 Good morning. Kaposi sarcoma, or KS, is one of the most common HIV-related malignancies. It's particularly prevalent in some parts of Southern Africa. It's linked to a herpes virus, and it's actually a cancer of the walls of blood vessels. It has a variety of clinical forms, as you can see on the screen. The lesions on the left on the palate are typical mucosal lesions. Similar lesions can also occur on internal mucosal surfaces, like in the airways or in the gastrointestinal tract. And when that happens, life-threatening bleeding can often occur. Otherwise, the external forms have a variety of different forms. You see the very thick plaques, different sorts of macules and nodules. And you can see on the right that when the extremities are involved, there's often a dense lymphedema, which causes great pain and great disability. The basis of treatment is antiretrovirals. And in the early stages of Kaposi's, ARVs alone can actually be enough to reverse or at least control the cancer. But once the chaos becomes advanced, systemic chemotherapy is needed. And regarding chemotherapy, there's a big divide. In sub-Saharan Africa, access to chemotherapy for any cancer is very limited. And even in places where chemotherapy is available, the standard of care for Kaposi's is a poorly tolerated three-drug combination associated with a variety of toxicities like myelosuppression and severe peripheral neuropathies. And regarding doxorubicin, at a certain cumulative dose, it's associated with the development of cardiomyopathy. But in rich countries, for many years, the standard of care has been pegalated doxorubicin, or PLD, like I'll call it for the rest of my talk. This formulation of doxorubicin provides a longer serum availability of the drug. So effective concentrations stay for a longer period of time, allowing the drug to be used in monotherapy, meaning fewer side effects and fewer total doses received. But it's very expensive and not widely available in developing countries. And since doses are dependent on body size, I can't give you specifics, but we're talking about several hundred dollars per round of treatment. So in Maputo, MSF offers specialty HIV and TB care, including treatment with second and third line HIV drugs and care for patients with MDR and XTR TB. We've also treated over 1,800 Kaposi's patients since 2010, which means that it's actually one of the largest Kaposi's cohorts in the world. And while the quality of care is high, I have to be honest that I think the outcomes are so-so. Only 40% of our patients receive complete or partial remission. And those who do need many cycles of this toxic triple therapy. And over 40% are either lost to follow-up or known to have died. So this is obviously an ideal setting to pilot the use of PLD in Sub-Saharan Africa. MSF was able to procure a supply for use in Mozambique, and we put in place an observational study to document its use, the first widespread use in Sub-Saharan Africa. And we hope that documenting this experience will lead to improvements in the price and availability of the drug, and eventually changes in national protocols. Chemotherapy naive patients were eligible to receive PLD. As part of standard procedures, women of childbearing age agreed to contraception prior to receiving any cytotoxic medication. PLD has given every three weeks until complete remission or until partial remission with significant improvement in pain and edema. Prior to infusion, same-day chemistries and blood counts are performed. If the hemoglobin is between 8 and 10 grams per deciliter, PLD is given, but we send the patient directly for transfusion afterwards. And if the hemoglobin is below 8, PLD is withheld, and we send the patient for transfusion. PLD is also withheld for an absolute neutrophil count below 1,000. And now, to a European oncologist, this setup would likely seem standard. But I'd just like to underscore the effort it's taken to have the laboratory capacity to provide these tests and results on the same day and the same morning within an hour, and also the close collaboration that we've developed with our friends at the blood bank at the central hospital in Maputo. In addition to chemotherapy visits, patients come for schedule study visits six times over the course of two years and benefit from routine psychosocial counseling and evaluations. A total of 168 patients were screened between March and December, 2016, of whom 130 were eligible for the study. Of those who were eligible, 116 were enrolled, and of the 14 that were eligible but didn't participate, eight specifically declined, and six agreed to participate, but then did not come for enrollment. So a majority of the patients were men and actually not that young. At the time of enrollment, they had varying degrees of immunocompromised, but about half had a CD4 under 200, and a quarter had a CD4 under 73. Half had been diagnosed with HIV for the first time in the previous six months, and current or past TB was also common. Follow-up is ongoing, but we have outcomes at six months for 91 of the 116 patients. Over half have had complete or partial remission, and only one quarter have had what I would consider a negative outcome, progressive disease, lost of follow-up or death. And as you saw in some of the pictures before, many of our patients have extensive Kaposi's disease, so complete remission will be very difficult, even when they have full immune reconstitution. So these six month results are very much in line with our hopes and expectations. This figure shows the number of cycles of chemotherapy received, and you'll note that the patients who died or were lost to follow-up generally did so very early on after entering the study. The median of six doses of PLD was needed among patients achieving complete or partial remission. And as a reminder, in our historical cohort, patients needed a median of 10 doses of the triple therapy to achieve complete or partial remission. But a picture is worth 1,000 words. So these are the same four photos that I showed you earlier, and I'll show you the lesions, the same lesions that six months of follow-up. So there you see the complete remission of the palo lesion, the plaque, which is greatly decreased, and the edema decreased. The macules almost disappeared, and finally, the nodules completely disappeared with great improvement in the edema. My favorite one is the following. This patient was enrolled with extremely painful lesion on her nose, massive, painful periorbital edema, and she could barely see. She received six doses of PLD between April and August 2016, and this is her in September 2016. She's continued to follow up and is doing quite well. So we've also been following the safety, and 11 deaths, frankly, seems like a large number. But given the severity of illness and advanced immunocompromise of many of the patients on enrollment, it's not surprising. Five have died of what I would say terminal HIV in the setting of social difficulties, like family problems, homelessness, drug use. And three others have had those same social problems with a confirmed opportunist infection on top of it. Among the others, one passed away with disseminated mac, another of a lymphoma, which had actually gotten better while she was receiving treatment for her caposes, and then the third was a patient with known cardiovascular disease who died of a probable stroke. Three non-fatal essays have been reported, one of which was directly related to PLD. And 43 adverse events have been reported. Most of which, hematologic in nature. So before concluding, I'd just like to remind you that this is an observational study not designed to make comparisons with our historical cohort and that our follow-up is ongoing. Nonetheless, we're extremely satisfied with the overall results that we've seen. And anecdotally, our participants are quite happy as well. And the safety profile is quite favorable, but the number of deaths brings up important questions about allocating resources, because it's unlikely that PLD will be able to be used in all patients moving forward because of the cost. So the question of who should be prioritized to receive PLD versus the traditional triple therapy, it's an open question. So we're going to continue until all patients have been followed up for two years. And in the near future, we'll begin analyzing the psychosocial data as well. So I believe that our results show really good reason to push for better access to PLD in sub-Saharan Africa. And already other MSF projects in Kenya have begun to roll out PLD, and discussions are ongoing for a project in Kinshasa. But obviously, lower prices and better access, better availability, will be necessary for scale-up, both for MSF and particularly for ministries of health. And I think it's a good time to point out the very good news we received earlier this week that a generic provider, generic producer, was approved by the US FDA earlier this week. So we hope that that will be a positive force on the market. Thank you very much for your attention. Thank you very much, very clear. So again, we have time for a few questions of clarification. Looking around in the room. Yes, right in front, Ban. Can you introduce yourself and which organization you belong to before you ask the question? OK. Thank you. It's Berne from MSF. I just wanted to get some clarification. I might have missed it. But when you're looking at the efficacy or the changes after using the new intervention, did you also look at whether there have been any changes in terms of the ART that has been provided in the patient? So the other one, just to say whether you consider it's great looking at the pictures and they really tell 1,000 words. But have you considered also having some qualitative evaluation in terms of the patients telling their story of how it improved? Thanks. I'd like to take if there's any other clarification question before my response. Right at the back of the room to the right, yes. Over there. And one question, please. Introduce yourself. I'm Helen Bygrave, one of the HIV TB advisors in MSF Belgium. Matthew, I just wanted to ask, I'm sorry if I missed it. Because in terms of allocation of resources, who should get it? Were any of these patients relapses on previous treatment or non-responders on previous treatment? Thinking about where we might be able to go with this. So I will add one clarification question to that, which is, so you said it was an observational design and not intended to make any comparison. Do you have any data on the program, the rest of the program, as to how well people did that you could compare if you have to? Sure. So if you can respond to those three questions. OK. Should have brought up patterns to take notes, so. I can remind you if you. To answer, Helen, to answer your question very briefly, they were chemotherapy naive. We wanted, at least in this first rollout, to do it on chemotherapy naive patients to give ourselves the best shot to show how it's working. I think that's a very valid point. And then regarding the historical data, we definitely have the historical data. I think there's questions about how outcomes were judged. I think maybe they were less standardized than when we're doing now this perspective study. But I think that the outcomes were quite poor. I think in the other large cohorts in Southern Africa, you look at 35% loss to follow-up or death. We have about similar in our historical cohort, 40%, 43% loss to follow-up or death. I think what you need to realize is that whatever we're doing, these are quite ill patients. And they're coming at an advanced stage. Regarding the questions about qualitative research, we haven't done specific qualitative research, but there are data that are being collected regarding psychosocial aspects. We're using the SF-12, which is a functionality score, as well as standardized psychological screenings. Those data just haven't been analyzed yet. Regarding antiretrovirals, we have history of ARVs for all patients. 95% of patients that you see here are on ifavirins-based triple therapy, the sort of ifavirins, emtracidabine, and tannothalium. A few are on protease inhibitors, but not that many. And we are following who gets what and who's changed what points. Thank you very much. You remembered all four questions. Thank you. And I only had one cup of coffee this morning. Thank you.