surgical treatment of tuberculosis spondylitis in HIV-infected patients; the relative risks of post-surgery complications have been estimated.

Comprehensive morphological examination of surgical and biopsy samples from 148 patients and autopsy specimens from 181 deceased persons was made to determine a correlation between the level of immunosuppression and the microscopic signs of tuberculosis in patients with HIV-associated tuberculosis (HIV/TB). A relation was found between the count of CD4+ lymphocytes and the predominant type of a tissue inflammatory reaction. Insidious granulomatous inflammation and a preponderance of alterative and exudative components in the foci of tuberculous inflammation suggested that a delayed-type hypersensitivity response that was typical of tuberculosis gave way to an immediate-type hypersensitivity response and reflected severe immune system dysfunction. The lack of responsiveness of the macroorganism in the virtually complete absence of CD4+ lymphocytes observed during autopsy examination led to the acute progression and generalization of tuberculosis, by affecting all organs and systems.

На фоне ВИЧ-ассоциированной иммуносупрессии диагностика туберкулеза представляет значительные трудности. По данным 2010 г., в Российской Федерации в структуре вторичных заболеваний у больных ВИЧ-инфекцией туберкулез составил 39% (по данным МЗ РФ, ф. 61) и лидировал среди причин смерти людей, живущих с ВИЧ (ЛЖВ), умерших от причин, связанных с ВИЧ-инфекцией (63,4% в 2010 г. по данным МЗ РФ, ф. 61). Следовательно, у лихорадящего пациента с ВИЧ-инфекцией фтизиатрическая настороженность врача любой специальности должна быть приоритетной в диагностическом поиске. Вместе с тем более чем у половины больных на поздних стадиях ВИЧ-инфекции клиническая симптоматика связана с другими вторичными заболеваниями, что значительно осложняет проведение дифференциальной диагностики туберкулеза у этих больных. Анализируя ошибки, допущенные врачами общей лечебной сети при диагностике диссеминированного туберкулеза легких на поздних стадиях ВИЧ-инфекции, И. Ю. Бабаева показала, что большинству пациентов был поставлен диагноз внебольничной пневмонии [3]. В результате анализа летальных исходов среди взрослых больных ВИЧ-инфекцией г. Москвы определено, что частота клинически не распознанных вторичных заболеваний (основным из которых был туберкулез) у пациентов, проходивших лечение в неспециализированных клиниках, составляла до 50% [26].