I am a physician and scientist working to find an HIV vaccine. AMA.
My name is Darpun Sachdev, and I’m a physician who does clinical research to try to find an HIV vaccine.
I’m trained in Internal Medicine/Infectious Disease and I provide primary care for HIV-infected patients. I’m also a study physician and HIV Vaccine Fellow with Bridge HIV at the San Francisco Department of Public Health, where I provide scientific expertise and leadership to conduct Phase I-III vaccine trials in the SF Bay Area. Bridge HIV is a leader in HIV prevention research, working to discover effective strategies that will reduce the impact of HIV/AIDS. Right now, we’re part of a large, nationwide, phase 2B clinical study evaluating the safety and effectiveness of an HIV vaccine (here’s a link to our study website: sfisready.org).
A couple of weeks ago, there was a post here talking about HIV vaccines, and I thought I’d make myself available to answer questions from a clinical scientist’s perspective. I’m looking forward to telling you all about my work.
EDIT: Here's proof of my identity!
EDIT: Okay folks, I am going to keep an eye on this AMA, but I'll get back to you tomorrow. Keep firing away!
EDIT 1/3/13: Thanks for all the great questions! It's been fun. For more information on HIV vaccine research, check out our website, sfisready.org, or the website of the HIV Vaccine Trials Network.
That's a really good question and it's one of the major challenges facing the field. Currently, several HIV vaccine candidates are trying to target highly conserved regions of the HIV envelope (outer structure of HIV). These highly conserved regions do not evolve rapidly like many other parts of HIV. We know that generally speaking in HIV infection broadly neutralizing antibodies often develop, but these antibodies typically do not neutralize virus. The goal at this time in the field is to stimulate broadly neutralizing antibodies that target highly conserved regions of HIV and neutralize the virus.
Recent HIV vaccine research has focused on "structure-based vaccine design" which uses the crystallographic structure of the HIV-envelope epitope to identify the precise binding site of a broadly neutralizing monoclonal antibody. This publication summarizes what we know about broadly neutralizing antibodies that bind to highly conserved regions of HIV. I do not have the PDB file.
Do you get a lot of questions about Zombies?
Was there any truth to the rumors that HIV was being used to cure Cancer?
How long have you been working on the vaccine?
Do you work with HIV patients a lot?
Could you detail how research into a vaccine actually progresses? Some of the details and processes?
- I hope not because I don't know too much about zombies.
- I read about that but it is not my area of specialization
- Bridge HIV has been working on HIV vaccine studies since the late 1990s.
- I see HIV-infected patients every week in my role as an Infectious Disease fellow.
- So it all starts with an idea in a lab. Scientists conduct experiments that suggest that a particular vaccine candidate may prevent infection or delay progression of HIV. This product is typically tested in non-human primate model. The vaccine candidate then progresses to small human studies testing for safety and then larger human studies testing for safety and efficacy. Eventually a very large randomized clinical trial must be performed to determine if the vaccine candidate works in a given population.
So, vaccines are meant to prevent diseases/viruses/what have you from infecting people. If you were to do a large-scale trial of the vaccine on people, would you have to infect them with HIV?
Or am I misunderstanding the shots I got as a kid?
We absolutely do not infect individuals with HIV in order to test vaccines. We typically conduct large scale trials to evaluate efficacy in specific populations where individuals are at higher risk of acquiring HIV. All of our volunteers receive state-of-the-art HIV prevention care, including regular risk-reduction counselling, free condoms and frequent HIV testing.
So, if I'm reading this right, even if you, say, discovered the vaccine today, trials and such would take several years before you'd be able to say with any concrete certainty that you had found it, yes?
This is facinating. (I am glad you do not infect people.)
Exactly. The process of testing a candidate vaccine takes years and it is important to be sure that the HIV vaccine candidate works against the diverse HIV subtypes (strains) found in different populations worldwide.
How far away are we from an HIV vaccine?
Clinical research takes a long time, so even if we found the vaccine tomorrow, it would take many years of testing to show that it's safe and effective.
There is no 'good' strain of HIV. A very small minority of indivduals who are HIV-infected are long-term nonprogressors, but many times even these people develop AIDS and require antiretrovirals. We think that long-term nonprogressors may have special genetic and immune responses that alter the normal progression of disease, as opposed to the virus having special properties.
I was watching a program think discovery don't really remember. They were talking about this lady in an african village that is immune from the disease. She was a prostitute and had been sleeping with men for years that were infected with aids and after many test she still had not contracted the disease. The doctors asked for her permission several times to take blood and analyze it to figure out what the difference between her and everyone else to try and make a vaccine. After several months of pleeding with her she finally consented and the doctors to blood and began to study it.
Are you familiar with this story? Is the medical field making any strides to success from testing her blood?
Thanks and Happy Holidays.
HIV exposed seronegative individuals (HESN) have been identified in many areas of the world, with a very well-defined cohort being a subset of female sex workers (FSW) from Nairobi, Kenya. Researchers are still working to identify if there are markers of protection that could be adapted to develop an effective vaccine. Not surprisingly, it appears that there is a combination of innate, genetic, and acquired immune-mediated mechanisms that provide protection in this subset of women.
I'd like to thank you for your research. Though I do not personally know somebody who has been affected with HIV, I have heard many stories about the tragedies that HIV can cause.
With the knowledge that we currently have about HIV, is it possible to estimate when an effective vaccine will be created?
How much money do you receive annually from the Government? From charities?
What made you decide to research HIV vaccination?
Where did you go to school?
We are not sure when an effective HIV vaccine will be ready. We think that we are probably several years away from a successful vaccine. We are currently conducting several safety studies with promising new HIV vaccine candidates.
As a care provider for HIV-infected patients it is hard for me to tell someone that they are HIV-infected and need to start lifelong medications. While we can treat HIV with effective once-daily medications, I would prefer to get to the root cause of the problem and stop new infections all together. As an HIV vaccine researcher, I feel that our work has real potential to transform the trajectory of HIV, and I get to work with inspiring and committed colleagues and volunteers.
I went to Brown University and Brown Medical School.
HIV was created by the government! Okay, not really. But on a serious note - how much does the government fund HIV vaccination research?
Since 2001, global preventive HIV vaccine research and development investment has totaled US$8 billion, with an average yearly investment of US$824 million. I don't know exactly how much the U.S. governemnt contributes but public-sector funders (such as the governement) provide the largest part of the investment, followed by the philanthropic sector and the commercial sector. For more specific information look at this report from The HIV Vaccines and Microbicide Resource Tracking Working Group
If (or probably when?) a vaccine is made, how expensive would it be? Would poorer African countries be able to afford it?
We still don't know what the cost and delivery of an HIV vaccine would look like. If and when we find an HIV vaccine, how it will be paid for and distributed will be important questions. Just as with antiretroviral drugs, how a vaccine would be distributed among the poor will probably depend on the availability of governement and philanthropic funding and on the work of activists, advocates, and others who can impact global health policies.
Do you know of any good books or resources on HIV etiology (I think that's the right word...) that wouldn't be too difficult for a layperson to understand?
It sounds like you're interested in good, easy-to-understand resources on HIV/AIDS.
There's a free, online course on Coursera focusing on AIDS that will be starting in Feb.: https://www.coursera.org/course/aids
The San Francisco AIDS Foundation is another good resource. Their website has a lot of good information, for example, this primer on HIV: http://www.sfaf.org/hiv-info/basics/
There's a lot of other good resources out there. Perhaps other people here might have some suggestions?
What is the closest thing found to the 'ultimate cure' and how did you come about on this?
What is the unknown that could be dangerous if in the wrong hands?
What surprised you the most to find while researching?
What accidental discovery, if any, has most helped you and your team advance the research?
- I work in HIV prevention, but there are many smart people working on a cure. Cure research is focused on finding out where HIV hides, and stimulating HIV out of its hideouts so that it can be killed.
- I am not sure what you're asking.
3 & 4. The results of the RV144 trial (which included 16,000 participants in Thailand) have been the most surprising to the field and also the most galvanizing. RV144 combined 2 vaccine candidates that had been previously found to not be effective when tested separately. However, the trial found that when these vaccines were used in combination there was a 31.2% decrease in HIV acquisition in participants who received vaccine compared to those who received placebo. Now researchers are working on figuring out what led to this finding and how we can improve this response. Specifically, we are looking for correlates of protection provided by a vaccine.
Why are some things so much easier to cure than others? I know how some things work if memory serves me, e.g. a cold constantly changes its never the same cold, the protein layer on the surface changes (i think) but you get the general gist of my question.
What is the biggest problem facing finding a cure to HIV?
We need to differentiate between an HIV vaccine (could prevent HIV in an HIV-uninfected person) and a HIV cure (could eliminate HIV in an HIV-infected person). HIV vaccine research is especially challenging due to the ability of HIV to evolve rapidly and evade our body’s natural immune responses. HIV cure research is especially challenging because during the early stages of infection, HIV establishes reservoirs of infection that will persist despite treatment with antiretrovirals.
i'm interested in how you test the validity of the data. do you use placebos as a control group?
i knew a couple of researchers who were working in a vaccine to prevent mother-to-child transmission, which was successful, however they had to have a placebo control group, which was a huge ethical question mark since they knew these kids will more than likely be born with HIV. what is your take on this whole thing? is that an acceptable thing for you?
That's a really great question. We do use placebo vaccines (usually saline) in our research. But we also make sure that we provide all of our volunteers with state-of-the-art prevention care, including regular risk-reduction counseling, free condoms, and testing and treatment for STDs. What we've seen is that many of our volunteers actually reduce their risk during their participation in the studies. The bottom line is that we are testing vaccine candidate that have shown positive data in lab and animal studies, but we don't know if the vaccines will work in humans (that is why we are doing the study!) .
Thank you for doing this AMA and for doing what you do. :) Not sure if you are the right person to answer my question but: Assumed there will be an effective HIV vaccine, would it be (too) expensive to mass-produce?
Great question. The cost and delivery of an effective HIV vaccine remains unknown. Typically, once a vaccine is found to be effective governments, international organizations, and private companies work together to pay for and scale up production and delivery of the vaccine.
If I understand the word "vaccine" correctly, that implies that you are working on a way to prevent HIV- people from contracting HIV. This is in contrast to a "cure" which would effectively eliminate the virus from HIV+ individuals.
In your opinion is more attention being given to discovering a vaccine as opposed to a cure with the assumption that a vaccine will eventually reduce the infection rate to almost nothing as the infected die off?
BTW, I would also like to thank you and all your colleagues for your work in the field. You are unsung, tireless heroes.
Yes, your understanding of vaccine and cure are correct. At this time, the fields of HIV prevention and treatment are more aligned than ever before. We want to treat as many HIV-infected patients as possible with antiretrovirals in order to suppress the HIV in their blood and we also want to find an effective HIV vaccine that prevents HIV in HIV-negative individuals. We do not know if a successful HIV vaccine will be 100% effective, so we need to keep up our efforts in both prevention and treatment for a very long time to come.
from the progress made do you see a viable cure or vaccine coming through in the next 5 years?
It will likely take more than 5 years for a candidate cure or vaccine to be licensed given the time it takes for appropriate clinical testing.
Are you working on a vaccine that would work like the chicken pox vaccine?
If a HIV vaccine was created, who get the vaccinated and at what age?
There are a number of different HIV vaccine candidates that are being developed, and they work in different ways. The big difference between the HIV vaccines we work with and the chicken pox vaccine is that the chicken pox vaccine uses a live attenuated virus - basically a weakened chicken pox virus. Due to the risk of mutation and reversion to a pathogenic form, we do not work on live attenuated HIV vaccines.
This is a question that we will need to answer if and when we find an effective vaccine.
Research in a specific field often has positive externalities (think of the advancements in technology thanks to space exploration). What are some of the other benefits that have come from HIV research (e.g, better understanding of viruses, better vaccines for other viruses, etc...)?
Many, many thanks for your dedication.
Cancer research is catching onto several lessons learned from decades of HIV research, particularly the importance of combination therapies. Read more here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3465702/
Do you use "live" viruses in your research? If so, what precautions do you take to protect yourself, the lab, the public etc. Is it any different from a normal virology lab?
Reverse Transcriptase inhibitors are fairly common antivirals - what are your thoughts on making a vaccine against RT? Would it be possible? Would it act against all retroviruses?
Due to the risk of mutation and reversion to a pathogenic form, we do not work on live attenuated HIV vaccines.
Hi, I'm a Master's student and I'm planning on going to medical school in the near future. However, I have a gap year in between graduation and the start of medical school while I apply. I have always wanted to work in a laboratory focusing on HIV research. I have about four years of laboratory research at labs such as the Centers for Vaccine Development, SRI International Centers for Advance Drug Research and from my undergraduate career. Are there any positions available to work with you?
It sounds like you have some solid research experience. But most of the work my colleagues and I do are in clinical research, though we do work closely with the AIDS Research Institute at UCSF. If you're still interested in working with us, you can always check out our careers page. We also work with the HIV Vaccine Trials Network, and they may have programs that might interest you. For example, the RAMP program funds African-American and Latino medical students to work on HIV vaccine-related research under the mentorship of an experienced investigator.
Hi--thanks for your willingness to share your knowledge.
I'm really curious about (and have been wondering for a while) about Timothy Ray Brown, and his apparent "functional cure". This is a case that you're surely (much, much) more familiar with than I. Can you explain: what a "functional" cure is at it is understood here, and as opposed to a cure? And can you clarify why this functional cure has not translated into a broadly usable cure?
You are referring to a highly publicized case report from Germany known as the “Berlin patient”. A 44 year old HIV-infected man (from the United States) developed acute myeloid leukemia (a cancer of the immune system) in 2007 and underwent a stem cell transplant from a donor with an inherited CCR5 delta mutation. CCR5 is a coreceptor on cells that allows for HIV to infect cells, persons who lack this coreceptor are less likely to become infected with HIV. Although the “Berlin patient” has had a complicated recovery requiring intense chemotherapy and radiation, nearly 4 years after discontinuing antiretroviral medication he has no evidence of HIV infection in his blood. However, we are not sure if HIV is lurking in cells found in the lymph nodes or other parts of the body, such as the brain, gut, liver, kidneys, and heart. Time will tell.
To summarize, a sterilizing cure is the eradication of HIV from the body. A functional cure does not eliminate the virus but allows a person to remain healthy without antiretroviral drugs.
While this may not be a true “sterilizing cure” it gives us great insights into developing HIV cures that involve transferring the CCR5 mutation to HIV-infected patients without the toxicities associated with stem cell transplantation.
Is it true that a certian HIV virus might be able cure cancer?
This is not really my area. But I did see some articles in the news about this earlier this month, for example, there was an article in the New York Times.
Again, I'm not an expert, but it sounds like they used a modified form of HIV in an experimental treatment for a child suffering from leukemia. As part of its life cycle, HIV inserts genetic material into the nuclei of human immune cells. It sounds like they used this feature of HIV to reprogram some of the patient's immune cells to attack the cancer.
What do you make of distributed computing projects like [email protected] or [email protected]?
I work in clinical, not basic, research, so I don't really use computing tools like these. But they sound like great ideas.
Please discuss the argument that HIV does NOT cause AIDS?
Could you also discuss some of the points raised in: http://www.naturalnews.com/027922_AIDS_David_Icke.html please?
The scientific consensus is that AIDS is caused by HIV. We also know that the major way that HIV is transmitted is through sex.
We have many strategies we know work to prevent infection by HIV, including condoms, using clean needles, testing and treating for STDs, and now, using medication that has been shown to be effective in prevention. We also have very effective treatments that can prolong the lives and protect the health of HIV-infected patients. Treatment can also lower the amount of the virus in a patient's body, making it less likely that they will pass the virus on to others.
Isn't it bad for pharmaceutical companies to release a vaccine for HIV, when there's so much money being made with HIV medications?
At Bridge HIV, we're committed to wroking towards a safe, effective HIV vaccine that will be accessible for everyone. While we sometimes work with pharmaceutical companies, the bulk of our funding is public, for example much of our funding comes from the National Institute of Allergy and Infectious Diseases (NIAID) of the US National Institutes of Health (NIH).
But even if we find a vaccine, there will still be HIV-infected people who will need treatments that are marketed by pharmaceutical companies.
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