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inaugural opportunistic infection? / I. Perbost, B. Mala-fronte, C. Pradier [et al.] // HIV Med. - 2005. - Vol. 6 (4). -P. 232-239.
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13. Opportunistic infection among HIV seropositive cases in Manipal Teaching Hospital, Pokhara, Nepal / Dhungel B.A., Dhungel K.U., Easow J.M., Singh Y.I. // Kathmandu University Med. J. - 2008. - Vol. 6, No. 3, Issue 23. - P. 335-339.
14. Opportunistic infections and other AIDS-defining illnesses in Poland in 2000-2002 / R.B. Podlasin, A. Wiercinska-Drapalo, A. Olczak [et al.] // Infection. - 2006. - Vol. 34 (4). - P. 196-200.
15. Recurrent tuberculosis in HIV-infected patients in Rio de Janeiro, Brazil / Golub J.E., Durovni B., King B.S. [et al.] // AIDS. - 2008. - Vol. 22 (18). - P. 2527-2533.
16. The HIV-associated tuberculosis epidemic - when will we act? / A.D. Harries, R. Zachariah, E.L. Corbett [et al.] // Lancet. - 2010. - Vol. 375 (9729). - P. 1906-1919.
17. Trends in overall opportunistic illnesses, Pneumocystis carinii pneumonia, cerebral toxoplasmosis and Mycobacte-riumavium complex incidence rates over the 30 years of the HIVepidemic: a systematic review / L. Coelho, V.G. Veloso, B. Grinsztejn, P.M. Luz // Braz. J. Infect. Dis. -2014. - Vol. 18 (2). - P. 196-210.
18. Global tuberculosis control: Surveillance, planning financing [Електронний ресурс] / Geneva, WHO, 2006. - Режим доступу : www.who.int/tb/ publications/ glob-al_report/en.
ENGLISH VERSION: PROBLEM OF AIDS INDICATOR INFECTIOUS DISEASES*
Bugayenko N.S, Sergeyeva T.A. * Kiev City AIDS Prevention Center
"Institute of Epidemiology and Infectious Diseases named after L.V. Gromashevsky of the National Academy of Medical Sciences of Ukraine (Kiev)
Kiev, Ukraine, is experiencing high incidence of opportunistic diseases that rank first (around 90% on the average) in the structure of secondary AIDS-associated pathologies. In 2006-2012, TB was the most common opportunistic infection (71.65%), followed by bacterial infections (12.07%) and fungal lesions (5.08 %) Bacterial and fungal infections were mostly related to the sexual transmission of HIV, and TB - to the infection through injecting drug use. 57.1-59.0°% of patients with HIV/TB co-infection were in the terminal stage of HIV infection with a low CD4 count (< 200 cells/ml); 61.4% of them were injecting drug users. HIV infection in over 60% of patients was diagnosed when they had a manff-est immune deficiency and severe opportunistic infections, which was reducing the efficiency of ART. There is a need to improve the system of health care for, and monitoring of HIV positive individuals wtth a focus on a timely detection of the disease.
Key words: HIV infection, opportunistic infections, tuberculosis (TB).
Introduction
HIV infection does not have a clear clinical picture and is mostly manifested by AIDS-related conditions, such as opportunistic infections (OI), which are secondary diseases developed in patients with immune deficiency. Most frequent etiologic factors of OI include potentially pathogenic infectious agents that do not cause diseases in immune competent individuals, but they can also be caused by pathogenic infectious agents (such as M. tuberculosis). On the background of immune system suppression, HIV positive people develop various diseases including both OI and other conditions of infectious and non-infectious etiology, which, in their turn, have a significant impact on the life time and mortality of people living with HIV (PLH). Tuberculosis (TB) is of special importance among these conditions as today it is considered not only as HIV/AIDS related, HIV/AIDS-indicator, but also as HIV/AIDS-marker infection among certain populations [2, 5].
Tuberculosis remains a key cause of mortality among PLH. Globally, according to 2012 estimates, 13% (1.1 million people) of the estimated 8.7 million people living with HIV, had developed TB. Of 2.8 million people living with TB, who were tested for HIV markers in 2012, 20% were HIV positive. [10]. At the same time, HIV infection is the most important risk factor for TB infection and, even more, it leads to TB "revival" [16].
TB is the most common OI in some countries (especially developing ones or countries with transition economies); it is followed by oral candidiasis, Herpes zoster, cryptococcosis (cryptococcal meningitis), cerebral toxoplasmosis, cytomegalovirus (CMV) infection, etc. Significant reduction of the OI incidence among HIV positive people and changes in the spectrum of infectious agents have been observed in the developed countries thanks to the broad introduction of antiretroviral therapy (ART) and highly active antiretroviral therapy (HAART) since mid-1990s [9]. This year Coelho L. et. al, having analyzed the OI incidence among HIV positive people in different countries of the world have estimated that from 1982 to 2008 the levels of Pneumocystis carinii incidence have reduced, at an average, by 2.0-15.6 times; of cerebral toxoplasmosis - by 1.2-8.0 times; of diseases caused by Mycobacterium avium complex - by 2.4-25.8 times [17]. These data are extremely encouraging, as they provide evidence that OI can be controlled in HIV positive people, while underscoring the ongoing need in the timely diagnostic of HIV infection. However, there are significant differences in the burden and range of OI between economically developed countries and countries with limited resources, and the majority of evidence about the reduction of infection levels come mostly from the developed countries, which started to introduce HAART earlier and where HIV positive people have better access to specific
* To cite this English version: Bugayenko N.S, Sergeyeva T.A.. Problem of aids indicator infectious diseases / / Problemy ekologii ta medytsyny. - 2014. - Vol 18, № 1-2. - P. 39 -43.
Том. i8, N 1-2 2014 р. 39
diagnostics and treatment services [12, 14]. However, in spite of the HAART opportunities, OI still remain the factor of higher risk of morbidity and mortality for people living with HIV/AIDS, and the range of infectious agents of the most common OI varies in different regions. That is why there is need to identify the prevailing pathogens responsible for the development of OI disaggregated by regions in order to ensure appropriate treatment, care and management.
Study Goal. To assess the level of OI incidence and to identify the most common AIDS-related infections among HIV positive people in Kiev; to identify key factors contributing to the development of HIV/TB co-infection.
Study Objective and Methods
The study was conducted on the basis of the Kiev City AIDS Prevention Center (Kiev AIDS Center) for the period of 2005-2012. A comprehensive set of descriptive, estimative and analytical tools of the epidemiological research methods and mathematical statistical methods. To assess the prevalence of AIDS-indicator diseases among the patients of Kiev AIDS Center, the following official reporting materials of the MoH of Ukraine were used: Reporting Form №2 - HIV/AIDS, f. №502-1/o -«Registration Form of HIV infected person», f. №502-2/o - "Notice on changes in the Regisration Form of HIV infected person", f. №025/o - "Medical Card of outpatient patient", f. №003/o - "Medical Card of inpatient patient". Also, operational epidemiological data of Kiev AIDS Center were used for the study.
Unified functions of Microsoft Office Excel were used for statistical processing of the results. The incidence dynamics and long-term trends were defined with the methods of least squares. A relative percentage and its mean bias (P±mp), 95% confidence interval (95% CI) were also calculated. The power and direction of causal links were evaluated by the calculation of correlation ratio (r±mr); certainty of difference was defined by Student's t-distribution; the results were estimated on a confidence level that did not exceed (p < 0.05).
Study Results and Their Discussion
In recent years in Kiev, as well as in Ukraine in general, high incidence of OI and other AIDS-related diseases among HIV positive people have been observed. In 2005-2012 only and average of 2.59% (95% CI: 1.14 -4.05) of HIV positive people followed up by Kiev AIDS Center did not have these infections and this proportion was gradually declining. Almost 90% of secondary infections (95% CI: 88.82 - 90.98) had infections, mostly TB -71.65 % (95% CI: 67.67 - 75.64). Bacterial infections were second most frequent infections among Kiev AIDS Center patients - in 2006-2012 their average proportion amounted to 12.07 % (95% CI: 8.95 - 15.19), followed by fungal lesions - 5.08 % (95% CI: 1.94 - 8.23), cerebral toxoplasmosis - 4.66 % (95% CI: 2.35 - 6.97), PCP -2.90 % (95% CI: 1.38 - 4.42), herpetic infection - 1.65 % (95% CI: 0.50 - 2.80), CMV-infection - 1.22 % (0.67 -1.65) and other OI - 0.76 % (95% CI: - 0.52 - 2.04). Annually, fungal infections, in addition to disseminated can-didiasis, included reported cases of extrapulmonary cryp-tococcal infection, which, on the background of HIV progression, developed to generalized form; cases of pulmonary aspergilliosos were also reported. Most common bacterial infections in HIV positive people included pneumonia or sepsis with such key etiological factors as pneumococci, staphylococci, streptococci and, less frequently - esherichia.
Study of a general dynamics of infection reporting did not identify any clear trend of a significant change in proportion of various OI for the entire period of observation (Fig.). At the same time, it should be noted that the proportion of TB in the structure of AIDS-related infections had evidentially grown from 2005 to 2012 (p < 0.01), although an average long-term rate of growth indicated a stable trend (+0.07 %). At the same time, the proportion of bacterial infections had decreased (the declining rate was -3.87 % - a moderate trend; p < 0.05), except pneumocystis pneumonia, which in most cases is diagnosed in patients with HIV infection that was detected on IV stage, that is, among late presenters: its proportion has increased (+29.10 % - an expressed trend), but it can be explained by better diagnostic services. The proportion of fungal infections in the general structure of OI has evidentially decreased (the declining rate -23.41% -an expressed trend; p < 0.05). As far as other infections are concerned, the difference between the comparative relative indicators did not achieve any statistically significant level.
2012 2011 2010 2009 2008
2007 ■
2006
2005
0% 20% 40% 60% 80% 100%
■ Tuberculosis ■ Bacterial infections ■ Fungal infections
■ Toxoplasmosis ■ Pneumonia ■ Herpetic infection CMV-infection
Fig. Structure of AIDS-indicator infectious conditions in HIV positive people over time, 2005-2012
In 2013 the results of operational epidemiological analysis demonstrated that with the exclusion of tuberculosis all other OI was mostly associated with sexual (most frequently heterosexual) HIV transmission route: bacterial infections - 47.7 versus 40.5 % cases of infection through parenteral transmission; CMV infection - 75.0 versus 25.0% (p < 0.001), herpetic infection - 100%, candidiasis - 54.5 versus 36.4 %, cryptococcosis - 66.7 versus 0 %, pneumocystis pneumonia - 63.6 versus 36.4 % (p < 0.01), cerebral toxoplasmosis - 75.0 versus 25.0% (p < 0.05). HIV transmission route was not identified only in 2 OI cases (candidiasis and cryptococcosis); 5 cases of bacterial infections (11.9 %) were related to mother-to-child transmission of the infectious agent.
Clinical diagnostics of OI in HIV positive patients is complicated because their common manifestations (as-thenic syndrome, fever, lymphadenopathy, hepatosple-nomegalia) are often considered to be the signs of progression of the underlying condition. A broad range of clinical manifestations and frequent prevalence of inapparent infectious processes define the specific approaches to the diagnostic of this group of infections with the focus on laboratory methods and identification of the key diagnostic criteria.
It should be also noted, that the data presented here differ significantly from materials referred to in the literature published in the developed and less developed countries and exceed the levels of infection with OI infec-
tious levels. For instance, the reports of the US physicians indicate that 27.4% of patients with newly diagnosed AIDS had at least one OI, most frequently pneu-mocystis pneumonia - 12.2% and TB - 5.3 % [6]. The most common opportunistic infection among HIV positive people in Nepal was TB (30.4%), followed by candidiasis (14.3%) and pneumocystis pneumonia and Cryptococcus infections (3.6% each) [13]. Most frequently reported OI among HIV positive patients in Taiwan included candi-diasis, pneumocystis pneumonia and tuberculosis, while the number of these cases began to reduce significantly after the scaling up of HAART [9]. According to the data from Poland, five years after the introduction of HAART the AIDS incidence reduced and the most common OI among HIV positive people were fungal infections and TB [14]. So, today we are facing the situation, which is very similar to that in Sub-Saharan Africa and South East Asia in the period that preceded a broad introduction of ART.
These data confirm that today in Ukraine in general and in Kiev city in particular, tuberculosis is the most severe AIDS-related disease and it occurs in the process of HIV infection progression earlier than other OI, contributes to a faster development and progression of infection, development of multidrug-resistant forms and high
Some indicators of intensity of epidemic process of HIV infection,
mortality rates among HIV positive patients. In recent years the problem of TB in combination with HIV/AIDS has become a real threat to Kiev residents. One of the key negative tendencies of HIV/AIDS epidemic in the city is the growing number of new cases of HIV/TB co-infection. If before 2000 we registered only single cases of this co-infection, then in 2005 we officially registered 39 patients with HIV/TB co-infection and in 2012 their number grew almost tenfold (Table).
While assessing the intensity of epidemic process of this co-infection, one should note such extremely unfavorable factor as a quick rate of growth of the number of HIV/TB cases in the city of Kiev - an average long-term growth rate was +14.1% (an expressed trend) in 2005-2013. At the same time we observe a doubtful opposite correlation in the dynamics of active TB incidence in the city and HIV/TB incidence (r = -0.38), but a direct mean power ratio of correlation with HIV incidence (r = +0.63, mr = 0.21). So, we can presume that the growing number of HIV positive people with TB in the city is caused by HIV infection in the first place. According to the literature, an active form of TB develops in a HIV infected person 6-50 times quicker than in people, who are not HIV infected [18].
Table
tuberculosis and HIV/TB co-infection in the city of Kiev (2005-2013)
^^^^^^^ Years Indicato rs ^^^^ 2005 2006 2007 2008 2009 2010 2011 2012 2013
Number of newly detected HIV infections 1022 1146 1183 1258 1094 1077 1269 1302 1405
(abs. number)
HIV incidence (per 100,000 population) 39.1 42.4 43.4 46.8 40.0 39.4 45.4 46.1 49.0
Number of newly detected (all forms) of active TB (abs. number) 1228 1403 1256 1280 1023 950 1073 1143 1473
TB incidence () 46.8 52.9 46.9 47.4 37.6 34.6 38.9 41.2 51.8
Number of newly reported HIV/TB cases 39 107 179 226 241 230 284 309 302
(abs. number)*
HIV/TB incidence (per 100,000 population) 1.4 4.0 6.6 8.2 8.7 8.2 10.1 11.0 10.5
*based on the data in Form №2 - HIV/AIDS
This table demonstrates that in 2012 TB was diagnosed in 309 people with AIDS, which accounted to 67.7 % of all ADIS cases, including 231 cases of pulmonary TB (74.8 ± 2.5)% and 78 cases of extrapulmonary TB (25.2 ± 2,5)%. Extrapulmonary TB cases mostly included tuberculosis of nervous system (TB meningoencephalitis) - (9.7 ± 3.4)% and TB of intermediate glands - (8.1 ± 3.1)%; while 0.9% of patients were diagnosed with os-teoarticular tuberculosis. Among HIV positive patients with the newly diagnosed HIV/TB co-infection, (30.0 ± 2.6)% of patients were shedding M. Tuberculosis bacteria.
In 2013, for the first time in the period of observation, some reduction in TB incidence among HIV positive people was observed in the capital city in spite of the growing rates of both HIV and TB incidence among general population of the city. As in the previous year the proportion of people with HIV/TB co-infection among HIV positive people was significant - 63.8 % (in Ukraine -51.9 %), while the proportion of TB cases among patients with newly diagnosed AIDS had a declining trend (annual reduction rate - -5.9 %). Compared to the previous year,
the proportion of people with pulmonary TB in the general group followed up by Kiev AIDS Center has slightly increased (79.8 ± 2.3)% - and, correspondingly, the proportion of HIV positive patients with extrapulmonary TB had reduced - (20.2 ± 2.3) %. The latter, as in the previous year, were mostly infected with tuberculosis meningoencephalitis, TB of intermediate glands and osteoarti-cular tuberculosis. The number of M. tuberculosis bacteria shedding patients also increased - almost half of people with newly diagnosed HIV/TB co-infection.
Just for comparison: in Kazakhstan, TB also stands first on the list of HIV associated OI, but accounts for only 16% of the total number of officially reported HIV positive people [1].
Age structure and gender distribution in the group of patients with HIV/TB co-infection did not differ significantly in the general group of HIV positive people: in 2012, 69.5% were men and 30.4% - women. In terms of age, the largest proportion was in the age group of 25-49 patients - 93.8 %; 2.6% of patients belonged to the age group 18-24 years and 3.5% - 50 years and older. In 2013 the trends in the age and gender structure of the
Tom. 18, N 1-2 2014 p.
patients with HIV/TB co-infection were similar to the general group of HIV infected people, but the share of men had slightly decreased (to 64.4%) while the share of women increased (33.6 %). We consider this fact as an unfavorable sign that confirms the trend of more active involvement of women in the epidemic process [4]. In terms of age, most cases were found in the age group of 25-49 years.
According to the materials for 2012, artificial parenteral transmission of HIV through drug injections was prevailing in the structure of HIV transmission routes -230 people were infected parenterally and 79 people -through sexual transmission - (74.4 ± 2.5)% versus (25.6 ± 2.5)% (p < 0.01). In 2013, HIV transmission among co-infected individuals was mostly associated with injecting route -198 versus 131 people, who were infected through sexual contacts with HIV positive people, that is, respectively, (60.0 ± 2.7) % and (39.7 ± 2.7) %. However, this difference has slightly reduced compared to 2012 and was not reliable, which confirms the general trend towards the beginning of redistribution of the prevailing HIV transmission routes in the city from parenteral to sexual transmission [3]. In one case (0.3%) HIV was transmitted from mother to child.
In 2012, CD4 count of 57.1 % living with HIV/TB co-infection (n = 293) was less than 200 cells/ml, which is a confirmation of the terminal stage of HIV infection. According to the studies conducted in 2013, the number of people with terminal stage of HIV infection (on the basis of CD4 count) among these patients increased to 59.0 ± 2.9%. At the same time, 16.0 ± 2.1% of patients had CD4 count within 50-100 cells/ml and 25.9 ± 2.6% - < 50 cells/ml. Also, it is well known that CD4 count is a 'surrogate marker' that reflects probability of development of other OI.
The largest number of patients with HIV/TB co-infection on the terminal stage of HIV infection was found among IDUs - (61.4 ± 2.8)%; (34.8 ± 2.7)% were infected through heterosexual contacts with HIV positive people and the rest (3.8 ± 1.1)% - through homosexual contacts. It is common knowledge that injecting drug use is increasing the negative effect of HIV on the immune system (as well as co-infection with viral hepatitis B and C and other co-infections).
In 2011, Kiev AIDS Center conducted an operational research to identify the place of TB in the mortality structure of PLH on the basis of analysis of 150 medical cards of HIV positive people, who died in the previous year. The research found that a significant proportion of the deceased - (75.3 ± 3.5)% - were HIV infected through injecting drug use; (55.3 ± 4.1)% of patients were enrolled in care on the stage IV of HIV infection, and (23.3 ± 3.5)% had stage III; (19.3 ± 3.2) % of patients lived less than a month after enrollment; in (68.0 ± 3.8)% of patients TB was diagnosed intravitam and 60.7 ± 4.0% lived less than 1 year after enrollment; (12.0 ± 2.7)% of those who died were receiving isoniazid prophylaxis of TB. Among people, who died with HIV/tB co-infection, (44.0 ± 4.1)% were diagnosed with pulmonary TB, (10.0 ± 2.4)% had miliary and extrapulmonary TB; (2.0 ± 1.1)% had MDR TB and (32.0 ± 3.8)% were newly diagnosed TB patients; (34.7 ± 3.9)% of patients were receiving ART. Depending on the stage of HIV infection, an average life time of people with HIV/TB co-infection since the moment of enrollment was 4.3 years on stage I; 3.1 years on stage II; 2.3 years on stage III and 5.6 months on stage IV.
According to the statistical reporting forms (Form №33-healthcare), the number of TB patients who died of HIV related disease in Kiev is growing in both absolute figures and relative indicators. Starting from 2006 and till 2013 their number in the city has grown from 67 to 99 -
from 2.5 to 3.5 cases per 100,000 population with an average long term growing rate of +5.27% (an expressed trend), while the growth of the number deceased in 2013 was +29.6% compared to 2012. When HIV positive patients have TB, the extremely high mortality rate is related to an untimely diagnostic and inadequate treatment of TB, multi- and extra-drug resistance of M. tuberculosis. In 2013, according to the data from Form №2 (HIV/AIDS), 14.0% of patients died directly of TB, while the overwhelming majority (76.9 %) - of co-infection and around 9.1% - of causes that were not related to HIV/AIDS (drug overdose, suicide, accidents, etc.). According to the specialists of Pavlodar Oblast AIDS Prevention Center (Republic of Kazakhstan), TB was a direct cause of death for 40.2% of co-infected people, and the life duration with co-infection was following: up to a year - 40%, up to 2 years - 28.8%, up to 3 years - 11.9%, up to 5 years - 3.4%, 6-8 years - 5.1 % [1].
ART is the most important component of HIV/TB management as it helps to reduce the risk of mortality in patients with co-infection by 64-95 % [15]. Besides, the specific therapy also plays a big role in the prevention of co-infection, reducing the risk of its development by 67% at an average [8]. According to the literature, today OI incidence in HIV positive people, including TB incidence, is mostly related to late diagnostic or late initiation of ART, and it is considered to be one of the most complicated aspects of HIV epidemic [7, 11]. Also, one should not forget about the lack or poor adherence to the therapy, which leads to virological failures and disease progression. Lack of adherence is associated with such factors as a low educational level, young age, unemployment status, alcohol abuse, and drug use - that is, mostly social and economic factors. And, finally, another important factor is multiple resistance to antiviral medicines.
In spite of an ongoing scaling-up of access to specific treatment in Ukraine and Kiev, opportunistic infections remain the main cause of deaths among HIV positive people. High incidence and mortality among patients with OI have their underlying causes: a significant number of HIV positive patients do not know their status and thus turn to health care services late, in the very severe condition, when OI serve as indicators of their disease. Today over 60% of new HIV diagnoses in the city are made on the background of expressed immune deficiency and severe OI conditions. At the same time, according to the literature, late detection of HIV infection (e.g., approximately 6 months before the AIDS diagnosis) increases the risk of OI overlay by 3.5 times compared to people, who were diagnosed earlier and offered a respective therapy [6]. Data of the analysis of newly diagnosed TB cases in 2012-2013 demonstrate, that risk of TB development in patients with HIV infection is the least if they receive health care services, and late diagnostic of HIV infection leads to TB infection in most cases.
HIV positive patients under follow up at the AIDS Center do not always receive ART due to a number of reasons (low adherence, psychosocial factors, etc.); not all individuals, who receive ART, can achieve an adequate virological and immunological response.
Summing up the results of this work, we believe that it would be expedient to share the recent data of international experts: among 41 countries with a heavy burden of HIV and TB co-infection in 2004-2012, Ukraine (together with Angola, Brazil, Congo, Indonesia, Lesotho, Mozambique, Sierra Leone, South Africa, Sudan, Togo, Viet Nam and some others) was in the last third group of countries with a declining number of TB related deaths among PLH (less than 25%). At the same time, the global goal is to reduce the number of TB related deaths among PLH at least twofold (< 250,000) by 2015. But we would like to conclude with the more optimistic data - in 2012
only four countries including Ukraine from the above mentioned list of priority countries managed to achieve ART coverage among HIV positive people living with TB at the level of at least 50% [10].
Conclusions
1. In Kiev, high incidence of OI that account for at least 90% of all AIDS-related secondary infections is observed among HIV positive people in recent years.
2. Tuberculosis is the most common OI in HIV positive people and in 2012-2013 it accounted for over 65% of all newly reported cases of HIV infection. Pulmonary TB is the most frequent form in co-infected individuals; extrapulmonary forms include tuberculosis meningoen-cephalitis, TB of intermediate glands and osteoarticular TB. The number of patients with M. tuberculosis bacteria shedding is growing.
3. Bacterial infections (12.07%) prevail in the structure of other OI, followed by fungal infection (5.08%), cerebral toxoplasmosis (4.66%), pneumocystis pneumonia (2.90%), herpetic infection (1.65%) and CMV-infection (1.22%).
4. Adversative trends are observed in the dynamics of HIV/TB incidence and TB cases among the city population, and one-way development of the epidemic process of HIV/TB co-infection and HIV infection.
5. Over 60% of patients with HIV/TB turn to health services on the later stages of infection process development. In 57.1-59.0% of patients with HIV/TB diagnosis the number of CD4 lymphocytes does not exceed 200 cells/ml, which is an evidence of the terminal stage of HIV infection. The majority of patients with HIV/TB in the terminal stage are IDUs (61.4%).
6. To ensure timely diagnostics and treatment of TB there is a need to improve health services to, and monitor HIV positive people. Timely diagnostics remains a corner stone to settle this issue.
Prospects for further studies
Further efforts are needed to improve the system of epidemiological surveillance of OI in HIV positive people on the regional levels, taking into consideration all integral components, such as territorial characteristics of the epidemic process, immunological characteristics of the patients, viral load, etc. Studies that are focused on the determination of the epidemiological contribution of the patients as the sources of dual infection should be specifically developed.
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