HIV and Tuberculosis in Eastern Europe
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2 HIV and Tuberculosis in Eastern Europe Daria N. Podlekareva Meeting Standard of Care for HIV and Coinfections in Europe Rome, November
3 TB notification rates (per ) European region 2012 ECDC/WHO Regional Office for Europe. Tuberculosis Surveillance and Monitorering in Europe. 2014
4 Dynamics of TB incidence and mortality rates in Russia (per ) Shilova et al Ann.N Y.Acad.Sci. 2001
5 Factors associated with TB increase in Eastern Europe Economic transition and decline Increase in unemployment, impoverishment, crime Malnutrition, crowded housing, alcohol, smoking Decline in public health infrastructure Deterioration of TB control service Severe drug shortages and interruptions in supply Delays in diagnosis and treatment Increased rates of progression to active disease Increased mortality rates HIV Epidemic Shilova et al Arinaminpathy et al. 2010
6 MDR-TB in Russian Federation (%) ,3 26,5 23,4 20,3 21,4 18,7 16,2 16,5 14,4 14,5 10,5 11,2 14,4 13 8,9 9,5 6,7 7,1 7,8 8,3 9,4 9,8 10,7 8, all cases of TB New diagn. TB Ministry of health Russia, 2010
7 Multi-drug resistant TB and Extensively drug resistant TB (MDR-TB and XDR-TB) Resistance New (n=156) Minsk Previously treated (n=68) New (n=934) Belarus Previously treated (n=410) Isoniazid Rifampicin MDR-TB Ofloxacin Injectable agents XDR-TB Skrahina Eur Respir J 2012; Skrahina Bull World Health Organ 2013
8 Risk factors of MDR-TB in Eastern Europe General population: Adjusted odds ratio (95% CI) Previously treated cases 6.1 ( ) Age < 35 years 1.4 ( ) History of imprisonment 1.5 ( ) Excessive alcohol consumption 1.3 ( ) Smoking 1.5 ( ) Unemployed due to disability 1.9 ( ) HIV-positive: Previously treated cases 7.9 ( ) Pulmonary (v. diss. disease) 2.5 ( ) History of imprisonment 2.1 ( ) Skrahina Bull World Health Organ 2013; Post J Infection 2014
9 A patient with TB from Eastern Europe A typical TB patient: Drug addict, alcoholic, and marginalised person who is also unwilling to be treated or resist treatment by all means Former prisoners and homeless people main sources of disease and the real breeders of TB TB physicians, Samara Oblast, Russia B. Dimitrova et al 2006
10 Management of Tuberculosis in Eastern Europe A large verticalized network of specialized institutes, dispensaries, hospitals, outpatient clinics, sanatoria and rural feldsher points In Russia, about beds designated specifically for treating patients with TB Long hospitalisation period poor infection control high levels of TB transmission among patients and staff Long monitoring after successful clinical treatment and of patients with inactive TB
11 Management of Tuberculosis in Eastern Europe Case-finding and diagnostic are based on mass population screening, fluorography, X-rays, TST and to a lesser extent bacteriology Classification of TB allows a definition of chronic TB Limited availability of 2 nd and 3 rd line drugs In addition to the standard chemotherapy, other treatments are commonly used: Surgical interventions Artificial pneumothorax Pathogenetic and immune-modulating therapy K. Floyd et al M. Mansfeld et al 2013 Personnal communication
12 HIV and HIV/TB epidemics in Eastern Europe
13 Dynamics of TB and HIV epidemics in Russia per population 100,0 90,0 80,0 70,0 60,0 50,0 40,0 30,0 20,0 10,0 0,0 HIV incidence TB incidence in general population
14 HIV+ per population TB per HIV+ TB among HIV patients in St.-Petersburg HIV TB among HIV Panteleev et al. 2011
15 Tuberculosis among HIV-positive patients: an international prospective observational study The TB:HIV Study Overall objective To prospectively study long-term clinical prognosis of HIV-positive patients with active TB disease across Europe, and temporal changes and regional differences
16 Clinical characteristics of 1413 TB/HIV patients at time of TB diagnosis Eastern Western Southern Latin Europe Europe Europe America P-value N = 844 N = 152 N = 164 N = 253 Age (median, IQR) 35 (31-40) 37 (32-48) 42 (33-48) 38 (30-45) <.0001 Gender (female, %) <.0001 Ethnicity (white, %) <.0001 CD4 count (median, (IQR)) 107 (35-254) 149 (35-360) 129 (38-315) 96 (35-289) 0.12 HIV+ more than 3 months before TB diagnosis <.0001 HIV treatment, cart (%) <.0001 TB Risk Group - IDU (%) < In prison in last 2 years (%) <.0001 TB in the past, yes (%) Current OST, yes 1 (%) <.0001 A.M.W. Efsen. HIV Drug Therapy, Glasgow 2014
17 Management of HIV/TB in Eastern Europe
18 % of responding clinics Organisational set-up of TB services: results from survey 100 Eastern Europe Western Europe p< HIV andtb service at same hospital HIV and TB treated by same doctor HIV and TB follow-up in same clinic Directly observed therapy OST available for IDUs M. Mansfeld, EACS 2013
19 Role of opiate substitution therapy: results from Ukraine Methadone maintenance therapy (MMT) was associated with 3-fold higher odds of 90-day retention on TB treatment compared with control group (adjusted OR: 3.05 (95%-CI ) Out of 109 in-patient TB clinics in Ukraine, only 11 provide MMT Morozova, Int J of Drug Policy 2013
20 Proportion of patients Diagnosis of TB and availability of DST results 100% 80% 60% 40% p < Presumptive TB Probable TB Definite TB without DST Definite TB with DST 20% 0% Eastern Europe N=844 Western Europe N=152 Southern Europe N=164 Latin America N=253 A.M.W. Efsen. HIV Drug Therapy, Glasgow 2014
21 Proportion of patients Anti-TB drug-resistance among patients with DST results within one month of TB diagnosis 100% 80% 60% 40% 20% Rifampicin resistant/ Isoniazid resistant (MDR-TB) Rifampicin susceptible/ Isoniazid resistant Rifampicin resistant/ Isoniazid susceptible Rifampicin susceptible/ Isoniazid susceptible 0% Eastern Europe N=243 Western Europe N=66 A.M.W. Efsen. HIV Drug Therapy, Glasgow 2014 Southern Europe N=89 Latin America N=61
22 Choice of empiric therapy in relation to prevailing resistance pattern In treatment of MDR-TB, WHO advises >4 drugs known/likely to be effective + pyrazinamide If possible amikacin, capreomycin or kanmycin plus a fluorquinolone should be core drugs Lange, for TBNET; Eur Respir J 2014; Falzon, Eur Respir J 2011
23 Availability of anti-tb drugs Reported unlimited access to 2nd and 3rd line anti-tb drugs 100 Eastern Europe Western Europe P< M. Mansfeld, EACS 2013
24 Proportion of patients 100% Susceptibility of empiric anti-tb treatment in relation to subsequent DST results 80% 0 active TB drugs 1 active TB drugs 60% 40% 2 active TB drugs 3 active TB drugs 20% 0% Eastern Europe N=298/830 Western Europe N=94/151 Southern Europe N=104/162 Latin America N=89/253 >=4 active TB drugs p < Active drugs calculated from comparing empiric anti-tb therapy and subsequently known DST results A.M.W. Efsen. HIV Drug Therapy, Glasgow 2014
25 Treatment succes among new lab-confirmed pulmonary TB cases in 2011 ECDC/WHO Regional Office for Europe. Tuberculosis Surveillance and Monitoring in Europe. 2014
26 Mortality among HIV+ patients with a TB diagnosis Eastern Europe: 33% Argentina, Southern and Central Northern Europe: 8-14% Podlekareva, AIDS 2009
27 Mortality among HIV+ patients with a TB diagnosis in Eastern Europe influence of MDR-TB F. Post, J Infection 2014
28 Mortality among HIV+ patients with a TB diagnosis in Eastern Europe influence of MDR-TB Adjusted Cox models: MDR RH: 2.28 (95%-CI ) Disseminated disease: RH: 1.99 (95%-CI ) F. Post, J Infection 2014
29 Management of TB and HIV in Eastern Europe Treatment for TB and HIV is under different services of Health Ministry and carried out in different hospitals by different specialists TB: Tuberculosis (Phthisiology) service HIV: Infectious disease hospitals IDU managed by Narcology service Opiate substitution therapy only limited or unavailable Prisons are under Ministry of Internal Affairs Limited level of collaboration and data exchange Poor outcomes Serious surveillance problems personal communication
30 A patient with HIV/TB from Eastern Europe Management history ID hospital MTB+ Specialised TB hospital Discharged TB dispensary for outpatient treatment AIDS Centre Consultation of ID doctor on HIV-status and cart LOST TO FOLLOW-UP Other challenges include (but not limited to): - limited availability of Opiate Substitution Therapy and harm reduction programmes - Limited social support
31 Actions to improve the situation with TB and HIV/TB in Eastern Europe There is a need for concerted actions to improve the situation including: Strong infection control to stop spread of TB/MDR-TB and HIV infections, intensified case finding Availability of rapid TB diagnostic and drug susceptibility tests for TB Adequate empiric TB-treatment and subsequent TB-treatment guided by results of drug susceptibility testing unlimited availability of all TB drugs Adequate treatment of HIV infection Unlimited cart coverage Treatment of concominent conditions (IDU and HCV) Accounting for local conditions Political will and commitment
32 Acknowledgement Centre for Health and Infectious Disease Research, Copenhagen Jens D. Lundgren Ole Kirk Anne Marie W. Efsen Maiken Mansfeld Eastern Europe Aza Rakhmanova Alexander Panteleev Elena Skrahina
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