One of the surprises at CROI 2016 was the first virological data from a new highly potent NRTI that in a slow-release formulation has the potential for annual dosing and that is undergoing research as both treatment and PrEP.
In an oral late-breaker, Jay Grobler from Merck presented results from a dose-ranging study in macaques to develop a model for phase 1 studies with MK-8591 (EFdA).1
Baseline SHIV viral load ranged from 6 to 8 log copies/mL and following single doses that ranged from 3.9 to 18.2 mg/kg viral load dropped by approximately 1.5 logs and was sustained for seven days.
PK data from a phase 1 multiple-dose study in HIV negative adults (using 10 mg, 30 mg and 100 mg) once-weekly for three weeks showed that with the 10 mg dose target intracellular target drug concentrations were exceeded for more than seven days.
A slightly cheeky slide was shown from the phase 1b study showing that EFdA produced more rapid viral suppressions compared to historical data for TDF and TAF.
Early data on a solid-state slow release parenteral injection formulation that has an option for removability, showed sustained release for more than 180 days in rat studies, with the potential for cover to be extended to a year.
was -0.4 (-4.7, 4.5) mL/min, eGFR-cystatin C 3.8 (-4.8, 11.2) mL/min/1.73m2, and aGFR (n=32, 68.8% TDF at baseline) was 0.1 (-4.3, 4.4) mL/min, indicating that GFR was not affected by E/C/F/TAF. Two subjects (0.8%) discontinued study drug for decreased GFR by eGFRC-G and eGFR-cystatin C, neither with evidence of renal tubulopathy. The prevalence of clinically significant proteinuria (UPCR > 200 mg/g) and albuminuria (UACR ≥ 30 mg/g) decreased from 42% to 21% and 49% to 27%, respectively. Significant decreases in urine retinol binding protein to creatinine ratio, beta”‘2”‘microglobulin to creatinine ratio, and fractional excretion of uric acid were observed (p
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.
With Dr Joel Palefsky and Jeff Taylor
everybody. Nelson Vergel, Director of Program for Wellness Restoration, a
nonprofit that focuses on wellness and health in HIV-positive people. We are
very honored today to have Dr. Joel Palefsky. He’s probably the world’s most
renowned expert in HPV infection in HIV+ patients. He’s got over 250 papers
published on the topic. It is a huge honor to have him be part of this Google
They are part of our educational efforts to bring the different topics to the
a very anxiety-producing topic we’re discussing today, HPV-related cancers in
HIV. I’m HIV-positive myself, being so for 33 years or so.
been diagnosed in the past with high-grade anal dysplasia. We’re going to talk about what
that means in the this hangout. It’s been a very high anxiety-producing problem
for not only me, I had two friends who have died of anal cancer-related
problems. In a few minutes we will also have Jeff Taylor join us, another
activist like myself, who has also dealt with the issue. He’s joining us soon.
I think a lot
of people don’t want to talk about it because we tend to avoid what causes
anxiety. We tend to get into denial very easily. Even though some of us have
dealt with HIV virus for so many years, we tend to not talk about anal
dysplasia or anal cancer. The doctors seem to also not be very trained on this
subject. That’s another barrier.
Palefsky, could you give us a little bit of a brief background of who you are?
I know your bio is like two pages long.
Well, thank you firstly for having me Nelson, it’s a pleasure to be here and
I’m really happy to have the opportunity to talk about this very under talked
most important thing about me. I’m trained in infectious disease. I’m actually
an infectious disease doctor. I’m not a cancer doctor. I’m actually Canadian. I
grew up in Montreal and I trained at McGill University in Montreal. Then I went
to the United States mostly to avoid winter, trained in infectious diseases at
Stanford and after Standard I became a professor at the University California
of San Francisco, UCSF, where I have remained till this day. I’m really an
infectious disease trained doc but a lot of my work has spilled over in the
cancer arena because of the issues that you raised. Much of my work is in the
cancer center at UCSF. One of the other very important thing that I do is, I’m
the HPV working group chair for the AIDS Malignancy Consortium, the AMC, which
is the consortium that’s very much like the ACTG but it’s run by the National
Cancer Institute and serves as the infrastructure to perform some of the
studies on anal dysplasia and other HIV related malignancies. One of those
studies will be the anchor study that we’ll be talking about later.
I should hang up?
Jeff. I guess Jeff Taylor. Jeff we can hear you now.
there you go.
Sorry about that. I didn’t mean to interrupt.
A little blurry but I guess we can see you. Maybe you can get closer to the
camera. I’m sorry, Dr. Palefsky was introducing himself. We were just telling
the audience how honored we are to have such an expert. I sort of kind of
introduced you Jeff. Can you tell the audience who you are and what your
relationship is with the AIDS Malignancy Consortium and all the work that you
do with HIV.
My name is Jeff Taylor. I’m a long time HIV activist and long time survivor,
30+ years with HIV and I currently live in Palm Springs. For about 15 years
I’ve been one of the community representatives for the AIDS Malignancy
Consortium, which I’m sure Dr. Palefsky described and for much the time Dr. Palefsky
and colleagues have valuable been trying to do HPV research and to get the
study up. It’s taken them at least a decade if not longer from perception to
finally getting the study open, which is the main reason as in anal cancer
survivor that I’ve joined the group.
really gratifying to see this research finally get done. I’m really committed
to changing the standard of care so that people living with HIV have access to
cancer screening, which currently is not universal and that needs to change.
so why don’t we start with the basics. I think some people watching this Google
Hangout may have no idea what HPV is. I will invite Dr. Palefsky to probably
just give us a HPV 101.
of HPV 101 at the risk of sounding a little bit self-serving. I did publish a
book for the general public a number of years ago which is still available
through Amazon, called What Your Doctor May Not Tell You About HPV and Abnormal
Pap-Smear’s, if you have any lingering questions, it’s pretty out of date with
respect to certain items like vaccination cause they haven’t let me update it.
The basic facts of HPV and how you get it and what you can do to prevent it are
written up in some detail for the general public.
HPV is a small virus which is only found in the skin. It only infects skin
cells, so the only way you can get the infection with HPV is through skin to
skin contact. Most of the time that’s through various form of sexual contact
though it does not have to be. Most people say that if you’re sexually active
you have 85% change of having at least one genital HPV type during your
lifetime. It is the most common sexually transmitted infection.
good news about it is that most of the time we don’t even know we have it.
Doesn’t cause any problems. What we think is probably happening is that you get
some changes in your skin due to the virus and if you have a healthy immune
system it fights it off and get rid of the cells that show changes because of
the virus so that if you’re getting checked by your doctor by the time next see
your doctor or other healthcare provider you won’t find anything, so they think
nothing ever happened. For the most part nobody is any the worse off.
is the situation. Most of the time that’s not the situation if you’re
unfortunately amino compromised. I think what is happening here is that those
85% of people, even though they never developed a sign of disease due to the
virus, probably keep small bits of the virus hanging out dormant or latent is
the word that we use. For most people causes no problems at all but if you’re
amino compromised then that dormant virus could reactivate and then develop
some of the skin changes that are of some concern.
are those skin changes? One of the common things that can happen with HPV, is
you get warts. You get warts on your penis, around your anus, on the inside of
the anus, if you’re a woman you can get
them on the vulva or inside the vagina. Warts are a major nuisance, very, very
unpleasant. They generally do not progress to cancer, so they are not usually
fatal. That’s the good news.
other tract that the virus can take instead of turning into warts is what we
call high grade squamous. Squamous is another word for skin. Intra-epithelial,
intra meaning inside, epithelial also meaning skin. Lesion meaning abnormality.
High Grade Squamous Intra-epithelial Lesion, I know long word and that big
tongue twister is just a basically a long word for pre-cancerous lesion.
reason it’s important to know it, is because the reports that you get from your
providers are going to use some of these words and it’s good to have some
understanding of what they might mean. Other words you might hear other than
HSIL are moderate or severe dysplasia where dysplasia means abnormal growth.
Another term you might here is anal intraepithelial neoplasia, usually we say
grade 2 or 3 are the cancer causing or the pre-cancerous lesion.
any of those AIN 2 or 3, moderate or severe dysplasia or HSIL, have the
possibility to turning into cancer if you leave them alone long enough. The
good news there is that not everybody that gets HSIL does develop cancer. In
fact in the setting of HIV are best guess, this really is a guess, roughly 1/2
of people that are HIV positive will have an HSIL lesion in the anus. That’s a
really big number but only a fraction of those folks will go on to cancer but
that fraction because the denominator is so big is too high and our best guess
is roughly 10% of people who are men who have sex with men, MSM, and that are
HPV positive will develop an anal cancer over their lifetime.
just a guess. So, almost everybody gets HPV, about half of people, when I say
everybody I mean HIV positive MSM, 90% of HIV positive women will get HPV in
the anus, 60% of HIV positive men that have sex with women will get anal HPV,
roughly 50% of HIV positive men who will get a high grade lesion, HSIL, we
guess about 20%-25% of women who are HIV positive will have an anal HSIL. We
don’t really know how many men have sex with women at this point, we don’t have
enough research yet, but only a fraction of those individuals will develop into
an anal cancer. HSIL by itself is not dangerous, we don’t really care that much
about it unless its causing symptoms such as burning or itching, occasionally
on the outside of the anus, it can also be unsightly which can be disturbing to
people but generally its asymptomatic and people don’t even know they have it
and it’s not dangerous until it becomes cancer.
when it becomes cancer, what’s happening is that the cells which are sitting on
the floor of the skin, the structure that is the floor of the skin is called
the basement membrane and as long as the cells stay above that basement
membrane it’s still intraepithelial and not cancer. The moment the cells punch
through the basement membrane down below and start to spread either locally or
to some of the distant organs like the lungs or the liver, then by definition
it’s cancer and that is what kills people. It kills people by spreading locally
and blocking some of your vital organs in the pelvis or it can replace a lot of
your liver or fill up your lungs and do all kinds of bad things.
mortality is when that happens. If you have HSIL and no cancer it will not kill
you but the concern is that some of these do progress to cancer, so the
question is what if anything can we do to try and reduce your risk of
progression to cancer. There’s two generic answers to that question. I don’t
know if you’re ready to launch into that yet Nelson.
let’s do that. That’s a good transition.
We have what we call primary prevention and secondary prevention. Primary
prevention is basically vaccination against HPV. It’s called primary prevention
because what you’re doing is not preventing the disease but prevention the
acquisition of the agent that causes the disease, so in this case you’re
preventing getting HPV. This is a preventative vaccine that you should take
ideally before you’re exposed to HPV because it really works best only in
prevention mode. If you’ve already been exposed to HPV types and the vaccine
really won’t do you any good.
we move on, when you say HPV types, can you tell us, there’s more than one HPV?
So there’s many types. There’s more than 200 actually. Only a subset of those
affect the genital region and only a subset of those cause cancer. We have what
we call high risk types also called Innogenetics cancer causing and low risk
types which are Non-Innogenetics. The low risk types the most common are type 6
and 11, which are the types that cause warts, which as you recall do not
ones that worry us more from a mortality point of view are type 16 and 18 These
are the two most common Innogenetics or high risk types. So the Quadrivalent
vaccine which has four types in it has type 6 and 11 in it to protect against
genital warts and type 16 and 18 to prevent a high proportion of the cancers.
very recently there’s yet one more version of the vaccine available called the
Nonavalent vaccine, Nona is Latin for 9. What the manufacturer of that vaccine
did was it took the four types that were already in the vaccine then they added
five more that also cause cancer and the proportion of cancers that would be
covered or prevented by this vaccine has gone up. If you take the nine valent
or Nonavalent vaccine instead of the
most HIV positive MSM, it really doesn’t matter which vaccine you take because
we think that the great majority of anal cancers that occur in HIV positive
people are due to type 16. The addition of the five other types probably
doesn’t matter all that much. Still if you have the availability of the nine
valent vaccine, I would probably take that if you have the four valent that’s
telling us it doesn’t matter if you’re gay, straight, top or bottom, right?
do we know if we have those HPV types and whether or not the vaccine, either
one of those vaccines will help us?
question so generally we do not test people before to decide whether or not
they should get the vaccine. There are no commercially available test to tell
you whether you’ve already been exposed to this or that HPV type at least for
men. There’s no blood test commercially available. There are blood test to see
if you’ve had antibodies before but they’re primarily for research. They’re not
approved for clinical use. The only commercially available HPV test that is
approved by the FDA or the detection of HPV is for women in the cervix. There
are no FDA approved anal tests.
the decision to get vaccinated is primarily based on age where the target
group, the ideal time to get vaccinated is in the 9-11 age group because you’d
ideally like to get protected before you even start having sex. The more sexual
partners you’ve had, statistically the likelier you’ve been exposed to one or
all the HPV types in the vaccine. The next big thing after the 9-11 age group
is get vaccinated before the age of 21. Then if you’re an HIV positive person
or a man who has sex with men you are also approved by the government to get
vaccinated up to age 26. The reason it’s an important number isn’t because
there’s any magic about 26, it’s not like the day you turn 26 you become a bad
vaccine candidate, it’s just statistics and the government and the insurance
companies tend to use that number to decide who they’re going to reimburse for
the vaccine or not.
might be a perfectly good vaccine candidate the day after you turn 27 but you
may have to pay out of packet if you choose to have the vaccine. That’s the
general, again, these are generalizations. The fewer number of sexual partners
you’ve had the likelier you are to benefit from vaccinations. I often get asked
by my patients who clearly have signs of HPV disease when they come to see me,
“should I get vaccinated?” and the answer I give them is maybe. The
primary reason being, while we don’t know that its going to help them because
they may already been exposed to some of the HPV types and the vaccine. They
might not be exposed to all the HPV types and the vaccines so they might still
benefit from the protection against those and the vaccine we think is pretty
major downside really is to their pocketbook and their finances because it’s
not a cheap vaccine.
requires three right? Three boosting shots.
So it’s 0, 2 and 6 months. Three different injections. If you’re younger and
not yet in puberty your immune system is a little stronger and we think that
for those individuals it may be possible to just get two vaccinations but not
for most of the people who I think are listening to this webinar. So three
vaccinations really is the standard.
is the cost of the vaccine Dr. Palefsky?
that’s a little hard to say because it depends very much on the setting but
generally you can expect to pay at least $100 for every injection and probably
Houston it costs $250 to $300 every injection
So it’s not a trivial decision. There’s also some very early evidence, very
preliminary I would emphasize that suggest if you are being treated already for
an existing HPV lesion, that if you get vaccinated on top of that, then it
might, I really emphasize might, reduce your risk of recurrence because that’s
another big issue which perhaps we’ll come back to but once you get treated for
HPV, when you’re HIV positive, there’s a pretty big change another lesion is
going pop up somewhere else or that you might get a recurrence of the lesion
that was treated.
a possibility that if you get vaccinated that it might reduce the risk of that
happening but we really don’t have good evidence yet.
all that’s to say, that’s what we call primary prevention trying to avoid
getting HPV in the first place. If you don’t get HPV, you’re not going to get
HSIL and you’re not going to get cancer, it’s that simple. Now that’s not
simple, unfortunately, and most of us have already started having sexual
activity well before the vaccine became available. Many many millions of people
would not benefit from the vaccine just because of what they’ve done prior to
the advent of the vaccine.
those individuals we have what’s called secondary prevention. Here the goal is
not to prevent acquisition of HPV, it’s rather to prevent progression of lesion
that might occur due to HPV before they can turn into cancer. A very good
example of this is, is the cervical pap smear system. Many of the listeners
will be familiar with cervical pap smears. Either you have had them or women
who you know and love have had them. Your moms, your sisters, it’s standard of
care for women to get a swab of the surface of the cervix which is very much
like the anus to look for cellular changes in the swab material that reflect
the presence of HPV and show some of those pre-cancerous changes that we talked
cervix is just like the anus in that you can get HSIL in the cervix and
overtime it can progress to cervical cancer, which again is a similar disease
to anal cancer. So what we know now from decades and decades of experience is
that if you can screen for those cervical pre-cancerous changes with a pap
smear which is basically just a swab or brush and then if it comes back
abnormal you go looking for those lesion’s using a device called a colposcope
or a microscope to find the source of those abnormal cells on the cervix and
then you find them and then you take a tissue sample to see how severe the
abnormality is. If it has HSIL then the next step would be to remove that HSIL
lesion in the hopes of doing so before its progressed cancer.
that to say when you do that and remove those HSIL lesion’s it does not
completely prevent the development of cervical cancer but it very dramatically
reduces it. Since we started doing this pap smear screening in the cervix, the
incidence of cervical cancer is come down by 80% but it’s still there but it’s
a very one of the most successful public health measures we’ve ever had.
since HPV causes anal cancer just like it does cervical cancer and HPV causes
anal HSIL just like cervical HSIL. We’ve been thinking for many years now that
if we look for and remove the anal HSIL’s, that perhaps we can remove or reduce
the risk of anal cancer. Entirely if you pardon the expression inelegance.
don’t make any jokes. We’ve never have anything funny to say in this business.
that’s not true, but out of respect for the sensitivity of the listeners, we’ll
probably refrain from some of the saucier ones. At any rate, though at UCSF we
started the world’s first clinic devoted to that principle, it’s called the
Anal Neoplasia Clinic Research and Education Center or ANCHOR as opposed to the
anchor study that we’ll talk about in a bit which is anchor like the ship. The ANCHOR
clinic was established to look for signs of HSIL in patients referred to us and
then remove those lesion’s in an effort to prevent them from getting anal
would think based on everything I’ve told you that it seems like a no brainer
that obviously anybody’s at high risk of having anal HSIL to just go and get
their anal pap smear. Just to be scientific here, we don’t actually call them
anal pap smears even though that’s what they are because pap smear is a term
that really belongs to the cervix. Though the word that we use, the medical
term is cytology, cyto means cells in Latin. All we’re doing is looking at anal
cells and what we’re doing is basically inserting a moistened swab inside the
anal canal and sort of vigorously swishing it around in an effort to dislodge
cells from the surface of what is essentially a tube that has the skin that HPV
can effect and cause the lesion’s in. All we’re doing is taking a random
sampling of the cells from the surface and then looking under a microscope to
see if they have any of the changes that might indicate the presence of HPV and
one of those high grade lesions.
been doing anal cytologies on high risk people and anybody whose had sex is at
high risk, specifically anal sex and if you’re HIV positive you’re at high
risk. Many but not all of our patients are HIV positive. Many are men who have
sex with men but not everybody. I have a lot a women in our clinic as well.
the idea then is we would then do a technique called high resolution anoscopy
or HRA for short and this is a technique that is again very similar to what
women have when they’re looking for the changes in the cervix if they have an
abnormal cervical pap smear.
to take you through the sequence a little bit first, after you’ve had your anal
cytology swab done if you were to visit us in the ANCHOR clinic the next thing
you’d have done is a digital anal rectal examination. You’ve may have heard
different terms for that. You may have heard it called digital, maybe you’ve
heard it called DRE or digital rectal exam. We’re trying to change people’s
thinking about that test, it’s not a rectal exam, it’s an anal exam. The rectum
is not the same organ as the anus, it’s above the anus. If this is your anal
opening, I’m going to turn it a little bit here and if this is the outside,
then the anal canal is here and then above that is the rectum.
a very important distinction because only the anus can be infected by HPV not
the rectum. If somebody truly has rectal cancer, it’s a very different disease
from anal cancer. It’s not associated with HPV. Anal cancer is associated with
HPV and when we’re doing a digital exam, basically what we’re doing is feeling
in the anal canal for changes that HPV may be causing in the anus. If you’re a
man, we’ll also feel for the prostate but we’re not focused on finding rectal
cancer, we’re not really focused on finding prostate lesion’s. We’re primarily
feeling for very hard lumps that might indicate the presence of an abnormality
in the anus which could prompt concern for anal cancer.
we call it a DARE, Digital Anal Rectal Exam. I think one the most important
messages I want to give today to the participants in this session is that if
your provider does not do anal cytology or high resolution anoscopy, which is
probably true for most of you the least you can assist upon is having an annual
Digital Anal Rectal Examination. Every doctor has been trained on how to do a
digital exam and it should be, it has been but we’ve been getting away from it
lately, it should be part of a routine examination at least annually for HIV
doctor or the provider, whoever they may be should put on a glove, should put
on lots of lube, ideally even with a little topical lidocaine cream mixed in
with KY and then they should take their time and feel around very methodically
in all directions because it’s a 360° tube. Thought it should not be in and
out. It should be a very careful sweep, even multiple times to feel for things
that might be suspicious.
that is done, then we will proceed with a High Resolution Anoscopy. This uses a
piece of equipment called a colposcope which is the equipment that gynecologist
use to look for these changes on the cervix. What the colposcope is, is
basically a rolling microscope. We don’t call it … In the cervix that
technique is called colposcopy. We don’t call it that for the anus because
colpos means vagina and so we don’t think it’s appropriate for use for the anal
area so we call the same technique high resolution anoscopy.
we do is we take a small disposable plastic anus scope, many of your
participants will have seen those before, they’re kind of [stainless:31:49]
which you have inserted if you’re looking for clap or Chlamydia or whatever in
the anus. You put that in, we apply vinegar, 5% of acidic acid, plain old
vinegar because it turns some of those lesions like HSIL, white. We’re looking
for whitening. We apply vinegar into the anal canal and you may ask yourself
how do you apply vinegar inside the anal canal and here what we do we put that
disposable plastic anus scope in, we wrap a stick with gauze that has been
soaked in vinegar and then we put the stick in directly through the anus scope.
Then we pull the anus scope over the stick, so that the stick is sitting inside
the anus directly. Should be in there for about 2 minutes or so and then we
just pull out the stick and then we reinsert the plastic anus scope and bring
that rolling microscope up to the opening of the plastic anus scope. We don’t
insert anything else into the anus. We’re not putting colposcope into the anus.
just rolling it, so that I can visualize very clearly the appearance of the
skin through the magnification that the colposcope brings along with the
whitening that the vinegar shows and we’re looking for different kinds of signs
of HSIL, not only the whitening of the vinegar but also blood vessel patterns
and the geography and all kinds of clues. We also sometimes apply an iodine
solution called lugol solution to the surface of the skin because that can
provide us more hints that an area might have HSIL. Really what we are doing
when we’re doing this high resolution anoscopy is looking for the worse most
advanced changes we can find.
goal is to take a tissue sample or a biopsy of that to decide whether you have
HSIL and also to make sure you don’t already have cancer. When we take a
biopsy, we’re taking a very tiny specimen, we say it’s the size of a sesame
seed. If it’s high up enough which is most of the time, you don’t even need any
form of anesthesia because what most people don’t realize is that part of your
anus doesn’t even have sensory or touch receptories, it does have stretch
receptories. That’s how you know you have to poop or that’s some of the
sensation you have if you’re having intercourse but you don’t really have
feeling like touch. We can actually take small snippets without causing much
pain or any pain.
a anal biopsy is quite simple. If you have on the other hand abnormalities
close towards the outside or on the outside part of the self then you should
have a small injection to numb it or freeze it, prior to having a biopsy.
Basically we take the biopsy and then we bring in the patient back after we get
the results because it usually takes a few days to get the result of the
the person has no high grade disease, we usually can follow them up. If they
have cancer, which we hope of course they don’t that will prompt a certain set
of actions that need to be taken to treat the cancer. If they have high grade
disease then we will talk about ways to remove those high grade lesions to
reduce the risk of cancer.
one thing that is very important to understand is that this whole system which
I told you is modeled after the cervical system is predicated on the assumption
that it works. We know it works in the cervix so we assumed that it would work
in the anus too but we don’t actually have any proof of that. We don’t know for
sure that when we treat these lesions that we are really reducing the risk of
anal cancer. If you’re my patient and you come to me and I find high grade
disease in you, I’m going to treat it, I’m going to remove it and lets say five
years from now you don’t have cancer which is of course what we hope, the
problem is I can’t say with certainty that you didn’t get cancer because I
treated you. It’s conceivable that you might never develop cancer even if I
didn’t treat you.
can’t prove to anybody including the people who pay for this procedure, the
insurance companies or the government through Medi-Care, Medi-Cal or Medi-caid,
that I’m doing something useful. Even though we think we are, we can’t prove it
and so this is one of the reasons why it’s not standard of care everywhere
because if you live in a small town in the middle of the Mid-West and you go
and ask your doctor to do this for you, first of all he or she is not trained
and it takes a lot of training to get good at high resolution anoscopy.
me stop you right here because I think it’s important. I understand your group
trains doctors in … I saw a few years ago, Jeff actually posted this in one
of our forms, there’s a list of doctors or is that list public information.
Somebody can find out where doctors in their area.
a list of doctors who have agreed to have their names posted as being
available. Now it’s not a list of doctors who are signing off on, saying
they’re good at what they do because we don’t know everybody. These are just
people who self-identify as being available to see patients. There’s a couple
different places where people can go and see that list and probably isn’t quite
the same list at the two place but one of them is our website UCSF and the
other is the website for the International Anal Neoplasia Society.
website I can give you. It’s www.iansoc.org
for UCSF is what, the ANCHOR.
would good the ANCHOR clinic at UCSF and it will give the website I don’t have
it memorized actually.
I want to stop right here and give Jeff Taylor a chance, before we move to the ANCHOR
study. If that’s okay with you Doctor.
has a … I have a story of my own but I think Jeff has a story that will
probably compel people to get more involved and be more progressive and
proactive about their HPV disease management or diagnosis. So, Jeff can you
share with us in a very short time if you can, I know it’s a long story, your
story about not only being HIV positive but having issues with HPV.
Nelson. Well, 20 years ago back in ’96, I started like everybody else I started
on combination therapy. I had been really sick down to two T-cells, PCP, the
whole 9 yards and responded very well to therapy. My T-cells rebounded but also
also around this time I started noticing some changes in my anus. It was kind
of non-specific. At first I thought it might be herpes or something because I
had in the past but they checked it out.
I wasn’t quite normal and I heard of Dr. Palefsky’s work, so I asked my
physician who was very progressive about getting what they were calling an anal
pap smear and his response was that he could do it, he was willing to do it but
the lab wouldn’t accept a so called pap smear from a male patient. They would
not allow to be done. There was no way to get this test done where I was living
in San Diego at the time. Eventually, I got a raging case of condyloma warts,
went in and got that removed, they did a biopsy and it came back with what they
called AIN-4 or NC2 of Carcinoma which is early non-evasive cancer.
got a really disturbing diagnosis of the doctor, he said, “Well, we’ll just
wait and see, we call it Bowen’s disease, this is a disease of older men in
their 60’s and 70’s. Progresses slowly, we’re just going to watch and
wait.” I said, “Wait a minute, I’m in my 30’s, I have HIV, I’ve got a
severely compromised immune system, that does not …
also been diagnosed with high grade dysplasia and I’ve gone through at least
five high resolution anaoscopy’s myself. I regret some of them, I’m just going
to say that out loud right now. I think I was, I was, because it was me, nobody
made me do it. I was a little bit over-aggressive. I never demanded surgery
treatment but it was obviously offered to me every time they found some more
spots. I do think I have more scar tissue than I should have.
my point of view, I was one of those believers that I believed you had to be
aggressive about everything in HIV. I look back and now I say, “Hm, now
I’m looking at the date” and Dr. Palefskyis going to probably talk to us
about remission data that we’ve seen on people that have not gotten their
lesions treated and they seem to naturally get better. That was news to me.
That actually opened my eyes to the fact of, maybe I was over-aggressive maybe
waiting and seeing is not as scary as it should be. We’ll talk a little about
this issue, it’s part of the ANCHOR study because they will be looking at this.
if we have you back online. It was a cliffhanger. We were getting into your
story. Basically you were at the point … You remember where you were right? I
hope you do, on your story before you froze.
Sure thing. Well let’s try this one more time. My doctor who diagnosed me with
the insitu Carcinoma wanted to watch and wait. I wasn’t happy with that, so I
asked around, found a good surgeon in LA who did the surgery again on my warts.
Cleared everything, cut it out, had to go through chemotherapy radiation and
ever since then I’ve been monitoring really close.
I’ve had that surgery twice since then. Once because warts came back, another
time because I had extensive high grade disease but it’s never come back and
that’s why I watching really carefully the research to see as you were just
mentioning if we can have the same good results without going the drastic route
and getting surgery. There’s a number of things that perhaps Dr. Palefsky will
talk about and interim ways to treat the high grade dysplasia without having to
you so much for joining us. Actually, Jeff is, I would say the #1 activist in
the United States working on HPV and HIV, probably one of the top also activist
in HIV itself. Thank you Jeff and we’ll talk later about that.
want to go back to Dr. Palefsky and talk little about this before we move into
the ANCHOR study – the data that I saw from I think from your group, on natural
remission. What are you seeing there? Also part of that discussion is
aggressive treatment like in my case, I am one of those patients that
aggressively went for the whole issue and have probably more scar tissue than I
should. Let’s talk about the remission first and then we’ll go into the second
question. I don’t want to ask two questions at the same time. So tell us a little
about what you see in there.
The data that you’re referring to, I think we’re not actually ours, I think
these are data that have been coming out of Australia. To be very frank with
you, we’ve not been seeing the same thing.
our experience, it is possible to see regression for HIV positive people but it
is not common. Just certainly fewer than 10% of people who are HIV positive
will have a spontaneous regression to nothing. What is probably happening in
most people is that they have a high grade lesion sitting there and it just
doesn’t change. If you did nothing, it may not progress to cancer but it
probably not going to regress by itself. That’s our sense. We actually had some
data coming out from a study we’re just finishing now, where we compared
infrared coagulation which is one of the treatment methods that we use to doing
nothing, at least over a period of a year and we’ll have a better sense of what
our true regression rate is by itself.
clinical impression, after following people now for over 20 years is that the
proportion that really completely disappear is quite small and it’s probably
related in parts to the amount of disease that you had to begin with.
one of those people who has a very tiny area of involvement, then if anybody is
going to regress, it is probably you. If on the other hand, you’re that person
who has a lot of disease, it might be in multiple places, it might be very
large, then I would say your chances of spontaneous regression are quite small.
about CD4’s? Do they matter?
don’t matter anymore in the ART era. In the pre-ART era, when the CD-4 was a
better marker of where you were [etymologically 00:47:57] definitely the higher
the CD-4 the better your chances of … Even then people with high CD-4 then
didn’t show much spontaneous regression but the risk of cancer was definitely
higher than people with lower CD-4’s. Now that many people are on
Antiretroviral therapy, the prognostic use of CD-4’s is not as good.
it doesn’t matter what t-cells you have, you should get checked too, okay.
see people who started off with very low t-cells, sort of like how Jeff was
describing, goes on antiretroviral therapy, it has a great response,
undetectable viral load, big jump in t-cells, maybe well over 500 and we still
see raging high grade disease in the anal canal. We do not see big time
regression of high grade disease, even on people who are doing very well on
Just moving on to the study itself, then.
don’t we go for it.
basically, in order for this to become standard of care we would like it to be
available to more people. The people who make these decisions, I think quite
rightfully said to us, “Show us the evidence that what you’re doing works.
For not only for economic reason for health reasons. We don’t want to do things
to you and you’re an example of somebody who says they have perhaps had some
side effects of the treatment. I don’t want to do something to you unless
you’re getting real benefit from it.”
only way for me to prove that I’m helping you when do these various treatments
is to do what we call a randomized controlled trial, where basically we take a
group of people with high grade disease and we randomize them 50/50 to one half
of you we say we’re going to treat your high grade disease the other half we’re
going to watch your high grade disease very carefully. One is called the treatment
arm, the other is called the active monitoring arm and we plan to follow people
for a minimum of 5 years and then at the end of the five year period we’re
going to count up the number of cases of people who developed cancer in both
arms to see if we’ve actually had an impact.
may be that we’ve had very little impact and if that is the case, we’re going
to stop doing what we do and try and find some other way of at least reducing
the morbidity or mortality from anal cancer. If we find that we are having an
impact, what we really hope of course, then that will compel the government and
others to recommend that this becomes standard of care for all high risk
to be clear it doesn’t have to be done for everybody, low risk people, people
who’ve never had sex, probably don’t have to worry about this.
are those? Who are them?
are them? [crosstalk 00:51:08]
not even monks.
are people who are low risk, you know who you are and there are people who are
at high risk and you know who you are and those are people that are HIV
positive and who have sex with men, women who’ve had Vulvar disease that’s high
grade or cancer, women with high grade cervical disease or cancer, people who
are amino compromised for any reason, transplants, medication to treat
arthritis that sort of thing. It’s not an insubstantial number of people but
it’s still a pretty well defined group of people.
to get into the study you have to meet certain criteria. You have to be 35
years or older. You could be a man or a woman, it doesn’t matter how you got
HIV but you have to be HIV positive. You could be a man who have sex with men,
man with sex with women, you could be a woman, transgender of course and
basically you should not have ever had high grade disease or cancer treated. It
is okay if you’ve been diagnosed with high grade disease before but if it’s
been treated before than you’re not eligible for the study.
if you meet this basic criteria and you understand that you have a 50/50 chance
of being in either of these arms, then you would qualify potentially for being
in this study. It is really important for people to feel comfortable being in
either arm because we don’t want people to go into this arm and say, “Oh,
I wish I was in that arm and I’m going to drop out of the study” because
that would be very bad for the study and
for addressing the scientific question.
work very hard to explain what the pros and cons are of being in either of the
arms and we want to be real sure that people are comfortable with the study and
that they’re satisfied if they’re in either of the arms. There are some people
who say, “Oh you told me I have a lesion that has a chance of progressing
to cancer, I want that thing out no matter what.” If you’re one of those
folks, then you would not be a good candidate for this study because you have a
50% chance of being put into a monitoring arm. You might be the kind of person
who says, “Well you don’t have any proof that you’re helping me and the
treatments have some side effects potentially. So, as long as you’re monitoring
me carefully, I would rather be just monitored since my chances of getting
cancer over the 5 years of the study are actually rather low.”
fewer than 1 in I think 200, will develop cancer. So that’s small, it’s not
zero but it’s small.
frequently are you going to monitor?
default is every 6 months but the person who is following you has the
opportunity to follow you every 3 months if they’re more concerned about you.
The good news there, if at one moment in time, let’s say today, I see you and I
don’t see any cancer but you come in 6 months from now and now I think you have
cancer, that means that in all likelihood that cancer could not have been more
than 6 months old. It is going to be a very early cancer. The good news is that
we think those cancers are usually pretty straight forward to treat. We think
that some of them, in fact, we’re about to start another AIDS Malignancy
Consortium study, may even be treatable at that very early stage by just
locally removing them the same way you would a wart and avoiding the very
serious chemo and radiation therapy side effects.
course we can’t guarantee that somebody won’t have a bad outcome like they
might even die but we think it unlikely and we think that the worst case
scenario in either arm, if you get cancer, your chances of successful treatment
if you’re being monitored very carefully should be very high. You should be
okay. You might get cancer in either of the arms because again we don’t know
that what we’re doing actually prevents the cancer. You may wonder why might
the treatments fail. The reasons the treatments might fail are #1 we’re dealing
with amino compromised group of people, #2 we often find that people have big
lesions, fairly widespread and it’s possible that we’re not even getting all
the high grade disease, even though we’re trying and so some of it might slip
through. There are any number of possibilities for why, even with our best
intentions we’re not able to prevent every case of cancer.
real question is, are we preventing enough cases of cancer by treating compared
with the active monitoring arm and that’s something we can’t know until we do
that comparison. When all is said and done, that’s what the ANCHOR study is
long is the study and how many people and how many sites?
a big study. Okay, we call it our big ass study. I have to take a moment to
give kudos to the National Cancer Institute now, specifically the office of HIV
Associated Malignancies, this is your tax dollars at work. The National Cancer
Institute has made an enormous commitment to this field. It’s not specifically
LGBTQ funding because the study is not just for LGBTQ but it is funding that
will benefit the LGBTQ community extensively and is probably the biggest,
single health research investments in the community ever.
NCI has indicated that they’re willing to give us up to almost $90 million
dollars to do this study, over roughly an 8 year period. So they made a very
big commitment to this.
your Congress person. It’s huge and we’re going to open this study in 15
different locations around the U. S. because it needs to be a big study.
Ultimately we plan to enroll a little more than 5,000 people with high grade
disease. Probably going to screen 15,000. Once people are proven to have high
grade disease on biopsy, they’re randomized and then they get put into one of
these two arms and then followed for a minimum of 5 years.
have a data safety monitoring board or DSMB, to whom we report the data on an
ongoing basis. We’re going to show them how many cases are cancer are
developing in both of the arms. They’re going to be the only ones who know and
they’re going to make recommendations as we go along as to whether we should
continue the study. It might be for example, we’re having such a profound
impact that we don’t have to wait 5 years, if we’re seeing a difference between
the two arms. If that’s the case then they’re going to say, “yeah, you’re
already showing enough a difference. There are pre-defining criteria, you can
stop the study now” and that’s what we will do. They may say, “No,
there’s still not enough of a difference between the arms, just carry on.”
what’s going to happen.
other thing that I wanted to tell people is, what I just told you is the main
focus of the study but there is another very important benefit and that is, we
will be collecting samples from people as we go along. We’re going to be
placing those samples into a tissue bank, it’s called the AIDS Clinical
Specimen Resource or ACSR, also ran by the Cancer Institute. The plan is to
collect these samples from everybody, so at the end of the study or maybe even
before, we’re going to have a well-defined set of samples from people before
and after they develop cancer. At least amongst the small subset of people who
will develop cancer.
are not going to be samples like that anywhere else in the world and there will
never be again a set of samples like that. These extremely valuable samples
will allow us to hopefully develop new tests that will tell us, this is a
person who got these changes in the cells that predict that they’re going to
develop cancer or not because at least half of everybody developing a high
grade lesion, I really wish I didn’t have to treat half of the whole population
to prevent the cancers. I would much rather tell you, if you have a high grade
lesion … “You have a high grade lesion but you don’t have one of those
changes, so I could just watch you, but you, you have one those changes that we
showed in the ANCHOR study were associated with progression to cancer within 6 months
or whatever. You’re the person who I really want to treat today.”
call these bio markers and the hope is to identify bio-markers that tell us,
which people with high grade disease need to be treated actively and which we
can safely follow. So you don’t have to have all that scar tissue, if you’re
not at risk of developing cancer. The other hope is that we can use the
information to develop new treatments.
they website to find out more information about the study?
www.anchor.org. I think that’s right. Might be anchordmc.org.
is one word that is really hard to buy as a website. It’s probably going to be
Anchorstudy.org. Okay and that’s all the inclusion, exclusion criteria, how to
join, where the different places are, right? Are listed there?
have a wonderful video that people should watch. Go to YouTube and look for
Anchor Study. There’s a wonderful, two minute introduction. The details
regarding enrollment criteria and what it means to be in this arm or that arm
are going to be posted soon. We developed a sequel to that video which will provide
more specifics about that. Should be available very soon.
I’m going to be posting all these resources on the comment section of this
video. This video, this Google hangout is going to be basically up, 20 minutes
from now, going to be available on YouTube and on the comment section you’re
going to see the websites, the names, the video that you just mentioning and
any other information that people need.
So I can tell your participants now where there are active sites in Anchor. At
the moment we have active sites in San Francisco. We have three active sites in
New York City, Cornell, Montefiore, Laser Surgery Care. We have an active site
in Chicago at the Mid-West Dysplasia clinic. We have an active site at the
Fenway in Boston and also at Boston Medical Center. An active site at Wake
Forest, actually in Winston-Salem, North Carolina.
we have several that are going to be starting up soon in the South. We’re going
to be opening a site in San Juan in Puerto Rico. A site in Atlanta at Emory.
We’re going to be opening a site in Denver. A site in Seattle. A site in,
hopefully in Los Angeles very soon at UCLA.
we don’t know yet about Palm Springs.
are hoping to open a site in Miami. Possibly a site in Houston. Possibly a site
in Chapel Hill and what am I missing?
be spreading them I’m sure, even more.
is enrolling right now, right?
study is open. It’s enrolling. Please if you’re interested go to the website.
There’s contact information for each of those sites and we promise to treat
everybody very well.
they need to bring records from their doctor or do you guys take care of that?
give you a list of the things that we’ll need. We’ll need documentation of HIV
status, primarily. Information about insurance and the usually sorts of things.
more question on related to the study because it really struck me as odd. Why
did you guys decide on the age of 35?
The reason is, anal cancer takes some time to develop and in fact in the
general population the mean age at which anal cancer develops is 62. Let me
give you an extreme scenario, which I think might make it clear. Supposing we
said to get into the study you need to be between 20 and 25 years old. If we
did that and we followed people for 5 years, the number of people who develop
anal cancer would be 0 and we wouldn’t be any further ahead.
need to follow people who are at risk of anal cancer because if in the control
arm or the active monitoring arm rather, if people in the active monitoring
arm, if nobody develops cancer then we can’t show any benefit in the other arm.
So really what we’re trying to do is enrich or a group of people who are at
risk of cancer, otherwise there would be nothing to study. Then, also by
enriching, we could reduce the number of people who we need for the study. We
want to obviously do the size of the study that we need to get the answer from
a statistical point of view but keep it as small as possible to control the
cost of the study and enrolling as few people as needed to do the study.
that make sense?
Yeah. Of course. For those who are under 26 and are HIV positive and high risk
they can talk to their doctor about vaccinations?
would say to anybody who is under 26, get vaccinated, I don’t care if you’re
HIV positive or HIV negative. If you’re an MSM, your 26 and under get
something trying to convey, especially now with the message around PrEP and
prevention of HIV. Now that a lot of MSM’s are getting into care because of
PrEP and they’re being seen every 3-6 months by their doctors, I’m not seeing
HPV discussion coming through that process. I’m trying to, a few of us are
really trying to take advantage of the prevention message or HIV and
incorporate the prevention of HPV disease.
more question. It has nothing to do with study but it’s really more global
question. Are you aware of any companies out there because I’ve been looking at
the research pipeline for HPV and they’re looking at and we’re getting really
close to ending this but I really need to ask this question.
really applies to people like me and Jeff and few of the old farts out there
that have been positive for long. Companies are actually looking at immune
based therapies that could probably treat people with that have many of the bad
HPV genotypes, anybody you know up there, in the pipeline.
So you’re talking about two things, one is what we call a therapeutic vaccine
instead of preventing it’s treating existing disease using an immune based
approach and yes there are companies looking into this and we’re planning
studies to do that. We’ve already done some while ago, they weren’t particularly
exciting but we think the technologies have improved and we will be doing a
study looking at whether we can inject people with these vaccines and hopefully
make the lesions go away that way.
there are some non-immune based approaches that people are looking at using
various creams and other approach like pills to hopefully treat the virus and
make some of the lesions go away. There’s nothing yet. These are very promising
sounding but we can’t know really until we try them but I think I’m modestly
hopeful that we might have something.
we have things for HIV. We have things for Hepatitis-C, Hepatitis-B and HPV has
been one of those that’s like what’s going on
anything that Jeff, do you want to add before we close because we’re really are
going much beyond the 1 hour. We’re at 1 hour and 15 minutes. Anything you
wanted to add?
I mean I think the take home message here is anybody, gay or straight, positive
or negative needs to take care of their sexual health. That begins with a
conversation with your doctor and around HPV. Knowing what your options are,
where you are with your insurance with the coverage you have and exercising
those at the very minimum is what Dr. Palefsky said, get that digital exam once
a year and if you have access to getting a cytology, get a swab, get it if
you’re getting treated. If you’re in a study, by all means enroll because
that’s how we’re going to get this answer once and for all.
want to make a plea for people to at least consider the Anchor Study. I think
it’s a great study, you’ll be very well taken care of. It could be a great
contribution to the community, people should feel very free to contact me
directly if there’s any questions.
study takes anybody with or without insurance. There’s no cost. You probably
have a better chance to getting monitored and cared in this setting than … We
really don’t have an HPV, like you said, guidelines in this country. I’m
definitely supportive of this study, at the beginning I was not, I thought
everybody should be treated when you’re diagnosed but obviously I have evolved
on that issue due to my own experience of being overly-aggressive on the
really appreciate you joining us. I think, as I said, I’ve been a big fan of
your work, I’ve read almost everything you’ve posted and you print and you
thank you so much also, you do great work for the community. Jeff is one of
those unsung heroes, he goes to every meeting. I don’t even know how he does
it. I used to be that way, I lost steam along the way but Jeff is still going
will be posting a transcript of this doc on the comment section of the YouTube
video, also on PowerUSA.org, which is the website for my non-profit called
Program for Wellness Restoration and we will be doing another Google Hangout in
a month or so and looking at different topics. One of them is concerning people
that want to go back to work after being on disability for many years, since
now we’re living so much longer and people are actually looking at all their
age and financial issues around that.
you so much, Dr. Palefsky, Jeff Taylor, Scott.
you so much and stay tuned for the next Google Hangout for Power.