Development Of Opportunistic Diseases Research Articles

Pleural pathology in HIV-infected patients: features of morphological diagnostics

Background. The progression of HIV infection is accompanied by the development of opportunistic diseases, including pleural effusions of various origins. Morphological examination of pleura tissue in cases of pleural effusion serves as the basis for establishing the etiology of the pathological process and, therefore, the final clinical diagnosis. Objective – analysis of results of morphological diagnostics of pleura lesions in HIV-infected patients in comparison with other laboratory tests and clinical diagnosis. Methods. 103 cases of pleurisy of various origins were studied. Pleural biopsies were obtained by various types of minimally invasive diagnostic interventions with subsequent morphological examination. Results were compared with the available data of microbiological and molecular genetic studies of pleural biopsies. Results. At the time of hospitalization the preliminary clinical diagnosis was pleurisy of unknown etiology in 96,1 % of cases. A combined disease was diagnosed – hepatitis C in a third of all observations according to the results of laboratory tests. Due to routine staining with hematoxylin and eosin, tuberculosis lesions of the pleura were diagnosed in 59,2 %, the second most frequent was the diagnosis of nonspecific pleurisy, 20,4 %. According to the duration of the process, acute pleural tuberculosis was established in 19,7 % of cases, the subacute form of tuberculosis pleurisy – in 54,1 % of cases, and chronic pleural tuberculosis was established in 22,9 % of cases. In 17,5 % of cases, in order to clarify the etiology of pleurisy, additional histochemical staining for infectious agents was performed. The results of microbiological and molecular genetic studies were established in 76,7 % of cases. The greatest number of M. tuberculosis detection was obtained during the culture study of the biopsy material and exudates. When comparing the final clinical diagnosis and the level of CD4 cells in peripheral blood, it was found that in most cases (74,5 %) pleural effusions developed at low counts of CD4 cells, less than 350/l. Conclusion. Tuberculosis predominates in the etiological structure of pleural effusions in patients with HIV infection. Pleural tuberculosis can be the main secondary disease or be combined with pulmonary tuberculosis. In second place in terms of frequency of occurrence, nonspecific pleurisy was diagnosed as a complication of the main secondary disease. Pleural effusions develop when CD4 cell counts are low. Morphological diagnostics of pleural lesions is the main research method in the diagnostic algorithm of cases of pleural effusions of unknown etiology against the background of HIV infection.

Challenges in the morphological diagnostics of infectious lung diseases among HIV-infected patients: a case-series study

HIV-infection is a long-term infectious disease, characterized by deterioration of the immune system and it is often complicated by the development of opportunistic diseases, mainly of infectious origin. HIV-associated infections become generalized in the late stages of the disease and often may combine, that makes challenges in the diagnosis of these diseases. Differential morphological diagnosis of HIV-associated lung infections is quite complex. Most frequently, there is the need to differentiate between tuberculosis, bacterial or septic pneumonia, cytomegalovirus lung lesions, and deep mycoses. The aim. To demonstrate the expediency and necessity to apply special complex morphological methods in HIV-infected patients with secondary lung lesions using the series of clinical cases as an example. Materials and methods. The case series consisted of 7 cases with discordance between the clinical-radiologic, laboratory data and histological conclusions. Of these, there were 5 cases of life-time and 2 autopsy diagnoses. All the clinical and laboratory data of these cases were retrospectively analyzed, and a number of additional special histological examinations were performed. The Ziehl–Neelsen and fluorescent methods, Gomori–Grocot and alcian blue-PAS staining as well as immunohistochemical examinations were used for the detection of mycobacterial antigens with different antibodies to M. tuberculosis. Results. The case series of initial morphological misdiagnosis or indeterminate histological diagnosis was revealed among hospitalized HIV-infected patients. Clinical data did not provide an accurate diagnosis of pulmonary pathology. According to the traditional histological examination, a tuberculous process was diagnosed in 3 cases, a chronic granulomatous process – in 2 cases, but without specifying the etiology. In two cases of autopsy, pneumocystis pneumonia was suspected in combination with other infections. Additional morphological examination with using 2–6 special methods made it possible to determine the correct diagnosis. In 2 cases of provisional diagnosis of tuberculosis, invasive cryptococcosis and “pneumonia in a drug user” were revealed. Cryptococcosis and pneumocystis pneumonia were detected in 2 cases with an unspecified process. In the autopsy cases, the diagnosis of pneumocystis pneumonia was ruled out, while viral-bacterial pneumonia and tuberculosis associated with cytomegalovirus infection were detected. Conclusions. The presented factual material demonstrates the principal importance of using a comprehensive morphological examination in cases of lung inflammatory processes in HIV-infected patients. Clinical patient data, namely HIV-status at the time of diagnostic procedures as well as radiological and microbiological findings serve as a substantial aid in the diagnosis.

Development of opportunistic lesions in patients with HIV infection in the absence of pronounced immunodeficiency

Research objective. Statistical data concerning patients with opportunistic infections depending on parameters of immunity and the description of a number of clinical cases of development of opportunistic lesions in patients with HIV infection in the absence of the expressed immunodeficiency. Materials and methods. Medical records of the patients with HIV infection hospitalized in 2012-2015 in the Infectious Diseases Clinical Hospital No. 2 of Moscow, and the clinical cases of patients with development of opportunistic lesions with satisfactory indicators of the immune status. Results. The distribution of patients with HIV infection who had opportunistic infections, depending on the number of CD4+ lymphocytes at the time of development of the disease revealed a significant group of patients with a sufficiently large number of CD4+ cells. Statistical data on the development of various opportunistic lesions with different parameters of the immune status are presented. The authors describe a number of relevant clinical cases. Discussion. The possible causes of the development of opportunistic diseases and their recurrence in patients with HIV infection with a satisfactory amount of CD4+ lymphocytes are discussed. In the pathogenesis of this phenomenon are important not only quantitative but also qualitative parameters of immunity, as well as the characteristics of the causative agents of opportunistic lesions.

DIAGNOSTIC SURGERY IN HIVINFECTED PATIENTS WITH DAMAGE OF CHEST ORGANS

The current epidemiological situation in the world, characterized by a constant increase in the number of HIV-infected. The steady progression of HIV infection, even in the presence of antiretroviral therapy (ART), is accompanied by the development of opportunistic diseases. Tubercolosis most often affects patients with HIV infection, as the risk of their illness is 20–37 times higher. Basically, radiation tests and immunological tests are used for the diagnostic of tuberculosis. The main diagnostic criterion for establishing the diagnosis of tuberculosis is detection of the causative agent (Mycobacterium tuberculosis by bacteriological or molecular genetic method. Other diseases with respiratory organs, pleura, and hilar lymph nodes may also occur In patients with HIV infection, which requires differential diagnostic, including surgical methods. It is often necessary to resort to a biopsy of pulmonary tissue, pleura, and hilar lymph nodes to establish a diagnosis. Among surgical methods, the use of minimally invasive operations using endoscopic techniques is most justified. Purpose of the study. Study of safety and effectiveness of the use of surgical methods in the diagnostic of chest diseases in patients with HIV infection. Materials and methods. The results of 105 diagnostic thoracic surgeries in patients with HIV infection which were performed in Moscow Research andClinicalCenterfor Tuberculosis Control of Moscow city Department in period between 2014–2017 were studied. All patients underwent diagnostic surgical interventions. Minimally invasive methods were predominantly used. The obtained diagnostic material was subjected to morphological, molecular-genetic and bacteriological analysis. Results of the research. After surgical interventions in patients with HIV infection with pathological changes in chest organs, unclear etiology, diagnosis of tuberculosis was established in 74 (70,5%) patients, nontuberculous etiology of the disease was detected in 31 (29,5%). Differential diagnosis of chest diseases in patients with HIV infection is an integral part of the work of phthisiatrician, pulmonologist and infectiologist. Surgical interventions in HIV-infected patients do not create a significant risk of changes in the immune status, respectively, their performance is independent of the level of lymphocytes and produced even with severe immunodeficiency. The use of surgical methods in diagnostic of chest diseases is safe, effective and does not lead to a significant number of complications and mortality in patients with HIV infection, regardless of the initial immune status. In addition, in number of patients, the operation is not only diagnostic, but also therapeutic, allowing significantly shortening the duration of treatment, avoiding the appointment of trial therapy. The conclusion. In case of tuberculosis, morphological verification of pathological changes in combination with bacteriological and molecular genetic research of the operation material makes it possible to assign an adequate regime of antituberculous chemotherapy in accordance with the sensitivity of the pathogen. The establishment of non-tuberculous etiology of the identified changes, changes the routing of an HIV-infected patient from an anti-tuberculosis institution to a specialized medical organization of the appropriate profile.

Track B Clinical Science

BackgroundToll-like receptors (TLRs) are transmembrane receptors that activate cells of the innate immune systems upon recognition of pathogen-associated molecular patterns. The TLR4 is an essential component of the innate immune response to various microorganisms. We investigated the impact of TLR4 polymorphism on development of opportunistic diseases in HIV-infected patients.MethodsThe presence of TLR4 Asp299Gly single nucleotide polymorphisms (SNPs) was determined in a cohort of 180 antiretroviral treatment-naive HIV-1 infected patients and evaluated in relation to the occurrence of opportunistic infections. TLR4 genotyping was performed by real-time PCR.ResultsOne hundred sixty-five patients were homozygous for the wild-type genotype (AA); 15 patients (8,3%) were heterozygous for the Asp299Gly SNP (AG).TLR4 polymorphism was associated with more frequent development of the opportunistic infections, such as active tuberculosis (OR=3.27; 95% CI [1.21–10.29]), herpes zoster (OR=4.15; 95% CI [1.24–7.29]) and toxoplasmosis (OR=6.23; 95% CI [1.19–18.67]) compared with genotype AA.In addition, TLR4 SNP was associated with development of opportunistic diseases among individuals with CD4 cell count of>100 cells/mm3, compared with homozygous HIV-infected patients (OR, 5.25; 95%, CI [2.28–10.47]).ConclusionThis study suggests a greater risk of developing of active tuberculosis and other opportunistic infections in patients with the Asp299Gly TLR4 polymorphism.

Tolerability of antiretroviral therapy (HAART) in elderly age

Background The median age of people living with HIV/AIDS is increasing: while efficacy of HAART has reduced mortality and prolonged the life of patients, low perception of risk and new late diagnosis are related to infection in an elderly age. Most new late diagnosis are performed in older hardly immuno-compromised subjects; the development of opportunistic diseases complicates management of therapeutic strategies (drugs interactions, cumulative toxicities, hypersensitivity reaction), mainly in presence of comorbities. Most randomized clinical trials with new drugs tend to avoid the enrolment of >50 years patients with proper comorbities of old age. So the few data we can analyze come from observational cohorts. While it is well defined that older people are more adherent to treatment and achieved an adequate control of HIV-RNA viremia more frequently than younger although an incomplete immuno-reconstitution, the development of drug toxicity with higher frequency is controversial. Elderly people are more frequent to show reduced hepatic and kidney function, frequently have comorbities requesting new therapies with a higher pill burden and higher risk of drug interactions. Most antiretroviral drugs are metabolized by cytochrome system. Treatment may accelerate mitochondrial dysfunction, nucleoside reverse transcriptase inhibitors may contribute to muscle wasting. Some typical side effects of HAART such as body change and facial lypoatrophy could be more evident when associated with natural facial changes occurring with aging and modify negatively self perceived body image and relationship capacity. Age was also shown to increase the risk of renal tubular disease in association with tenofovir. Age is one of the major cardio-vascular disease (CVD) risk factors and the inflammatory component may contribute to this increased risk despite HAART efficacy. The risk of myocardial infarctions is increased in older treated HIV+ patients: metabolic abnormalities are more frequent at baseline and the treatment could increase the cumulative risk of CVD.

Natural history of opportunistic disease in an HIV-infected urban clinical cohort.

To determine the effect of contemporary clinical care on the natural history of opportunistic disease in an urban population infected with human immunodeficiency virus (HIV). Urban university HIV clinic. Retrospective and prospective observational study. 1246 HIV-infected patients with CD4+ counts of 300 cells/mm3 or less. Incidence rates and Kaplan-Meier estimates of the probability of developing opportunistic disease with time, distribution of the CD4+ counts at which opportunistic disease develops, survival after the development of opportunistic disease, and the association between preventive drug therapies and the occurrence of opportunistic infection. The most common opportunistic disease was Candida esophagitis, which had an incidence of 13.3 events per 100 person-years and a 3-year Kaplan-Meier probability of 0.30. Pneumocystis carinii pneumonia, Mycobacterium avium complex bacteremia, cytomegalovirus, and the acquired immunodeficiency syndrome dementia complex occurred at rates of 5 to 9 events per 100 person-years and 3-year Kaplan-Meier probabilities of 0.15 to 0.22. Toxoplasmosis, cryptococcal meningitis, herpes zoster, the wasting syndrome, and Kaposi sarcoma occurred at rates of about 2 to 4 events per 100 person-years and with 3-year Kaplan-Meier probabilities of 0.05 to 0.10. Non-Hodgkin lymphoma, M. tuberculosis infection, progressive multifocal leukoencephalopathy, and cryptosporidiosis were the least common disorders, with an incidence of about 1 to 2 events per 100 person-years and a 3-year Kaplan-Meier probability less than 0.05. Only the incidences of cryptococcal meningitis, secondary P. carinii pneumonia, and herpes zoster decreased (P < 0.05) between 1989-1992 and 1993-1995. Fluconazole use was associated with a decreased relative rate of 0.49 (P = 0.06) for cryptococcal meningitis and a decreased relative rate of 0.61 (P = 0.005) for esophageal candidiasis. Rifabutin use was associated with a decreased relative rate of 0.37 (P = 0.002) for M. avium complex bacteremia, and trimethoprim-sulfamethoxazole use was associated with decreased relative rates of 0.33 (P = 0.02) for secondary P. carinii pneumonia and 0.55 (P = 0.08) for primary P. carinii pneumonia. Candidiasis, herpes zoster, and M. tuberculosis infection first occurred at a median CD4+ count greater than 100 cells/mm3, but all other opportunistic diseases first occurred at a median CD4+ count less than 50 cells/mm3. Median survival after diagnosis varied from 35 days for non-Hodgkin's lymphoma to 680 days for herpes zoster. In the patients studied, the incidences of secondary P. carinii pneumonia, cryptococcal meningitis, and herpes zoster have declined in the past 5 years. The incidences of primary P. carinii pneumonia and Kaposi sarcoma appear to be declining compared with historical estimates. However, although these and other opportunistic diseases continue to be relatively frequent complications of HIV infection, they are first occurring at more advanced immunosuppression than in the past. Continued efforts are needed to develop effective strategies for preventing opportunistic disease in very advanced HIV infection.