 Thank you very much and now you get to see me be more nervous than the other presenters. It's a pleasure to be here this morning to present on behalf of my colleagues in MSF and in the Uzbekistan Ministry of Health. I'm going to be talking today about multi-drug resistant TB, resistance to the two best first line drugs that we use to cure TB normally in six months. And up until recently that conventional care has taken more than 20 months of treatment according to international guidelines, with eight months of daily painful injections, treatment that causes many side effects within some countries up to one third of cured patients going deaf, not to mention 10% having a risk of psychosis, risk of kidney failure and many many other side effects. This is very difficult to take treatment and at the end of it all we hear the reports from WHO 52% success rate and more than a half a million people are getting acquiring multi-drug resistant TB every year. So it's on that background that MSF and the Uzbekistan Ministry of Health thought can we do something different and we actually took some evidence from this region and tried to apply it in Central Asia. For those who don't know Uzbekistan is one of the 30 high burden multi-drug resistant TB countries and it has rates of 23% of MDR TB amongst new cases who've never had tuberculosis before with high rates of second line drug resistance as shown here and for those who are interested CATG mutation is more than 90% of cases of MDR TB. What I'm going to talk to you today is very briefly about two studies that we've conducted looking at testing for an association between comparing the shorter MDR TB treatment regimen with conventional care and we're going to be looking at two month culture conversion status as an interim outcome to look for any differences and also comparing the two groups at 20 to 24 months. The shorter regimen is 9 to 11 months it was first done in Bangladesh and has reported success rates of more than 80% and now in subgroups of MDR TB it's advised by WHO as policy as one of the regimens that can be used and data from this study and from several other studies was included in a meta-analysis to inform WHO policy. But this is really the first actual direct comparison of this regimen with conventional care. So the shorter MDR TB regimen was a single-arm prospective study that we set up in three districts in Karakor-Pakistan and Uzbekistan and we started recruitment in September 2013. I've put the WHO abbreviations but just to make sure we're all on the same page this is four to six months of high-dose isonized pyrozinamide, ethambutol, capriamycin or if sensitivity to canamycin was shown then we used canamycin which is the injectable agent. Moxifloxacin at 400 milligrams so standard dosing, proteanamide and clofazamine for the intensive phase and in the continuation phase five months of five drugs pyrozinamide, ethambutol, moxifloxacin, proteanamide and clofazamine. So a slight difference to a modification from the Bangladesh regimen with moxifloxacin at standard dose, proteanamide throughout the whole treatment. The inclusion criteria in this single-arm study was pulmonary multi-drug resistant TB and the exclusion criteria was a history of treatment with second-line drugs for more than one month or confirmed greater resistance either to fluoroquinolones or to both injectables canamycin and capriamycin or extensively drug resistant TB. Now we did a single-arm study and it's after the fact of doing the study that we decided to do a comparison so keep that in mind for the limitations but basically what we were able to do because within the same program we had another 13 districts where we were using WHO guidelines with conventional care so we've done a comparison of the patients treated with the short course regimen in the three districts versus patients from a retrospective database using the same inclusion exclusion criteria who were treated with the conventional treatment of 20 plus months during the same time period in the program and we're looking at the outcomes as I mentioned two months sputum culture conversion which is defined as two negative cultures more than 30 days apart and for final outcomes for the conventional care group we use WHO standard definitions at the end of treatment which is usually between 20 to 24 months and for the short course regimen we use those who we evaluated them 12 months after they'd finished treatment so after the 9 to 11 months 12 months means 21 to 23 months after starting treatment so this is the baseline characteristics and what you can see I'll point out the there's a lot of the numbers here that the key points are that in the conventional care group we had 230 patients and in the shorter regimen we had 102 to compare and mostly they were equally matched there was no statistically significant differences but you will keep in mind that the conventional care group had a higher proportion with 43% having low body mass index compared with the shorter course regimen only 33% there were no HIV co-infected patients in either group which is consistent with this program and the area in Uzbekistan where rates of HIV are incredibly low in terms of the baseline characteristics are slightly more around half of patients had cavities on their chest x-ray at baseline in the conventional care group baseline sputum smears were similar between the two groups and baseline resistance to kanemarsan was also similar about approximately a third in each group so what we did was an analysis using univariate and then multivariate logistic regression and what I'm going to present is the multivariate logistic regression there's a lot of numbers here and the key point about a multivariate logistic regression is we're trying to answer the question when we account for the other likely confounders how did the short course regimen compare with the conventional care so I've highlighted on this slide looking at the two month culture conversion that actually at two months after adjusting for the other key factors the there was a nearly two-fold increased odds of having converted having a negative culture so this means that two months on on this measure the patients in the shorter course regimen are doing better overall than the conventional care as a group the the model that we've used is a forward stepwise model including parameters that we decided a priori which is age and gender and any factor which caused more than 10% difference in the adjusted odds ratio secondly when we come to the final outcomes and I would say that this is still preliminary data because some of the patients we're waiting for their final microbiological outcomes but we have used a conservative approach whereby if patients don't have their final outcomes then we've excluded them from the analysis at the moment in this comparison adjusting for other factors including cavities on x-ray the adjusted odds ratio there was no significant difference between the shorter mdr tb regimen arm and the conventional care arm so as I mentioned there are some limitations so this is non randomized studies so there may be unmeasured confounders that could account for some of these results however we do think there's value in the fact that this was both districts within the same program same guidelines similar support for patients and similar training same models of care so in conclusion in this analysis the the shorter mdr tb regimen showed higher culture conversion by two months when adjusting for other measured co co confounders and there were similar final outcomes despite significantly shorter treatment so what does that mean it means for this sub group of patients actually instead of giving them nearly two years of treatment we can achieve similar results at two years but they only take treatment for nine to eleven months can you imagine being a patient and only having to take half the treatment time that's quite incredible and I think this gives further strength to the WHO recommendations about use of this regimen this is in a particular context with high background rates of second-line drug resistance but I think this is relevant evidence to this region in southern Asia which also has high rates of second-line drug resistance in mdr tb cases there may be relevance in the findings to transmissibility and certainly for programs that use culture conversion as a discharge criteria from hospitalization that may be a benefit to patients although as MSF I would say we are in our programs pushing for starting treatment ambulatory from day one which was done in this study we also must I think wait for the randomized control trial the stream study which should have results out next year which will answer many of the questions I'm sure you're going to ask me and I can only answer partially today so thank you to my colleagues to the staff in Uzbekistan and the patients yes yes please first and then second what has happened to the mic now suddenly they were all working no no no please okay use my so my name is yogish I'm Epidomologist in Manipur project can speak a little louder please I'm yogish Epidomologist in MSF Manipur project my question is have you consider analysis like previous treatment in the analysis part so and is there any mox you using moxibloxacin so we have you see any QT interval prolongations because it's high dose of moxibloxacin is so and you buy your thing I understood that there is a lot of confusion in the shorter demand earlier but have you have come across any support and reversion okay excellent question so three questions in there I'll try and answer them all and bear in mind that since the organizers kindly asked me to present two studies in the time of one I haven't gone through everything in terms of measured confounders we did look at past treatment diabetes HIV age gender particular resistance patterns to Canemison pyrazine amide and probably a couple of others as well that we had measured and those did not seem to make any difference of course there are other things in there that we didn't have good data on things like smoking which could have had an impact and there may be other unmeasured confounders the the third question was around did we see any reconversion so yes so one of the things I didn't go through is the the failure rate so using a failure definition that includes either having to change drugs because of adverse events or to having to change because of failure of conversion or of reconversion then what we did see was quite a high failure rate and a much lower loss to follow-up rates so the failure rate is 20% for this regimen which is quite high and something that we're still looking at but in terms of reconversion actually most of the cases were failure to convert rather than reconversion but we did have a couple of cases of reconversion moxifloxacin we haven't looked in the conventional arm we're not able to tease out those who got moxie up front versus levo and whether that made a difference the other question that we have with our results because the success rate is lower than what's been achieved in some other cohorts is is the lower dose of moxifloxacin responsible is it that we use capria myosin up front is it that there's just higher resistance rates and we're not able yet to tease that out that's my question the conversion Bangladesh regimen by Vandean in this regimen I find moxifloxacin is normal dose and the prosinamide is being used in the contravention phase also so what was the reason for having this change compared to the to the conventional regimen okay thank you so the reason we modified the regimen is we were very concerned that while we were taking evidence from Bangladesh how would it apply in a context where we knew we had quite a lot of second-line drug resistance and we had a high cat gene mutation rate so the pyrazinamide resistance is between 50 to 70% depending on which year of our cohort we look at what we decided to do was to put proteanamide throughout the whole regimen the downside of that of course is risk of side effects which may worsen your results as well with loss to follow-up I guess the second thing is we chose not to use moxifloxacin at a high dose as recommended by WHO because at that stage there was actually no data around QT safety we've got a separate analysis looking at QT safety from this cohort and what we've seen at one month with the standard dose of moxifloxacin is a median of 18 milliseconds of prolongation so longer than what's been reported for moxifloxacin alone so there is still some concern that there's not much safety data in fact I'm not aware of any safety data of moxifloxacin at high dose combining with chlophazamine and risk of QT or Torsard but we didn't see any episodes of Torsard or patients having to stop because of prolonged QT okay next question please somebody at the back row already answered okay yes yes you please Allen from MSF I think in many countries you work there's a higher HIV prevalence and how do we see the results of this study useful in a place with or are we trying looking at it in places with a higher HIV prevalence rate okay so there is a study that is ongoing by MSF in Swaziland that is looking at this I can't tell you the exact numbers all I can say is that their interim results are showing showing similar or slightly better results and the analysis by WHO did tease out a bit on HIV and it shows it seems to be performing the same in HIV you see I know this study is very important and there are several hands but at the same time Holly is showing me some paper you know what it shows so I'm sorry I'll have to wrap it up here thank you so much Philips thank you