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HIV-infection and Tuberculosis
in Russian Federation
Alexey V. Kravchenko
MD, PhD, Professor
Russia AIDS Federal Center
Vera N. Zimina
MD, PhD, associate Professor
Moscow City TB Center, Russia AIDS Federal Center
The growth of the cumulative number of reported HIV cases
among Russian citizens from 1987 to 2012.
721 264
800000
700000
600000
500000
400000
300000
200000
101 576
100000
0
1987
1989
1991
1993
The cumulative number of deaths
1995
1997
1999
2001
2003
2005
2007
2009
2011
2013
The cumulative number of registered HIV-infected persons, excluding deaths
According to the individual record of cases of HIV infection among the citizens of the Russian Federation
The number of new cases of HIV infection in the Russian
citizens in 1995 - 2012 years
90000
2012 y.: 56% - IVDU; 42% - Heterosexual
80000
70000
70453
62387
58286
58181
60000
50000
40000
54856
37773
30000
20000
10000
0
1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013
The number of new cases of HIV infection
According to the individual record of cases of HIV infection among the citizens of the Russian Federation
Dynamics of the number of HIV-infected patients who had the
secondary diseases and diagnosis of AIDS in the Russian Federation
120000
99548
100000
86811
80000
63424
53735
60000
44558
40000
34290
20000
0
62579
15229
16970
2673
2000
7443
2001
5767
2002
6016
2003
10197
2004
3051
2005
2006
HIV-infected patients who have secondary diseases
These forms of federal statistical number 61
4480
7772
2007
18183
29452
23435
11783
2008
2009
2010
2011
2012
The number of persons with AIDS
New cases of TB associated with HIV infection in the Russian
Federation (1999-2012) including the Federal Penitentiary
Service (FPS -2007-2012)
2012 y. - 12334
14000
The incidence of co-infection (TB/HIV)
2292 1896
12000
10000
1945
In 2012, among all new TB cases
9% were HIV-infected patients
Krasnoyarsk region – 30%
1949
1304
8000
1157
6000
4000
2000
271
0
310
576
833
990
1407
2926
3907
4828
6083
7304
8668
9547
10438
1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012
Identified in the resident population
Identified in FPS
These forms of federal statistical number 61
The number of patients with active tuberculosis with
HIV infection, who are under supervision (2002-2012),
Including FPS (2007-2012)
35000
2012 y. -29708
The incidence of co-infection (TB/HIV)
30000
25000
6123
5640
23054
24068
2011
2012
5225
20000
4370
15000
3600
2862
10000
5000
0
2454
3133
2002
2003
4506
2004
6850
9102
2005
2006
11431
13213
2007
2008
TB/HIV-patients among the resident population
These forms of federal statistical number 61
16405
2009
19738
2010
TB/HIV-patients in FPS
TB cases among HIV-infected patients:
• - 41.9% - were or are in prison institutions
• - 76.5% - were infected with HIV through
intravenous drug use
• - 23% -85% (depending on region) - are
registered with the drug dispensaries
• - 61.5% of them are screened for TB
Dynamics of the number of registered deaths among people
living with HIV in the Russian Federation
25000
20304
18473
20000
15888
14599
13123
15000
11159
8542
10000
9851
14899
15955
12740
10938
8547
6122
5000
2745
3252
3920
4948
1446
0
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
Of the registered died in the year
Of those who are under the supervision died in the year
These forms of federal statistical number 61
2010
2011
2012
Distribution of HIV patients accordingly the
reasons of death
In 2011, the deaths of people living with HIV from dying of diseases associated
with HIV - 39.8% from other causes - 60.2%
80%
68,7%
64,2%
60%
61,0%
60,8%
56,7%
40%
20%
10,7%
3,4%6,5%
11,4%
3,5%7,6%
16,5%
7,6%
3,6%
15,1%
8,3%
3,4%
12,3%
3,6%6,3%
0%
TB
2007
PCP
2008
Recurrent pneumonia
These forms of federal statistical number 61
2009
2010
The other secondary diseases
2011
Main directions of antituberculosis care for the
patients with HIV
• TB prevention in patients with HIV
early HAART prescription;
tuberculosis chemoprophylaxis
• Early tuberculosis diagnostics:
active fluorography;
clinical symptoms screening;
on the uptake
• Tuberculosis diagnosis confirmation:
modern complex of measures for the patients survey that could
help to diagnose tuberculosis signs and symptoms
• Treatment: antituberculosis therapy, HAART, treatment of another
secondary diseases
Detection of TB in HIV-infected patients
•
According to the Resolution of the Government of the Russian
Federation " On prevention of tuberculosis in the Russian Federation"
of 25.12.2001 y . №892 patients with HIV infection are subject to
preventive examinations fluorography 2 times a year
•
With decreasing CD4 + lymphocytes identify the role of FG loses its
significance
•
This is due to the fact that the manifestation of tuberculosis in HIVinfected patients is significantly different from the current start in TB
patients with intact immune system
Early tuberculosis diagnostics in
HIV-infected patients
*4,5,6
*4,5,6
*5,6
*1,2
*1,2,3
*1,2,3
0.80%
1.50%
7.30%
27.00%
15.80%
33.30%
99.20%
98.50%
92.70%
84.20%
66.70%
CD4<100
СD4:100-199
СD4:200-349
HIV-patients
Zimina V.N., Batyrov F.A., Kravchenko A.V., Klimov G.V., Vasilyeva I.A.,
Tuberculosis and lung diseases 2011.- №12.
СD4:350-499
CD4>500
On the uptake
73%
TB
Active fluorography
*- p<0.05
DISTRIBUTION OF CO-INFECTED (HIV/TB) PATIENTS
ACCORDINGLY THE COUNT OF CD4+CELLS
% 50
45
40
35
30
25
20
15
10
5
0
42.9
29.4
13.4
<100
100-349
350-500
CD4+ cells/mm3
14.4
>500
Complex of the morphological biopsy study at the patients
with HIV-infection
Microscopy
Cytological study
Microscopy
Hystobacterioscopy with the CillNielsen stunning
OBLIGATORY!!!
Immunohystochemistry
DESIRABLE!!!
PCR
Zimina V.N., MD dissertation.-2012– 44 с.
The proportion of patients with HIVinfection screened for TB in 2010
Of the patients passed dispensary
screening for HIV infection
86,7%
Of the patients who are registered
in regional AIDS-centers
75,0%
55,6%
These forms of federal statistical number 61
Of all patients
with HIV infection
Range of MBT Drug Resistance in TB and HIV/TB Patients Depending on the
Degree of Immunosuppression (Absolute Concentration Method)
DR Definition
HIV/TB
n
%
TB
р
n
%
Monoresistance
9
7,1
20
19,4
<0,05
Polyresistance
19
15,1
16
15,5
>0,05
MDR including XDR
37
4
29,4
3,2
21
0
20,4
0
>0,05
MDR + first-line drugs
12
9,5
7
8,0
>0,05
MDR + first- and
second-line drugs
25
19,8
14
13,6
>0,05
DR to А, К, Сар
16
12,7
11
10,7
>0,05
DR to Fq
9
7,1
1
1,0
>0,05
Total number of DR
patients
65
51,6
57
55,3
>0,05
Total
number
of
patients tested for DR
126
100
103
100
MDR-TB Rate in HIV patients depending
on the number of CD4 lymphocytes
35,4%
HIV/TB
CD4<200
19,2%
20,4%
HIV/TB
CD4>200
TB
Zimina V.N., MD dissertation.-2012.
PolyR
15%
MonoR
7%
Sens
48%
TB/HIV
preXDR
13%
MDR
30%
MDR (non
preXDR and XDR)
14%
XDR
3%
TB
pre-XDR
23%
PolyR
28%
MonoR
35%
MDR
37%
MDR (non
preXDR and XDR)
14%
XDR
0%
Zimina V.N., MD dissertation.-2012.
MBT Malty Drug Resistance in TB and HIV/TB Patients
(WHO, 2011 г.)
Estonia
Эстония
- Primary MDR MBT– 22%
- Secondary MDR MBT – 45,2%
- Primary MDR MBT in HIV/TB patients – 7,2%
- Primary MDR MBT– 16%
Ukraine
- Secondary MDR MBT – 54,4%
- Primary MDR MBT in HIV/TB patients – 23,8%
Russia
• Primary MDR MBT– 16%
• Secondary MDR MBT – 42%
• Primary MDR MBT in HIV/TB patients – ND
WHO PROGRESS REPORT 2011
Recommendations of the Russian Scientific Society
of infectious diseases, 2012
CD4-lymphocytes, cells/mm3
When to start ART?
<100
When the TB-therapy is well tolerated, as
early as possible (within 2-3 weeks)
attached ART
100–350
Within 2 months (possibly after intensive
phase of TB-therapy). By reducing the
number of CD4-lymphocytes <100 cells /
mm3 prescribe ART immediately.
>350
When the background of the number of
CD4-lymphocytes is <350 cells / mm3.
Attach ART after the main course of TBtherapy, regardless of the number of CD4cells (prevention of relapse TB)
Pokrovsky VV, Yurin OG, AV Kravchenko et al. Protocols of regular check-up and treatment of patients with HIV infection 2013 / / Epidemiology
and Infectious Diseases . Topical issues . - 2012 . - № 6 , Annex . – P.1- 28 .
Chemotherapy regimens for empirical treatment of TB and in
different types of drug susceptibility of M.tuberculosis (DST) in
patients with HIV infection
DST
Phase of TB chemotherapy
Intensive phase
Empirical
3 H Rb/R Z E [Str/Km/Am]
treatment or DS
The continuation phase
6 или 9* H Rb/R Е [Z]
H E (S)
3 Кm/Аm Rb/R Z Fq [E]
MDR
8Cm Fq Z Cs/Trd PAS Pt [ Km/Аm] [E] 12-18 Fq Z Cs/Trd PAS Pto/Eto [ E]
9 R/Rb Z Fq [E]
* - In tuberculous meningitis and osteo-articular tuberculosis
Abbreviations : H - isoniazid , R - rifampicin , Rb - rifabutin , Z - pyrazinamide , E - ethambutol
S - streptomycin ; Km - kanamycin , Am- amikacin , Pto - protionamid , Eto - ethionamide
Cm - capreomycin , Fq- latest-generation fluoroquinolones , Cs - cycloserine , Trd - terizidone ,
PAS – Pasco
J. Bartlett et al. Clinical aspects of HIV, 2013 (Russian edition)
The preferred first-line ART regimens in
patients with HIV infection and tuberculosis:
(The regimens of TB-therapy including Rifampicin)
• ZDV (TDF or ABC) + 3TC + EFV
• ABC/3TC or TDF/FTC + EFV
When the patient's body weight 60 kg or more daily
dose of EFV be increased to 800 mg/day.
Pokrovsky VV, Yurin OG, Kravchenko AV et al. Protocols of regular check-up and treatment of patients with HIV infection 2013 // Epidemiology
and Infectious Diseases . Topical issues . - 2012 . - № 6 , Annex . – P.1- 28 .
Alternative regimens of ART: When used in
the regimens of TB-therapy Rifampicin
• At the level of VL < 100000/ml - ZDV/3TC/ABC in a
fixed combination ( Trizivir ®)
• RAL 0,8 g ( 2 tablets ) x 2 times daily + TDF ( or ZDV)
+ 3TC
• MVC 600 mg 2 times daily + 2 NRTIs ( when applied
dose of rifabutin MVC - 300 mg x 2 times / day )
• When used in the regime of ART HIV PI/r must be
replaced by rifampicin , rifabutin (150 mg/day)
Pokrovsky VV, Yurin OG, Kravchenko AV et al. Protocols of regular check-up and treatment of patients with HIV infection 2013 // Epidemiology
and Infectious Diseases . Topical issues . - 2012 . - № 6 , Annex . – P.1- 28 .
Immunological efficacy of HIV-infection treatment based on
the increase of CD4-cells median
CD4-cells/mm3
600
500
196
400
300
200
78
100
0
before
treatment
581
440
394
288
228
+187 cells/mm3
193
224
+ 92 cells/mm3
4 weeks
+146 cells/mm3
Antituberculosis treatment + HAART
HAART
12 weeks
Antituberculosis treatment
Kanestri V.G., Zimina V.N., Kravchenko A.V., et al.,. HIV and Tuberculosis co-infection: analysis of safety and tolerabiloity// Infectious diseases.2012.- 10. № 3.; 5-9
Therapy and adverse events (%)
Azotemia
Granulocytopenia
TB-treatment
+ HAART
Anemia
Skin reactions
Gastrointestinal
ALT/AST
0,0%
5,0%
10,0% 15,0% 20,0% 25,0% 30,0% 35,0% 40,0%
Azotemia
TB-treatment
Granulocitopenia
Grage 1
Anemia
Grade 2
Skin reactions
Grade 3
Gastrointestinal
Grade 4
ALT/AST
0,0%
5,0%
10,0%
15,0%
20,0%
25,0%
30,0%
35,0%
40,0%
Azotemia
Granulocytopenia
HAART
Anemia
Skin reactions
Gastrointestinal
ALT/AST
0,0%
5,0%
10,0%
15,0%
20,0%
25,0%
Kanestri V.G., Zimina V.N., Kravchenko A.V. et al. //Infectious diseases, 2012.- V.10, N3.- P.5-9.
30,0%
35,0%
40,0%
The recommended chemoprophylaxis regimens of TB
in HIV-infected patients
Recommendations
WHO, 2011
CDC, 2011
Russia, 2013
Indications for use CP
Regime of CP
HIV (+) (regardless of the number of
Н - at least 6 months
CD4-lymphocytes, Mantoux test and the
availability of ART)
Mantoux test >5 mm
Н - at least 9 months
IGRA-test (+)
HIV (+) (regardless of the number of
Н - at least 6 months
CD4-lymphocytes, Mantoux test and the 3 months HZ/Е +3Н
availability of ART)
(prevention by
contact with TB
patients)
WHO policy on collaborative TB / HIV activities in 2012
J. Bartlett et al. Clinical aspects of HIV, 2013 (Russian edition)
Tuberculosis diagnostic and treatment
perspectives at the patients with HIV
Registration in Russian Federation Urinary test for the
detection of lipoarabinomannan (LAM) at the patients with
HIV-infection (test advances: sensitivity increases as soon as
immunodefficinecy progresses and low cost)
The possibility of diagnostic algorithm changing with
the using of different test combinations depending on the
patient immunosupression stage and hospital type
New antituberculosis drugs registration for the
treatment of tuberculosis with MDR