Monday, November 30, 2015

HIV-related wasting can have long-term consequences

HIV-related wasting can have long-term consequences

People who suffered wasting in the past more vulnerable to frailty in later life

Michael Carter

Published: 30 November 2015

HIV-associated wasting can have a long-term impact on physical function and quality of life, according to research from the United States published in the online edition of AIDS. The research was conducted by investigators from the Multicenter AIDS Cohort Study. HIV-positive men with a wasting diagnosis were assessed an average of four years after their wasting diagnosis and compared with HIV-positive and HIV-negative men without wasting.

“The degree of impairment observed among HIV/wasting men may have significant clinical implications,” comment the authors. “HIV-wasting had a similar effect of 10 – 20 years of aging on self-reported physical QoL [quality of life].”

HIV-wasting syndrome was recognised early in the epidemic. Diagnostic criteria are involuntary weight loss of over 10%, either chronic diarrhoea or weakness and fever for over one month. Chronic weight loss and wasting are still among the commonest manifestations of advanced HIV disease. Although the incidence of wasting has declined marked with the introduction of effective antiretroviral therapy, initial weight loss may not be restored even with effective HIV therapy.
Because the long-term consequences of HIV-associated wasting are still unclear, investigators from MACS designed a longitudinal study comparing the physical function and physical and mental quality of life of HIV-positive wasting survivors with HIV-positive and HIV-negative men without wasting.

The impact of wasting on overall survival was also monitored.

Patients with wasting were assessed at least two years after they were diagnosed with the syndrome or other manifestations of severe weight loss (BMI below 18.5kg/m2, sustained 10% loss in body weight, or a 1%/kg loss of body weight each year during follow-up). Men with wasting were matched with men of a similar age who were recruited to the cohort at approximately the same time. CD4 count and viral load were used for matching with HIV-positive men.

Assessments of physical function included grip strength and walking speed. Physical and mental quality of life were assessed using accredited self-administered questionnaires.

Median survival was significantly lower among MACS patients with HIV-related wasting (9.1 years) compared to HIV-positive men without wasting (11.6 years).

“We found that the occurrence of HIV-wasting by any of our tested definitions was associated with markedly shorter survival than observed among HIV-infected men without wasting or uninfected men,” comment the investigators.

The study population for the assessment of the impact of wasting on physical function and quality of life comprised 85 men with a wasting diagnosis, 249 men with HIV and no wasting and 338 HIV-negative men.

Most of the study visits (80%) took place after 1996 – the year in which effective HIV therapy became widely available.

Men with wasting were assessed a median of four years after they were diagnosed with the syndrome. During this time, they experienced a small but significant increase in total body weight. However, they still weighed between 8-9kg less than men without wasting.

“We suspect that wasting in our cohort was associated largely with losses in lean mass, with subsequent regain largely representing fat mass,” comment the investigators. “The persistent low body weight and mean gain of only 2kg over 4 years is of particular concern in regards to long-term consequences in our cohort.”

At the time of assessment, the men with wasting had more co-morbid health conditions (2 vs.1), greater levels of use of stavudine (d4T) – an antiretroviral associated with fat loss (69% vs. 54%; cumulative use 2 years vs .05 years), and greater levels of use of therapy to counter wasting (testosterone – 38% vs. 22%).  

Men with HIV-associated wasting had lower grip strength and poorer physical quality of life than HIV-positive men without wasting (p < 0.03), and poorer physical quality of life but higher mental quality of life compared to HIV-negative men (p < 0.05). Walking speed did not differ significantly between the wasting and non-wasting patients.

When comparison was limited to patients with HIV, the association between wasting and physical quality of life ceased to be significant when lowest ever CD4 count and an AIDS diagnosis were taken into account. The association between wasting and grip strength was of borderline significance (p = 0.055), a likely reflection of the small sample size.

“HIV-wasting has a negative impact on muscle strength and physical QoL, years after stabilization of body weight,” conclude the investigators. “Prior studies have demonstrated that low body weight and/or poor strength are associated with low bone density, injurious falls, fractures, frailty, and ultimately, could result in a loss of independent living.”


Erlandson EM et al. Long-term impact of HIV wasting on physical function in the Multicenter AIDS Cohort Study. AIDS, online edition. DOI: 10.1097/QAD.0000000000000932 (2015).

Wednesday, October 28, 2015

HPV and HIV: What You Need to Know About Anal Cancer (Video)

Men who have anal sex with men (MSM) are more likely to get anal HPVthan men who only have sex with women. Researchers estimate that the prevalence of anal HPV among men who only have sex with women is around 15% while anal HPV prevalence for MSM is around 60%. If you add HIV into the mix, infection risk goes up still—one study published by HIV Medicine found that 77% of MSM with HIV were also infected with anal HPV; another study published by the Journal of Infectious Diseases found that over 90% of MSM with HIV were infected with at least one strain of HPV.
This increased risk extends to the strains of HPV known to cause cancer, with about a third of MSM living with HIV shown to have HPV type 16. MSM with HIV are also more likely to go on to develop anal cancer, with incidence rates per person-years as high as five times that of HIV-negative MSM. According to the CDC, men who have sex with men are about 17 times more likely to develop anal cancer than men who only have sex with women.

In this video, Dr Joel Palefsky explains what we can do to diagnose, prevent and treat anal cancer. He is doing the largest study in LGBT health history following 5,000 men for 5 years to asses the efficacy of anal dysplasia treatment versus monitoring.

Saturday, September 12, 2015

Best Posts on Aging with HIV from This Week


Thursday, September 10, 2015

Two New HIV Studies Give Access to Research Medications to People with Multi-Drug Resistance

By Nelson Vergel.

No one can deny that many patients can now suppress their HIV with effective antiretrovirals (ARVs) that cause fewer side effects. However, a vulnerable and often forgotten minority of people are still struggling with multi-drug resistant HIV (MDR-HIV) while they anxiously wait for access to lifesaving ARVs that would finally control their viral replication. Although some of these patients may have developed resistant HIV due to lack of adherence or other issues, many of them have been strictly following their doctors' orders for years.
They're often veterans of drug development research who have accumulated HIV resistance as they repeatedly joined ARV studies or traditional expanded access programs of a single new drug out of desperation to control their HIV viral load. As they signed up for studies that helped companies get their drugs approved by the FDA (U.S. Food and Drug Administration), many of these patients were exposed to suboptimal HIV regimens (namely, functional monotherapy or the addition of a single new active ARV to a failing HIV regimen). 
Currently, the U.S. Department of Health and Human Services (DHHS) adult HIV treatment guidelines recommend three antiretrovirals ( ARVs) be given in combination to suppress HIV. But many patients have HIV that has mutated rendering their virus multi-drug resistant (MDR-HIV). Those with MDR-HIV cannot construct a viable HIV suppressive regimen with current FDA-approved and commercially available ARVs. 
Fortunately, two companies are currently enrolling their phase 3 trials for two new drugs that provide a complete new mode of action in controlling HIV:  an attachment inhibitor (BMS-663068 from Brystol Meyers Squibb) and ibalizumab (a monoclonal antibody from Taimed Bilogics). With the encouragement from the HIV activist community, these two companies are providing access to their respective drugs for use in each one of their studies in combination to control the virus of people who have ran out of treatment options.
BMS-663068 is an oral prodrug of the molecule BMS-626529 and first-in-class HIV-1 attachment inhibitor. The attachment inhibitor is designed to work differently than entry inhibitors, a current class of drugs that targets co-receptors’ activity or fusion after HIV attaches to the CD4+ host cell. BMS-663068 is thought to work at an earlier point in the replication process to prevent the virus’ initial interaction with immune cells entirely, and thus blocks its entry into the cell.
Ibalizumab has a completely new mode of action, so most patients should respond to it when using it with at least one other active agent. It is different from the entry inhibitor maraviroc (Selzentry, Celsentri) in that it blocks the CD4 receptor on T cells rather than blocking the CCR5 co-receptor. This means it could be effective against virus that uses either the CCR5 or CXCR4 co-receptor. It is a genetically engineered monoclonal antibody administered once every two weeks intravenously. 
The studies currently enrolling share many of the same research centers across the country, so doctors can refer their MDR-HIV patients to these centers for access to both drugs at the same time. Please click on each one of these links to get more details about these studies:

Patients interested in joining these studies should talk to their physicians to have them contact the primary study coordinators listed in the two links provided.
Please feel free to contact me via email at for any more information on drug access for patients with MDR-HIV.

Webcast : Beyond the Berlin Patient- How Researchers Are Now Trying to Cure More HIV+ People

Webcast : Beyond the Berlin Patient- How Researchers Are Now Trying to Cure More HIV+ People

By Nelson Vergel

We all read headlines almost weekly about the latest HIV cure.   After years of being exposed to these inflamed news reports, we may get desensitized to the fact that there is actually progress being made in that field.  Ever since Timothy Brown was proven to be cured, the search for a cure for HIV has intensified.  There is more funding now as different research groups compete to get there first.  But we have had set backs that have taught us important lessons.  

I decided to interview two leading HIV Cure research advocates on a google hangout (webcast) to pick their brains about what has happened to people who have entered HIV cure studies. In particular, I wanted to get an update on the outcome with people who have been exposed to stem cell transfers, stem cell/CD4 cell manipulation, and those who seemed to control the virus after stopping antiretrovirals.  I hope you will find this webcast as enlightening as I did!.

Here are the video and transcript of the webcast entitled  Beyond the Berlin Patient- How Researchers Are Now Trying to Cure More HIV+ People


Scott Sillari:                        Hi guys. Scott Sillari here of Vyral Marketing. Welcome back to the Power Hangout with Nelson. Nelson, take it away. You're the man here. I want you to lead this and introduce us to our guest and what we're going to be learning today.
Nelson Vergel:                  Yeah. Thanks Scott. This is Nelson Vergel - hi guys - director of This is a series of Google Hangouts that we're doing once a month or so on different topics related to HIV health.
                                             Today, we have probably the hottest and most important topic of all, the actual cure of HIV. There are 33 million of us out there. Obviously, we have to take medications every day to keep the virus suppressed, and the cure, even though people say there is not such a thing, I mean there are conspiracy theories, we know that many researchers right now are trying to find a cure that is accessible to everybody in the world.
                                             We already know there is a cured patient. They call them the Berlin patient. We're going to talk about him, he's actually a friend of the three of us here in the panel, and we're going to get into details of what's happened after Timothy Brown was cured. Have researchers done anything to try to duplicate what happened to him and hopefully cure all of us. It will be a very interesting talk. It will be around an hour to an hour and 15 minutes. We will be transcribing it and you can watch it after the Google Hangout is over on
                                             I'm going to start by introducing our amazing speakers. I met these two men through my work as an activist. I'm part of the AIDS Treatment Activists Coalition. It's a coalition of activists that meet with academia and government and research and pharmaceutical companies to review and set the agenda from the community point of view when it comes to research in HIV. Richard Jefferys and Robert Reinhard have stood up through all the discussions and cure. These two men are committed. They love the science. They go to all the conferences. They read papers.
                                             Richard has a blog where he basically writes every month about what's happening with the cure. I'm very honored to have my two peer advocates and activists on this Google Hangout. Richard Jefferys has been with the Treatment Action Group, TAG, for the past 14 years where he now directs the Michael Palm Basic Science, Vaccines and Cure Project. The project covers the pathogenesis and immunology of HIV infection and advocates toward the development of immune-based therapies, effective vaccines and a cure.
                                             Robert Reinhard serves as a community liaison and steering committee of the CanCURE Research Consortium in Canada. He is also a research associate and community team member in the Dr. Mario Ostrowski lab at the University of Toronto where they're researching right now HIV cure or vaccine. Robert is a member of the IAS, Towards an HIV Cure, Industry Collaboration​ Working Group also. As you can tell, these two men have a great experience in following HIV cure research.
                                             I'll be asking questions. I'll be starting by asking them especially starting with Richard to tell us ... I mean most people who are watching this Google Hangout have never even heard about the fact that there is actually a person that was cured with HIV. Richard, start by describing what happened to him or even before him if we know of any other case and then we'll go from there.
Richard Jefferys:               Sure thing, Nelson. Thanks for the invitation to participate today, and hello to everybody. I think there’s been a little bit of confusion because there was actually this two Berlin patients. One was reported back in 1998. I think it was an individual who was treated very early after they had acquired HIV infection with antiretroviral therapies and then interrupted treatment a couple of times before permanently stopping. He was able to control his viral load to less than 50 copies for many years, and so there was a lot of interest in that individual. He was probably actually the first example of what you now read about sometimes as called a post-treatment controller. He had certain immune response genes that enabled him to be able to control the virus for a long time without the need for ongoing antiretroviral therapy.
                                             Probably the more famous now Berlin patient is the more recent case, Timothy Ray Brown, who underwent a really very challenging series of treatments that he needed for cancer for acute myelogenous leukemia which is a serious cancer. He required stem cell transplants, which is when you receive stem cells from a donor your own immune system is wiped out by a lot of pretty toxic immune suppressants, and after the transplant you get a new immune system that grows from those new stem cells. What his transplant clinician, Gero Hütter, in Berlin did was find him a donor that had this mutation that prevents HIV from being able to gain entry into the immune cells, and so when his immune system came back from the stem cells, it was resistant to HIV. He's now been off therapy I think for just about eight years, and the virus has never come back. He's been off antiretroviral therapy all that time.
                                             The original Berlin patient, there was an update on him recently. He still clearly has virus in his system and seems to be controlling it with his immune response to some degree. Timothy Brown is different because all active virus is gone. There's maybe a couple of trace, bits of genetic material they can detect but otherwise, he seems to be completely cured.
Nelson Vergel:                  Yeah. He's HIV negative, right, Richard?
Richard Jefferys:               The antibody responses are slowly declining. Yes.
Nelson Vergel:                  What is this about Berlin? Why do we have two people in Berlin? I hear Timothy is American, right? Why Berlin? What's so special about that city anyways?
Richard Jefferys:               I think one thing that's really key to this case actually is that is not specific to Berlin. It's just that the European healthcare system enabled the transplant doctor to go search for many, many different stem cell donors to find one that had this unusual and quite rare genetic mutation that prevents HIV from being able to gain entry to the cells. It's actually a receptacle CCR5 that's on most of our cells but a few people have a mutation which means they don't have CCR5. HIV uses it as a latch to get into CD4 cells that he was able to search. I can't remember the exact number. It may have been 60. I don't know if you remember, Robert. Sixty different potential donors till they eventually found one.
Robert Reinhard:              It's 255 or so. They only got one and that was even lucky, too. The odds were extremely low to find a proper donor.
Richard Jefferys:               In the US, the insurance would never pay for that. They'll never pay to screen that many donors.
Robert Reinhard:              That's right.
Nelson Vergel:                  Yeah. You were saying, and I think we can connect the whole case before we jump into other patients that have received stem cell transplants and more fancy things like that. The post-treatment controllers. Actually, as people may know, there are some people that can never get infected with HIV. Like one percent of the Northern European population has a genetic mutation that makes them basically they can't get HIV. It's very small. It's one percent, but there are some other people and it's very hard to predict, that they get infected with HIV, they get their diagnosis and they start treatment and then when they start treatment for many reasons, either side effects or something else, the virus does not come back up.
                                             As we know, we need medications to keep the virus from replicating so we call them - I don't know. We keep changing terms. Richard and Robert, you correct me up. I haven't been to a meeting in a while - post-treatment controllers. Tell us a little bit about ... Robert, too, if you want to add, maybe we can start with Robert on this thing about the VISCONTI Cohort and these guys or girls because I think there are females, too, that were able to have undetectable viral load for a while after stopping treatment.
Robert Reinhard:              I will throughout this talk ask, just as a general thing, for Richard to correct me if I'm wrong because I think he's pretty sharp, but  generally, the notion of a post-treatment controller is much different than the immunological circumstance and the experience of Timothy Brown.
                                             As I think Richard mentioned, during the course of your natural infection, certain cells are responsive to antiretroviral therapy. This is why people are able go to their doctors on a regular basis and determine that they are what we call undetectable, a word that really just shows that we can't detect the virus using clinically available assays, but really the virus is still hiding in reservoirs of the body where antiretroviral therapy cannot penetrate enough to attack the virus where it's sleeping and hiding. That is the main barrier to an ultimate cure.
                                             But it turns out that even under circumstances of what we think of as normal antiretroviral therapy that globally a few select patients have been identified in different circumstances, sometimes by accident, sometimes by design, they've been discovered where they've gone off antiretroviral therapy either voluntarily or in the course of some kind of monitored specifically-designed trial or observational study. A few have been discovered to be able to control the virus either to what we still think of as very low levels and without antiretroviral therapy or to experience different periods of remission or control of virus but then are later found to have to need to go back to antiretroviral therapy.
                                             I think what Nelson you were calling before the VISCONTI cohort, they've become the most famous examples of those. The VISCONTI cohort is a group of people - depending on how you count, how many there are based on the way that investigators have followed this group, sometimes they may go as low as 10 or maybe up to 20, but it's around that number - are group of patients who received antiretroviral therapy. People think very, very soon after they first became infected. In other words, the opportunity for the virus to establish and make a foothold in the body, in the immune system, they think was quite limited.
                                             Not only was the size of the reservoir likely very small or less than what people might experience during chronic infection but the potency or the ability of their own immune system to be preserved at that point without deterioration probably contributes to their ability to fight the virus if they go off antiretroviral therapy.  They may also have individual natural control.
Nelson Vergel:                  How long have we actually followed these patients?
Robert Reinhard:              They've been followed for seven years and some of them seemed to be able to control virus going out longer than seven or eight years.
Nelson Vergel:                  But they're not cured, right? They still have viral replication.
Robert Reinhard:              No. They're not cured absolutely in the Timothy Brown sense. There is certainly virus still on their bodies, but they seem to be able to control it at a level that people seemed to think of as clinically desirable endpoints even when you are on therapy.
Nelson Vergel:                  Do we know anything about these people? What makes them so special?
Robert Reinhard:              Well, there is the mystery. I think Richard probably has a lot better clues about that, but I alluded to a couple of possible answers of why that's true. One is it's possible that the size of their reservoir had already been controlled because they started early. Although that answer does not work for the vast number of other people that we also see who may have been treated early. There's something different about this cohort. The size of ...
Nelson Vergel:                  When we say early ... I'm sorry to interrupt. When we say early, how early is early?
Robert Reinhard:              They were given antiretroviral therapy at least within 10 weeks people think that they're becoming infected.
Robert Reinhard:              That probably contributes to their ability to control virus. Like I said, when you do control the virus at that early point, your own immune system which was always fighting the virus when anybody ever gets infected was not deteriorated as much as people who have late diagnosis and reduced CD4 count. In other words, when you do become infected, you do start to engage in a battle with the virus and you're partially successful, but eventually you lose that battle so their immune system has been preserved.
Nelson Vergel:                  Richard do you want to add something else before we move on to another cohort? We have an hour and we're going to cover all humans that have been tried in cure research because this is really about what we have tried already in humans not in monkeys, not in rats but in humans and what has not worked and not worked. Richard, anything else on the VISCONTI? Why do we call them VISCONTI anyways, VISCONTI Cohort?
Richard Jefferys:               It's an acronym for something that I've now forgotten.
Nelson Vergel:                  Okay. I thought it was a city in France!. It is a study acronym.
Richard Jefferys:               Yeah. Virologic immunologic control or something rather or I think it is. I think Robert covered it. I mean there is one not so good bit of news about that particular cohort that just emerged recently and a bit accidentally really. It was kind of buried at the end of a slide presentation from the recent International AIDS Society Conference which is that a couple of people in that cohort have quite significantly lost control of their viral load ...
Nelson Vergel:                  That's too bad.
Richard Jefferys:               ... emphasizing that it's not necessarily a permanent state including one person I think has a viral load of over 100,000 copies and another developed head and neck cancer.
Nelson Vergel:                  There's a new thing going on.
Richard Jefferys:               Yeah. There's possibly a reason to be a little bit concerned that in some cases the immune activity that's involved in controlling the virus may have some negative health consequences, but that's a difficult thing to know for sure because there's so few people in that situation but it's an important thing I think for future studies to look out.
Nelson Vergel:                  How about this term "elite controllers"? They're not the same as the post-treatment controllers, right?
Richard Jefferys:               They're different and that they've typically never been on antiretroviral therapy and they're just people that seem to have ... There's a very strong association with having particular genetics of your immune system and having really strong immune responses that target HIV. Again, there are some people, even though they control the virus very well and they're described as elite controllers, they can still very, very slowly over time, over decades lose CD4 T cells and experience progression. Again, it's not a perfect model although there's may be a subset of a elite controllers who control the virus extremely well who may be a better model for something that looks more like a cure.
Nelson Vergel:                  Good. I want to do a warning before we move on because many people who are watching this Google Hangout have never really heard about this topic. I want to make sure people understand the guidelines right now for treating people with HIV are basically recommending that you get treatment as soon as you find out you have HIV no matter what your CD4 T cells, your immune system is. That has changed.
                                             I think some people that I've talked to have this fantasy that they may be elite controllers so that their immune system will fight it off and they delay treatment. I want to warn that this cohort, this whole cohort is very small, less than 3% I think of the population of HIV positive. Don't ever take that chance to assume that you're an elite controller and have this fantasy because it is a fantasy. Seek treatment right away. As soon as you seek treatment, your viral load goes down, your CD4s go up, in most cases obviously, and you stop being infectious to others when your viral load is undetectable. That's something very important to know.
                                             As these gentlemen are telling us, and they will tell some more, it may in the future - who knows? - make a difference if you start treatment very early compared to later on when the cure eventually comes up. I believe we have no idea. I mean we're not talking about timeline but it's definitely not going to be even in the coming 10 years. There's a lot of work to be done. I just want to make this clarification because I don't want this message to be taken in a different way that can create some fantasies for some patients. Anyways, I'm sorry Robert. I interrupted before you started talking.
Scott Sillari:                        Real quick. Before we continue, I just want to mention, everyone that's watching in the upper right corner, there's some boxes. If you click in there, there is a question and answer application. You can ask questions throughout and we'll try to get to them or we'll get to them at the end. Real quick. Before you move on, Nelson, I got a question just about something that Richard said earlier with this Berlin patient, Timothy. If the doctors understood what type of cells they needed to replace these and there are certain people that they're able to get them from. I don't understand. I guess I'm ignorant to medicine in general but why can't they replicate that type of cell to use that for some sort of cure?
Nelson Vergel:                  Yeah. We're going to talk about this now. That's a good lead-in to the work that Dr. Hütter, the German doctor, has been doing to replicate and also work that some American doctors have been trying to do also with humans here to try to replicate in some manner that. I think Robert or Richard can take over on either Hütter's - I hate to mispronounce his name but that's a Spanish accent - has done after Timothy Brown to see if he can do it again in other patients, and then maybe we can move on to the work done in the United States especially in Boston. Either one of you.
Robert Reinhard:              One comment maybe I'd like to make going back to Timothy Brown as an individual person, we cannot say enough about what a sort of hero and model he really represents for activating the field of research about cure and as an example, both medically and personally in the way he has talked about it since then. The starting point for Timothy Brown's story as Richard mentioned is that he only underwent this procedure because he had already a life-threatening cancer. People don't go through that procedure unless they do.
Nelson Vergel:                  They would have to fail two rounds of chemo.
Robert Reinhard:              The great question that Timothy Brown's case brought up for the field of cure research is: Can we duplicate the result and can we move forward to get the benefit in people who don't have cancer based on the circumstances that probably led to his cure? So, not only the replacement of cells that might have this CCR5 mutation which are probably a very large part of the reason he was cured but probably not the only reason he was cured, but can we employ new techniques of chemotherapy in the circumstance of people who don't have cancer to give them the advantage that we think was the reason for Timothy Brown's cure.
                                             On that score, yes, there are companies right now and clinical trials in the works and also a big research collaboratory effort to try to engineer T cells either from your own body or using your own hematopoietic stem cells or generating these cells from your own CD4 reservoir and take them out of your body and engineer them with this CCR5 mutation and then reinstall them back into your body to confer this protection. Again, the example of Timothy Brown under life-threatening circumstances is giving a research program in the context of people who don't have cancer and probably could benefit from that approach. Richard, you probably have some good points to head, but maybe that's a little bit of the context.
Richard Jefferys:               I think that's really important context. Somebody that you could maybe have on a future hangout, Nelson, who you know very well is Matt Sharp, an activist who's actually participating in one of those gene therapy trials where they're modifying T cells to knockout the CCR5. He would have a lot of interesting information on that. I think there's been some published reports about those trials and little bits of potentially encouraging data that perhaps some of those individuals are able to control their viral load a little better.
                                             I'd also echo what Robert said about Timothy Brown. If you read any of the research papers that have been published about Timothy and look through the procedures that he underwent, it's really incredible just how altruistic he's been. I think he's had tissue taken from every part of his body to donate to science to try and help the research effort so it's really incredible.
                                             I think maybe one other thing that's worth mentioning is just that Robert talks about how it's being translated for people without cancers. There are also efforts and some studies available for people with HIV who do have cancers that require stem cell transplants that they will try and look for donors with this mutation to see if they can duplicate what happened to Timothy and other people. There's research programs in the US for both adults and children and adolescents with HIV and cancer needing stem cell transplants. There's a Europe-wide one as well and so there is a way of where people that needs stem cell transplants can see if they can get a CCR negative transplant.
                                             The bad news is that in the six people that have tried so far, and this emphasizes just how complex and risky the procedure is, unfortunately, all of them didn't survive either because of the cancer being so serious or because of what they called graft versus host disease where their body is going to reject the transplant.
Nelson Vergel:                  Yeah. Timothy Brown almost died three times, too. Richard, where can people find out about these studies or how to enroll? I mean who knows? Somebody listening to this may be going through cancer and HIV or lymphoma and HIV. Where do people find out besides maybe
Richard Jefferys:               Sure. is the central repository and then to shamelessly plug the Treatment Action Group website :
Nelson Vergel:                  You should. It’s great.
Richard Jefferys:               ... we do have a listing there that basically just compiles what's available or at least as much as we can find of what's available on the
Nelson Vergel:                  Thank you. Robert, do you want to add anything?
Robert Reinhard:              I guess I just want to add another little note about these ideas and these strategies. It does sound exciting not only about the innovation and the possibility of this kind of scientific research to imagine the possibilities, but when we start talking about these really major disruptions and replacement of your immune system and marshaling these different technologies to do it, we should be careful not to just say, "Oh, well, at least I don't have cancer so maybe I should try this." It sounds emotionally appealing but every procedure and especially these new immune-based procedures have risks of their own.
                                             As we were alluding to before, we think we have a good idea of why Timothy Brown was cured but we don't know absolutely exactly. A lot of the studies that Richard has mentioned, we are really trying to be sensitive to those important distinctions and it's important to think of these early trials as really again very early stage explorations to try to find not only the answers but also the right questions.
Nelson Vergel:                  Yeah. Let me ask you guys a question, a basic one because I get it all the time. We're talking about stem cell manipulations, transfers. As I said, this audience may never read about HIV. What happened to the vaccine? This is a virus. Why have we been so unsuccessful after millions of dollars in finding a vaccine for HIV? I know it's a very generic question but probably most people watching this would have it. You, Robert or Richard, you can both add because it is an answer that requires some explanation.
Robert Reinhard:              First, I would say that we haven't been entirely unsuccessful. I think people know probably from following the news that it's been a long time but after 30 years, the first clue for successful preventive vaccine was found in a large trial in Thailand which goes under the name of RV 144 where a limited amount of protection from HIV infection was discovered. Following up on that vaccine trial, there have been a number of attempts to find out why that trial have some limited amount of protection, how can we make it larger, how can we extend it to other people. That's one thing to point out.
                                             A big reason of why it's so difficult to find the vaccine is because the virus is found in many different forms throughout the world and figuring out the traditional kinds of blocks like whether antibodies are the reason or other kinds of immune responses are able to block HIV have been very difficult. Having said that, another benefit of the vaccine trials and the Thailand trial is that people in cure research are starting to think that maybe some of the reasons that vaccines worked, antibody or other responses might be available for cure research as well. Those are short answers to a really hard topic that again Richard is a great expert on but I just wanted to convey the context.
Nelson Vergel:                  Yeah. Thank you. Richard, do you want to take a swing at the very general question?
Richard Jefferys:               Sure. I totally agree with Robert. I think there is some really distinct signs of progress over the last decades and I think also that the burgeoning field of cure research has helped to rekindle some interest in using vaccines therapeutically. There's ongoing trials now where they're attempting to induce immune responses in the hope that they might help clear the reservoir of HIV that persists despite antiretroviral therapy. It's very early days and not really any signs of success yet but that work is ongoing and there's some hope there.
                                             Also, as they've got to understand antibody responses to the virus better, it's become clear that they can perhaps help target the cells containing HIV for elimination so there's a lot of interest in using what they call Broadly Neutralizing Antibodies in cure research. There's a bunch of trials already ongoing of several different of those antibodies and the interest in combining them, in fact plans to combine them with agents that might wake up the reservoir in people that are on antiretroviral therapy. So, although there's been a lot of money spent, it is paying off and I think it's not just going to pay off in the prevention realm. It's also paying off in the therapeutic research.
Nelson Vergel:                  Richard, I was talking to you before like today, and this is a very generic question, too. We're trying to not only make this a science-related hangout but one that discusses all the things that I get asked all the time like there are many people out there that think that the cure is already available and that pharmaceutical companies are basically not wanting to cure HIV because they want us to take the medications for the rest of our lives. They really don't know, that's why we're doing this Google Hangout, that there is a lot of research going on. What do you tell people when they say there is actually cure and pharmaceutical sector is basically hiding it from the world?
Richard Jefferys:               When you look at the certain things in history, you can understand where people can be very suspicious of what's going on particularly of mainstream government institutions and so on. I think though the reality is if you look at the example of hepatitis C particularly recently, there's been a lot of development of therapies that are curative essentially of hepatitis C that are effective and are getting safer. The only thing that there is a definite profit motive there and the bad side is that companies, they have no problem making these curative therapies, they just want to charge a really large sum of money for them.
Nelson Vergel:                  A thousand dollars a day like for hepatitis C.
Richard Jefferys:               Yeah. I think it's not that they don't want to. If they could develop a cure for HIV, if there was one already, it would be out there. It would just cost a lot of money probably and activists will be having to do the work they did with antiretroviral therapy to try and make sure that the price came down.
Nelson Vergel:                  All right. Let's switch to another topic of not cure but remission. In the media, maybe over a year, two years ago, we were hearing about the baby that got that cured in Mississippi. Everyone was talking about the baby that got that cured with HIV. Can you guys bring us up to speed on what happened to the baby and if any other babies have gone through the same experience after that baby. Mississippi baby, they call it. Right?
Richard Jefferys:               I think Robert follows pediatric research very closely so he might be able to answer that.
Robert Reinhard:              Okay. Just to clarify. The Mississippi baby was an example of what I mentioned earlier. It wasn't a pre-planned investigation. It was accidental, a finding that a family which was in very difficult circumstances presented to a clinic where the mother had not received the kind of prenatal care and care during pregnancy that we would like to see every mother have. The child was found to be infected at birth but luckily for that child, the medical team that was investigating thought, "Well, we were able to determine this right away. We're going to put this child right away on a complete regimen of antiretroviral therapy and see if that is helpful for this child."
                                             The family continued to provide antiretroviral therapy to the baby but again because of personal circumstances in the family, the child actually went off antiretroviral therapy and when the family was able to reenter the clinic setting, recognizing that antiretroviral therapy have not been given, it was found that the child seemed to be undetectable. Not only undetectable in the clinical sense but we mean normally but they couldn't find virus no matter how hard they looked in this child.
                                             Now, that circumstance continued for a period of about 27 or 28 months. Then after 28 months, without much warning but maybe with a little bit of warning, the virus rebounded and resurfaced in that child. The child had to go back on antiretroviral therapy and fortunately that's been successful and the child remains healthy and controlling the virus. The Mississippi baby had first entered the news media as an example perhaps of the second person that might have been cured but it turns out they weren't.
                                             What's very interesting about that child, and we shouldn't necessarily call it a failure, the question is not why so much the virus rebounded or why it's important but why did it take so long? Why was this child able to control the virus for 28 months? Because normally when you go off antiretroviral therapy even as a child, the rebound time is very short. That has sparked a great effort to try to expand or to look at pediatric care and the possibility of remission strategies for children worldwide and in other countries.
                                             In a sense, infants and babies are almost the ideal subjects for testing the idea that if you give antiretroviral therapy right away upon diagnosis, you may be able to control the virus when they get off of therapy because we got them right there. We know when they were infected right away. It's not a matter of somebody going to get tested later on.
                                             In Canada, there has been an effort to try to find other examples of children that are given antiretroviral therapy immediately upon birth or within the hours of birth. Four children at the moment are being followed. They are still taking their medication but the assays that were used to find the virus in these children still cannot detect virus. So, it's hopeful that maybe they will be examples of this kind of post-treatment controller.
Nelson Vergel:                  We hardly have any babies that get infected anymore, right? I mean you want to make that distinction to the audience that at least in the developed world ...
Robert Reinhard:              That's right.  But in LMIC countries it’s still very serious, 220,000 children in 2014. We always have recognized that any child that is born today with HIV infection is to a very large degree a failure of the healthcare system because we're quite able with good prenatal care, with attention especially during the period just before delivery, at delivery and post-delivery to make sure that every baby born to an HIV-infected mother is virus free. A great effort in global response is to make sure that we expand on that possibility. Nonetheless, despite best efforts, children will be infected. We're not there yet.
Nelson Vergel:                  That is usually when the mother is treated for their HIV and they're successfully treated, they cannot pass it on to their babies at birth. Right? That's what we know.
Robert Reinhard:              That's part of the way of preventing mother-to-child transmission along with other things, like also giving drugs to the child for a time. A big circumstance to be concerned about for families globally is that even if you're successful at preventing infection through the birth process, breastfeeding continues to be a period where it's possible to transmit virus.
Nelson Vergel:                  That's true. Guys, we were talking about controlling the virus after treatment. Do you want to discuss that graph that we brought up before? Right now I think is a good time to bring it up. Or do you guys want to add anything before we do so?
Richard Jefferys:               Sure. Now would be a good time. I just realized there's a couple of other cases that are sometimes have to be somewhat similar to the Mississippi baby which is these two adults in Boston who also a bit like Timothy Brown, they had a serious cancers that required them to undergo stem cell transplants but they received stem cells transplants from normal donors so they weren't HIV-resistant stem cells. They remained on antiretroviral therapy through these procedures and what happened is that after the transplant had successfully rebuilt their immune system and the cancer was in remission, when the doctors looked for their HIV reservoir, it couldn't be detected. I think they all mentioned on this slide there were two individuals ...
Nelson Vergel:                  Let's expand it if we can before we go on. Can you expand it a little, Scott? I think it's also hard to see the bottom because we are covering the Y axis.
Richard Jefferys:               Let me see. Yeah.
Nelson Vergel:                  Just put it up a little maybe or maybe decrease ... There you go. Maybe the other way around. Make it smaller I guess. I guess I want the smaller. Hey guys, just technical issues that we go through in a live show. Well, we'll leave it as is. I think that will do. Just small. Yeah. We'll leave at is. I think we can make it work.
Richard Jefferys:               I think that's fine.
Nelson Vergel:                  Yeah. Richard continue. I'm sorry.
Richard Jefferys:               What they did when they realized that they weren't able to find virus in these two individuals, they had to stop antiretroviral therapy, they did a lot of checking with their ethical review. People at the hospital in Boston where these patients were being seen and eventually got permission to interrupt the antiretroviral therapy, and similar to what happened to what happened in the Mississippi child, there was no evidence of rebound for some period, and some of the news, initial news stories were suggesting that there might be additional examples of cures of HIV infection.
                                             Unfortunately, again, there was a viral load rebound somewhat quicker in the child one at three months, one at eight months but I didn't have any immune responses against the virus and so it doesn't seem to have been the virus is controlled. The thinking right now is just that they had such a small reservoir that it didn't wake up for quite some time.
Nelson Vergel:                  Richard, before we ... I'm going to interrupt you here.
Richard Jefferys:               That's fine.
Nelson Vergel:                  For everybody that is watching. ART means antiretroviral therapy which is a combination of at least three drugs to treat HIV. The lines in the graph, we have two green lines; one orange, one purple, one red. Those are actual people, right? Or cohorts maybe. We can say that.
Richard Jefferys:               Sure.
Nelson Vergel:                  Not people but they are groups of people. Some are one person . The red one is the only one that is flat throughout and that's Timothy Brown?
Richard Jefferys:               Yeah.
Nelson Vergel:                  The purple one is the VISCONTI trial, the people we talked about that controlled their virus at a low level after stopping treatment and then the orange one that goes up later on, the viral load goes up is the Mississippi child right after 28 months. The green one on top of that is the Boston, I guess one of the Boston patients. Eight months? What did it say? The other Boston patient their viral load goes up after three months of stopping.
Richard Jefferys:               Yes. I think that beige one is what typically happens when somebody stops antiretroviral therapy where it comes back within a few weeks.
Nelson Vergel:                  What we want is everybody to be in a flat line on zero, right? Because when you're cured, you have zero viral particles. You may have like you said remnants of the virus like Timothy has but they're not real viruses, right?
Richard Jefferys:               That seems to be the case. I think the other important thing about the Boston patients and the Mississippi child is that during that period when they were off antiretroviral therapy, it wasn't just the viral load is undetectable. All these other very sensitive measures that they have of HIV DNA that they call the reservoir outgrows to see if they can find virus that can replicate. They couldn't find that anywhere. I think they even looked in different tissues of the Boston patients and they couldn't find it. It really seemed to be just no viral activity for that period and then unfortunately, it started up again.
Nelson Vergel:                  Would you say we're going through a rough period or are we ... I know Robert is very ... His language is very optimistic. He says we're not failures. We're learning. Obviously, we are learning through all these cases but at the same time, are we starting to lose hope or are we getting into an area where ... Everybody, I mean I get people emailing me at where I answer questions about the latest cure. Everybody watching this Google Hangout, if you've been on Facebook or on TV or radio whatever, we've heard about the latest researcher that found a cure. People are getting either numb to the word cure or they're getting cynical about the word cure. Is excitement starting to fade away after Timothy was cured? Anybody can answer that. Robert or Richard.
Robert Reinhard:              I think I'd like to go back to a little thing about what Richard was just saying that even with this very sensitive, very particular assays and sampling in the tissue where for the period of remission we couldn't find it and then it comes back, it just shows you really how difficult scientific question this area of study has become. Like any kind of very difficult and very important ... I mean you started out, Nelson, by reminding everybody that globally millions of people who have HIV are living under a lot of different circumstances. How can we turn these few example, I mean we're talking about people 10, 20, 30 people compared to millions of people who have HIV.
                                             What are the clues that we're learning from them? I think we are learning a lot of clues, but to me, when I read these newspapers accounts of another person, another cohort, what it reminds me of is not that these are necessarily going to be the examples of cure. It reminds me of how people should still be interested in research. The interesting participation of humans right now is not so much clinical trials although they are important. I'm more interested in people getting interested in the idea of allowing sampling or explorations of where the reservoir is,  not so much in the example of a clinical trial with an intervention, so that we can answer these questions. Why does it come back? Where is it hiding?
                                             There's a great need for people to be engaged in the questions of answering not only did they have cure remission but why? What can we learn by exploring samples in their body? That's an earlier stage and I think there is hope if we continue to look deeper.
Nelson Vergel:                  Richard?
Richard Jefferys:               It can be difficult because the media is not great about writing about science generally and it will always go for the headline type of story. I think when you read a lot about cure for HIV, it's a particularly potent thing because this has been heavily stigmatized infection and so there's a powerful desire, an understandable desire out there to get to a cure and reading about it for years, you do wonder actually what's going on.
                                             I think one encouraging thing is that it has quite quickly become such a major focus of the research effort. I think there are some quite incredible people that may have been instrumental in making that happen including Françoise Barré-Sinoussi who is one of the discoverers of the virus and so there's a real drive out there in the scientific community to get to the point where a cure is achieved. I think that is reason for some optimism but at the same time, you have to be wary of the headlines that make it sound that there's going to be some quick fix because science is challenging. It's complicated.
                                             They are incredible, and Robert knows much more than me about some of the very detailed practical issues that are involved in conducting research studies in companies agreeing with each other that they're going to combine different therapies that might be important to combine in these studies. There's a lot of stuff that has to be gone through. It's not just bureaucratic. It's about protecting people and making sure that in some crazy rush to test something, someone gets killed or injured which would be really terrible.
                                             I think that there has to be a certain amount of caution but at the same time, there are encouraging potential treatments and I think maybe the Broadly Neutralizing Antibodies that we've mentioned earlier as one example of something that does look very good which is being studied right now. There's going to be results from those studies within the next few years. There are some things at a nearer time that I think are worth looking forward to. I'm not saying they're going to be curative but I think there's the potential for taking some steps forward in the near time.
Nelson Vergel:                  You were mentioning about companies or researchers trying to collaborate but who's funding this cure? Do we have enough money to research the cure? A few years ago or maybe three years ago, I made a video that actually made the point that we didn't have funding.
Robert Reinhard:              As usual, if you look at the map of the source of the funding, the largest share comes from United States. Maybe I should let Richard take this over but there is an organization which is a collaborating effort between AVEC. TAG also contributes and a number of people to look every at the level of funding for now cure research but also for other research directions like vaccines and other prevention modalities. A big boost to that level of funding came in the last couple of years from the NIH which again under an almost presidentially-directed initiative by NIH strategy plan to elevate your research as a priority effort among the different funding tools or pots of money and each year, that line of money keeps going up. Is it enough? Well, it's hard for people like us I think to judge exactly how many dollars are not only being spent but are they being properly spent? Are they being well-spent?
                                             I think there is a general sense that sure we need more money but we're competing against a lot of other things that are also important. I think we have a great trend that government sponsorships, foundation sponsorships, and private company sponsorship is trending in the right direction. When we have more successes, when we can get more initial findings that give direction. That's when people start piling on more money where they see a chance of success.
Nelson Vergel:                  But there's at least much more funding that we had just three years ago and there's a lot more activity.
Robert Reinhard:              Absolutely.
Nelson Vergel:                  There are - what? - four or five conferences a year on cure stuff so it's very active. There is a competitive feeling in my point of view when I go to meetings about finding a cure. What I'm finding out too is that we're going to get people to ... We're going to have to make them work together because the cure may actually be a combination approach. It's not going to be one thing. It's going to be a combination of maybe antibodies and stem cells and treatment, and this flush agents that actually flush the virus out of them. That's it. That's probably the hardest thing. People study different modalities by themselves and I don't think we are yet in the combination phases of maybe a stem cell we combine it with treatment. Do you think that's a barrier? Probably one of the hardest barriers is to get people to combine their different approaches.
Robert Reinhard:              I think as a business matter, that's a very important consideration. I mean it's hard to get people to mix and match the combinations that are based purely on what makes the best biological sense when people also have a competing interest to think about. What is it that they can control in terms of their operations?  I don't want to say I'm too cynical but we know from the preventive vaccine field that it takes a lot of work to get combinations that make biological sense to match or harmonize with combinations that are owned by different practices.
Nelson Vergel:                  Yeah. Something else I want to add is that any research done in HIV cure research actually helps the world in all kinds of immune-based research for all different pathologies so we're learning things working with HIV and immune-based stuff that can be applied to other diseases. Also, we're learning from cancer as we know in some studies. Anyways, we're getting really close to ... Basically, it is the time to close the hangout.
                                             Richard, do you want to add anything? I want to find out two things. How do people get involved if they want to get involved? There are people like you, you guys are working your asses off trying to be the best activists that go to meetings and advocate to review the previous search and digest it for the patients to make sure that patients that are enrolling in studies know about the risk they're taking and know that this is an altruistic thing that we're doing. Most studies are not going to benefit or all studies right now are not going to benefit the patients. The patients enrolling in these studies are basically doing it to help the world.
                                             Richard and Robert and myself and others are not as I said as much involved as they are working hard and they need help. How do people get involved in HIV cure research activism? (b) How do they contact you? (c) Where can they learn the basics? One more thing to add. You guys work for nonprofits. Do you guys actually take donations from people? I have four and I'll remember them again if you guys forget. Let's start with how do people get involved. Richard.
Richard Jefferys:               I think there's a few different groups there. There is actually some talking about funding, the National Institutes of Health and the US Funds, the Martin Delaney Collaboratories. There's going to be some new ones funded. There's community advisory boards for those collaboratories. If you go to the websites, if you look up Martin Delaney Collaboratories, there's contacts there for people and you can ask about getting involved, and particularly look out next year when there will be an announcement from the National Institutes of Health about newly-funded collaboratories. They'll say where they're located and it will be possible to contact people if you're interested. I think also, the amfAR is supporting a lot of research. I think in terms of donations that money definitely goes to research projects. They've funded quite a lot of innovative research there.
Robert Reinhard:              I'd like to add a little to what Richard said and that is again, going back to where you started out Nelson. Really the distribution of the number of people who need cure, who deserve a cure is global and we really need to find more ways to have community engagement, education, involvement and participation where the epidemic is. On that score, there's certainly an awful lot or work left to be done and it's great that a lot of activity has happened so far in the United States, but really a challenge is to reach people globally First of all, I'd just like to say having more educational opportunities like the one you're providing is a great thing to always be doing.
Nelson Vergel:                  Thank you.
Robert Reinhard:              Really we need to think about engagement where a cure is desperately needed everywhere because everyone deserves it.
Nelson Vergel:                  I'm just going to plug the next hangout. Everybody thank you for taking the time. It's a little over an hour and it was a very dense material. We'll have a transcription of the material so you can actually read it. There are some words that may or may not have made any sense to you but we'll try our best in the transcription to describe them to you. Our goal as I said is to bring everybody up to speed in the fact that there are a lot that is being done to fund a cure for HIV, there's no conspiracy theory and remember to take your medications if you're HIV positive. The sooner, the better.

                                             We will have a Google Hangout every month. The next one I'm looking into two different topics on aging and HIV. We're going to probably talk about cognitive function. Anyways, stay tuned and you can also as I said watch this video on YouTube. Thank you so much and stay tuned, and find out from our emails and Facebook postings for the next one in 30 days or so.

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