[The spectrum of primary drug resistance of Mycobacterium tuberculosis in patients with tuberculosis in relation to human immunodeficiency virus status]. / Spektr pervichnoi ustoichivosti Mycobacterium tuberculosis k lekarstvam u bol'nykh tuberkulezom v zavisimosti ot statusa po virusu immunodefitsita cheloveka.

AIM: To estimate the detection rate and spectrum of primary drug resistance of Mycobacterium tuberculosis (MBT) in patients with tuberculosis (TB) in relation to their human immunodeficiency virus (HIV) status in a region with high HIV infection rates (the Perm Territory) and to compare of drug-resistant MBT (DR-MBT) in patients with HIV/TB co-infection, by using phenotypic and molecular genetic testing (MGT) methods. SUBJECTS AND METHODS: The results of sputum bacteriological examination were analyzed in 178 HIV-infected patients and 354 non-HIV-infected individuals with a TB diagnosis made in the period July 1, 2014 to August 1, 2015. The diagnostic algorithm for all patients involved a duplicate sputum test for MBT by two techniques: fluorescence microscopy (FM) and inoculation into the Levenstein-Jensen dense culture medium. In patients with HIV/TB, the bacteriological examination was complemented with two more methods: detection of MBT DNA by a real-time polymerase chain reaction assay using the AmpliTube-RV system (Synthol, Russia); and inoculation into the Middlebrook liquid nutrient medium, by applying the automated BACTEC MGIT 960 system. RESULTS: In patients with HIV/TB, the sensitivity of FM proved to be lower than in those with TB (24.2 and 32.8%, respectively; p<0.05) and that of inoculations into the dense culture medium was comparable regardless of HIV status (60.7 and 57.1%, respectively; p>0.05). The primary drug resistance of MBT in patients with HIV-TB was higher than that in HIV-negative individuals (60.2 and 41.6%, respectively; p<0.05). The phenotypic method (inoculation into the Levenstein-Jensen culture medium) and MGT revealed their agreement for the resistance of MBT to rifampicin (the most clinically significant drug in the choice of treatment policy) in 88.5% of the patients with HIV/TB. CONCLUSION: In patients with HIV/TB, the sensitivity of FM for detecting acid-resistant mycobacteria was lower than in those with TB and that of inoculations into the dense medium was comparable regardless of HIV status.

[Impact of etiotropic therapy on the immune status of patients with HIV infection and tuberculosis].

AIM: To evaluate the impact of etiotropic therapy on the immunological efficiency of treatment in patients with HIV infection in relation to the presence of active tuberculosis (TB) and the baseline count of CD4+ lymphocytes. SUBJECTS AND METHODS: A total of 239 HIV-infected patients were examined and divided into 3 groups: 1) 103 HIV-infected patients with TB who received both anti-TB therapy (ATBT) and antiretroviral therapy (ART); 2) 46 HIV-infected patients with TB who did not receive ART during TB treatment; 3) 90 HIV-infected patients without TB who used ART for the first time. CD4+ lymphocyte counts were measured by flow cytofluorometry in all the patients before and 4 and 12 weeks after treatment. RESULTS: Analysis of an increment in CD4+ lymphocyte counts in the HIV-infected patients with tuberculosis showed that those who had very low baseline CD4+ lymphocyte counts (median, 78 cells/µl) were noted to have significant positive changes (median, +146 cells/µl) at 12 weeks of ART. Even without ART, effective ATBT in the patients with a well preserved immune system (> 350 CD4+ cells/µl) in turn resulted in a substantial increase in CD4+ lymphocyte counts (median, +187 cells/µl following 12-week ATBT). At the same time, 10.9% of the patients showed a decrease in the baseline CD4+ lymphocyte counts during progression or delay in the tuberculosis process, which required that ART should be promptly performed. CONCLUSION: The investigation of the time course of changes in the increment of CD4+ lymphocyte counts revealed a swifter response to ART as their rapid increment in patients with coinfection (HIV infection concurrent with TB) than that in those with HIV monoinfection. When the baseline CD4+ lymphocyte counts are over 350 cells/µl, the start of ART should be delayed until TB treatment is completed.

[The morphological characteristics of HIV-associated tuberculosis in relation to blood CD4+ lymphocyte counts].

OBJECTIVE: To investigate the morphological features of HIV-associated tuberculosis with different peripheral blood CD4 lymphocyte counts. MATERIAL AND METHODS: Intraoperative and biopsy specimens from 148 patients with HIV-associated tuberculosis were examined. Group 1 included 16 (10.8%) patients having a CD4+ lymphocyte count above 350 cells/µl; Group 2 comprised 38 (25.7%) patients having 200 to 349 cells/µl; Group 3 consisted of 94 (63.5%) patients with a CD4+ lymphocyte count below 200 cells/µl. Histological and immunohistochemical studies and a polymerase chain reaction assay were used. RESULTS: According to the predominant inflammatory phase, all analyzed cases were divided into 4 patterns of tissue responses: 1) typical productive granulomatous tuberculous inflammation; 2) obscure productive granulomatous inflammation; 3) a predominant alterative phase with the formation of pyonecrotic foci; 4) a predominant exudative tissue response with the development of amorphofunctional pattern typical of nonspecific inflammation. A relationship was found between the count of CD4+ lymphocytes and the predominant pattern of a tissue inflammatory response. A productive component of inflammation prevailed in Group 1; a mild productive response with the significantly obscure features of a granulomatous process was dominant in Group 2; alterative phenomena were noted in Group 3. Most patients (n=132, 89.2%) were stated to have an obscure granulomatous response (n=61, 41.2%), and a preponderance of an alternative (n=48, 32.4%) and vascular (n=23, 15.6%) components of inflammation. CONCLUSION: The magnitude of alterative and exudative components in the foci of tuberculous inflammation suggested that there was a change-over from a delayed hypersensitivity reaction that was typical of tuberculosis to an immediate hypersensitivity reaction and reflected severe immune system dysfunction.

[The efficacy and safety of a therapy regimen including raltegravir and a fixed dose combination of lamivudine and abacavir in previously rifabutin-treated patients with tuberculosis and HIV infection].

AIM: To evaluate the efficiency and safety of using raltegravir (RAL) twice daily in conjunction with a once-daily fixed dose combination of abacavir (ABC)/lamivudine (3TC) in patients with HIV infection and active tuberculosis who have not previously received antiretroviral therapy (ART) and have taken rifabutin as antituberculosis therapy (ATT). SUBJECTS AND METHODS: The efficiency of ART was evaluated in 28 patients from a change in HIV RNA levels and from an increase in CD4+ lymphocyte counts during 48-week treatment that had been completed by 15 (53.6%) patients. The main reason for therapy discontinuation was that the patients returned to the use psychoactive agents. RESULTS: After 24 and 48 weeks of ART, the level of HIV RNA reached the undetectable values (less than 50 copies/ml) in 81.25 and 75% of the patients, respectively (according to an analysis including the patients who had completed the study in conformity with the requirements of the protocol). In only 2 patients, the virological therapy proved to be ineffective, which was likely to be associated with noncompliance with drug therapy. Following 24- and 48-week therapy, the increase in median CD4+ lymphocyte counts was 70 and 208.5 per µl, respectively. The concurrent use of ART and ATT caused positive changes in the lung skiagraphic pattern in 92.9% of the patients and complete resolution of lung tissue infiltration in 71.4%. Mixed infection ended in a fatal outcome caused by a progressive tuberculous process in 3 (10.7%) patients, in 2 of them within the first 8 weeks of treatment. The concomitant use of ATT including rifabutin and an ART (RAL + ABC/3TC) regimen was safe since one patient was noted to have a RAL-related adverse event (AE) (an allergic reaction) and caused the patient to discontinue therapy. ATT was not discontinued because of AE in any case. CONCLUSION: The ART regimen containing RAL and a fixed dose combination of ABC/3TC for adult patients with tuberculosis concurrent with HIV infection who are on combined therapy using rifabutin for tuberculosis may be recommended for the treatment of this category of patients.

[The value of changes in CD8+CD28+ and CD4+CD28+ cells in patients with HIV infection concurrent with tuberculosis during treatment].

AIM: To study the proportion of CD8+CD28+ and CD4+CD28+ cells among the CD8+ and CD4+ lymphocytes and the changes in these indicators in patients with HIV infection/tuberculosis (HIV/TB) versus those with HIV infection and those with TB. SUBJECTS AND METHODS: One hundred and six persons were examined and included into 4 study groups: 1) 39 patients with concomitant HIV/TB; 2) 25 patients with HIV monoinfection without TB who had not previously received antiretroviral therapy; 3) 17 patients with TB without HIV infection; 4) 25 healthy individuals (a control group). RESULTS: CD28 expression was found to be much more reduced on the CD8 lymphocytes than that on the CD4 ones. This is likely to be due to earlier CD8 lymphocyte dysfunction in both the patients with HIV infection and those with HIV/TB although the CD4 cell is the basic virus target. CONCLUSION: The study of the proportion of CD8+CD28+ cells among the CD8 lymphocytes is of more informative value than the determination of that of CD4+CD28+ among the CD4 lymphocytes.

[Diagnosis of tuberculous pericarditis in patients with HIV-infection].

AIM: To study specific features of the incidence, course and diagnosis of tuberculosis pericarditis (TP) in patients with HIV-infection. MATERIAL AND METHODS: We analysed results of diagnosis of 304 primary patients with organ tuberculosis in combination with HIV infection treated in Moscow tuberculosis hospital N 7 in 2006-2010. CD4 lymphocyte count median in tuberculosis onset was 140 in 1 mcl, 63.2% patients had a baseline level of CD4 lymphocytes under 200 in 1 mcl. RESULTS: TP incidence in primary patients with tuberculosis and HIV-infection was 6.3% while in patients with tuberculosis of multiple locations--13.7%. Cardiac tamponade symptoms were registered only in one case. Pericardial effusion was classified as moderate and large in 68.4% patients. Patients with large effusion (more than 20 mm in isolation of pericardial leaves) have undergone diagnostic pericardiocentesis and, in some cases, microdrainage. Sensitivity of exudate test for M. tuberculosis DNA with use of polymerase chain reaction was 100%. CONCLUSION: Active surgical policy in massive effusion tuberculosis pericarditis in line with adequate antituberculosis and antiretrovirus therapy in HIV-infected patients results in rapid resorption of the effusion.

[Analysis of lethal outcomes in patients with newly-diagnosed tuberculosis of the respiratory organs in combination with HIV-infection].

AIM: To analyse lethal outcomes in patients with newly-diagnosed respiratory tuberculosis comorbid with HIV-infection depending on initial count of CD4+ lymphocytes. MATERIAL AND METHODS: Of 304 HIV patients with newly-diagnosed tuberculosis treated in Moscow Tubercusis Hospital N 7 in 2006-2010, 40 (13.2%) patients died. Tuberculosis diagnosis was made after detection of M. tuberculosis (MT) by different tests, MT DNA in different biological material, histological verification or by effectiveness of specific antituberculous therapy. Postmortem examinations were made according to the protocol. RESULTS: Significant differences were detected in patients with initial count of CD4+ lymphocytes less than 50 in 1 mcl. Specific CNS affection was found in patients with initial lymphocyte count CD4+ less than 100 in 1 mcl. Most of autopsy examinations registered generalized acutely progressive tuberculosis with multiple lesions of internal organs and lymph nodes (LN). Microscopy revealed obscure morphological picture of specific inflammation with prevalence of alternative-exudative tissue reactions in the absence of a productive inflammation component. Cases with submiliary dissemination which was invisible in macroscopic examination due to a bright picture of exudative tissue reaction (rare plethora of the lungs, alveolar and interstitial edema, perifocal inflammatory reaction of nonspecific reactive nature) and small size of the lesions. The comparison of clinical and autopsy diagnoses revealed that involvement of intrathoracic LN and miliary dissemination, according to autopsy, occurred much more frequently than shown by antemortem standard x-ray examination of the chest. CONCLUSION: It is strongly recommended to perform computed tomography of the chest in all HIV-infected patients with long-term fever but without visible alterations on chest x-ray.

[Experience in improving the microbiological diagnosis of tuberculosis in the Kemerovo Region].

Measures to improve the organization of microbiological diagnosis of tuberculosis and to upgrade its quality have been implemented in the Kemerovo Region. The regional reference laboratory has been reconstructed in accordance with the international standards. Inter-regional centers for microbiological diagnosis of tuberculosis have been set up on the basis of large tuberculosis treatment facilities. Sputum microscopy centers have been opened on the basis of general medical service. A multileveled system for surveillance of laboratories and their staff training has been established. The work done has significantly improved the coverage of those who are to be studied and the quality of microbiological diagnosis.