1. Comparing shorter with conventional MDR-TB treatment in Uzbekistan 2-month culture conversion rates and treatment outcomes
P du Cros1, A Khamraev2, D Lister3, A Ronnachit3, C Berry1, J Greig1, N Parpieva4, M Tillyashaykhov 4, G Cooke5, S Dietrich6, T Pylypenko3, Z Tigay2, J Achar1
1 Médecins Sans Frontières (MSF), Manson Unit, London, UK; 2 Ministry of Health, Nukus, Uzbekistan; 3 MSF, Nukus, Uzbekistan;
4 Ministry of Health, Tashkent, Uzbekistan; 5 Imperial College, London; 6 MSF, Berlin, Germany
@dr_jay_a

2. Uzbekistan Included in WHO list of 30 high burden MDR-TB countries
MDR-TB burden
New cases 23%; Retreatment 62%*
Fluoroquinolone resistance 7.6%#
Injectable resistance 18.1%#
# Eurosurveillance 18:

3. Aims
To test for an association between treatment regimen (SCR or Conventional Care) and:
2-month culture conversion status, and
Treatment outcome months after treatment start
in patients with pulmonary MDR-TB

4. Short Course Regimen (SCR)
Single-arm prospective observational
Three districts
Started recruitment September 2013
Regimen: 4-6 HZECmMfxPtoCfz – 5 ZEMfxPtoCfz

5. Shorter Course MDR TB Regimen (SCR)
Inclusion:
Pulmonary MDR-TB
(MTBDR plus, Xpert® MTB/RIF, MGIT 960)
Exclusion:
History of treatment with second-line drugs >1 month
Resistance to fluoroquinolone or both Km and Cm, or XDR-TB
Leaving some text as 22 as easier to read – if 24 then makes slide more congested

6. Methods Comparison groups: SCR CC
recruited into prospective single arm study CC
Same programme, different districts, same time period
Received WHO-approved 20+ month regimen
Ethics approval granted by MSF and Uzbek ERB, and the retrospective analysis met the criteria of the MSF Ethics Review Board for exemption from ethics review

7. Methods 2 month sputum culture conversion Final Outcomes
2 negative sputum cultures >30 days apart
Final Outcomes
Evaluated months after treatment start:
CC Success: evaluated at end of treatment
SCR Success: evaluated 12 months after end of treatment

8. Baseline characteristics
CC (%)
(N=230)
SCR (%)
(N=102)
P-value
(χ2 or ranksum)
Sex – Female
108 (47.0)
54 (52.9)
0.31
Age (median, IQR)
29.4 (23.9; 42.8)
31.0 (24.0; 50.8)
0.36
Not employed
204 (88.7)
89 (90.8)
0.57
Reports heavy alcohol use
16 (7.0)
6 (5.9)
0.72
BMI <18.5
101 (43.9)
34 (33.3)
0.07
Has diabetes mellitus
8 (7.8)
0.77
HIV positive
0 (0)
1.00

9. Disease characteristics
CC (%)
(N=230)
SCR (%)
(N=102)
P-value
(χ2 or ranksum)
Has X-ray cavities
117 (51.1)
39 (41.5)
0.12
Baseline smear:
negative
108 (47.6)
46 (46.0)
0.18
scanty
25 (11.0)
10 (10.0) 1+
63 (27.8)
38 (38.0) 2+
19 (8.4)
3 (3.0) 3+
12 (5.3)
Baseline resistance*
Kanamycin
54 (28.1)
28 (27.5)
0.91
* Proportions exclude missing from denominator

10. 2-month culture conversion
2m culture conv (%)
Unadjusted OR
2m culture conv (95% CI)
Fully adjusted OR
P-value
(Wald)
Treatment group CC
109 (52) 1
SCR
61 (69)
2.09 (1.23; 3.55)
1.93 (1.08; 3.43)
0.026
Age (per increasing year)
0.98 (0.96; 0.99)
0.97 (0.96; 0.99)
<0.001
Sex
Male
77 (53%)
Female
93 (61%)
1.41 (0.89; 2.24)
1.60 (0.96; 2.67)
0.07
Baseline smear
Neg
84 (75%)
Scanty/1+
72 (55%)
0.40 (0.23; 0.69)
0.37 (0.21; 0.66)
2+/3+
14 (26%)
0.12 (0.06; 0.25)
0.12 (0.05; 0.26)
Small font – how to convey thi information in easily readabcle fashion?

11. Final outcomes Unsuccessful outcome (%)
Unadjusted OR of outcomes (95% CI)
Fully adjusted OR of outcomes (95% CI)
P-value
(Wald)
Treatment group CC
73 (31.7) 1
SCR
36 (35.3)
1.17 (0.72; 1.92)
1.17 (0.69; 1.96)
0.56
Age (per increasing year)
1.02 (1.01; 1.04)
0.009
Sex
Male
61 (35.9)
Female
48 (29.6)
0.75 (0.47; 1.19)
0.72 (0.45; 1.16)
0.18
Cavities on Xray No
50 (29.9)
Yes
55 (35.3)
1.27 (0.80; 2.03)
1.20 (0.74; 1.93)
0.46

12. Limitations Bias: Non-randomized
However, similar staff and same lab across both groups
Also, very similar models of care across both groups
Confounding
Potential for confounding from unmeasured variables

13. Conclusions
SCR treatment results in higher culture conversion by 2 months
Similar final outcomes despite significantly shorter treatment
Encouraging results from an established programme

14. Discussion
Context of high background rates of second line drug resistance and low HIV prevalence
Results may be generalizable to other former Soviet states
Shortened treatment could have positive impact on transmissibility, reduced programme work and reduced patient costs
RCT study results awaited with great anticipation

15. Acknowledgements Patients, doctors and nurses in Karakalpakstan
MSF field teams
Ministry of Health, Uzbekistan
Dr Nargiza Parpieva
Dr Mirzagalib Tillashaikov
Ministry of Health, Karakalpakstan
Dr Atadjan Khamraev
Dr Zinaida Tigay
MSF Team Uzbekistan
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