Friday, April 08, 2016

Life Expectancy Rising in HIV Group Over 50, But Still Lags General Population


Estimated median survival in the HIV group rose from 11.8 years in 1996-1999 to 17.8 years in 2000-2005 and to 22.5 years in 2006-2014. Median survival in general population controls was 30.2 years across all three periods. Mortality rate ratio comparing HIV-positive people with controls was highest among 50- to 55-year-olds (3.8) and declined in each older age group. But in the oldest age group, 75- to 80-year-olds, people with HIV still had a significantly higher death rate than population controls (mortality rate ratio 1.6, 95% confidence interval [CI] 1.0 to 2.6). Mortality did not differ substantially between HIV-positive people diagnosed before or after age 50.
The "well-treated" subset included 517 people with HIV and 3192 age- and gender-matched general-population controls. Estimated median survival from age 50 was 25.6 years in the HIV group (to age 75.6) versus 34.2 years in controls (to age 84.2). Those numbers meant people with HIV but without AIDS or comorbidities had a 70% higher death rate than general-population controls without comorbidities (mortality rate ratio 1.7, 95% CI 1.2 to 2.3).
The researchers concluded that "survival after age 50 has improved markedly in the HIV-population within the [combination ART] era, but is still substantially lower than in the background population," even in "well-treated" HIV-positive people without AIDS or comorbidities.

http://www.thebodypro.com/content/77347/life-expectancy-rising-in-hiv-group-over-50-but-st.html?ic=700102&sp_rid=MTE5OTM3MTAzOTg5S0&sp_mid=8757147

New HIV Drug Has Potential for Weekly or Once-Yearly Dosing




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.

http://www.thebodypro.com/content/77313/new-hiv-drug-has-potential-for-weekly-or-once-year.html?ic=700102&sp_rid=MTE5OTM3MTAzOTg5S0&sp_mid=8757147

Switching HIV+ Patients From Stribld to Genvoya Improved Proteinuria but Not eGFR


CROI 2016 Conference

Abstract Number: 
795

Safety of Tenofovir Alafenamide in Renal Impairment

Author(s): 
Anton Pozniak2, Jose R Arribas3, Samir K. Gupta4, Frank A. Post5, Anchalee Avihingsanon6, Gordon Crofoot7, Kenneth A. Lichtenstein8, Moti Ramgopal9, Ploenchan Chetchotisakd10, Marshall W. Fordyce1
1 Clinical Research, Gilead Sciences Inc, Foster City, CA, United States. 2 Chelsea and Westminster Hospital NHS Foundation Trust, London, United Kingdom. 3 Hospital Universitario La Paz, Madrid, Spain. 4 Indiana University School of Medicine, Indianapolis, IN, United States. 5 King’s College Hospital NHS Foundation Trust, London, United Kingdom. 6 HIV-NAT, Thai Red Cross AIDS Research Center and Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. 7 Crofoot Research, Houston, TX, United States. 8 National Jewish Health, Denver, CO, United States. 9 Midway Research Center, Ft. Pierce, FL, United States. 10 Khon Kaen University, Khon Kaen, Thailand.
Abstract Body: 
Background: Tenofovir (TFV) is renally eliminated, and the prodrug, tenofovir disoproxil fumarate (TDF), has been associated with renal toxicity and reduced bone mineral density (BMD), and must be dose adjusted in patients with estimated glomerular filtration rate (eGFR) < 50mL/min. Tenofovir alafenamide (TAF) is a novel prodrug of TFV that is not renally eliminated and at clinical doses results in 90% lower plasma TFV levels as compared to TDF. The safety and efficacy of a once-daily single tablet regimen of elvitegravir, cobicistat, emtricitabine, and TAF (E/C/F/TAF) was assessed in HIV-1 infected patients with mild to moderate renal impairment.
Methods: Virologically suppressed adults with stable eGFRCG (Cockroft”‘Gault) of 30 to 69 mL/min had their treatment switched from both TDF- and non-TDF-containing regimens to open-label E/C/F/TAF. Week 24 efficacy and safety data are described, including tests of renal function and BMD. Actual GFR (aGFR) was assessed with iohexol clearance in a subset of subjects.
Results: Of 242 subjects enrolled and dosed, mean age was 58 years (range: 24 – 82), 18% Black, 39% hypertension, and 14% diabetes. 65% were taking TDF-containing regimens prior to switch. At baseline, median eGFRC-G was 55.6 mL/min (33% eGFRC-G 30-49 mL/min). 95% of subjects maintained HIV-1 VL <50 24="" at="" baseline="" c="" change="" egfr="" from="" median="" ml="" q3="" snapshot="" span="" style="border: 0px; bottom: -0.25em; font-family: inherit; font-size: 10.5px; font-stretch: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; line-height: 0; margin: 0px; outline: 0px; padding: 0px; position: relative; vertical-align: baseline;" the="" week="">C-G
 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<0 .001="" 0.74="" 1.27="" 2.03="" 24="" 3.83="" all="" and="" baseline="" bmd="" change="" for="" from="" hip="" iqr="" median="" p="" percentage="" respectively.="" spine="" to="" was="" week="">
Conclusions: These 24 week data support the virologic efficacy and renal and bone safety of once daily single-tablet E/C/F/TAF for use in HIV+ patients with mild and moderate renal impairment (eGFR 30 to 69 mL/min). Switch to E/C/F/TAF was associated with no change in aGFR and with reductions in proteinuria.
Session Number: 
P-Q8
Session Title: 
Renal Dysfunction: ART and Biomarkers
Presenting Author: 
Pozniak, Anton
Presenter Institution: 
Chelsea and Westminster Hospital NHS Foundation Trust

HIV Mutates Around Promising Gene Editing Technology (CRISPR-CAS 9)


HIV can defeat efforts to cripple it with CRISPR gene-editing technology, researchers say. And the very act of editing — involving snipping at the virus’s genome — may introduce mutations that help it to resist attack.
At least half a dozen papers over the past three years have explored using the popular CRISPR–Cas9 gene editing technique to combat HIV, but the latest finding, described in a study published on 7 April in Cell Reports1, adds to questions about the feasibility of the approach. However, the researchers involved say that the discovery is a minor setback that does not preclude the idea altogether.

http://www.nature.com/news/hiv-overcomes-crispr-gene-editing-attack-1.19712

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.”

http://www.aidsmap.com/HIV-related-wasting-can-have-long-term-consequences/page/3014398/

Reference

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.




TRANSCRIPT:


Google Hangout : HPV and HIV- With Dr Joel Palefsky and Jeff Taylor

Nelson:                               Hello 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 Hangout.
                                            These hangouts are happening once a month. They are part of our educational efforts to bring the different topics to the community.
                                           This 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.
                                             I've 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.
                                             Dr. 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.
                                            
Dr. Palefsky:                      Sure. 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 about disease.
                                             The 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.
Jeff Taylor:                         Okay I should hang up?
Nelson:                               Well. Jeff. I guess Jeff Taylor. Jeff we can hear you now.
Jeff Taylor:                         Can you?
Nelson:                               Yeah, there you go.
Scott:                                  Yeah. Sorry about that. I didn't mean to interrupt.
Nelson:                               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.
Jeff Taylor:                         Sure. 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.
                                             It's 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.
Nelson:                               Yes, 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.
Dr. Palefsky:                      Sure.
Nelson:                               Go ahead please.
Dr. Palefsky:                      Speaking 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.
                                             Essentially, 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.
                                             The 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.
                                             That 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.
                                             What 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.
                                             The 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.
                                             The 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.
                                             To 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.
                                             Again, 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.
                                             So 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.
                                             The 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.
Nelson:                               Yeah, let's do that. That's a good transition.
Dr. Palefsky:                      Okay. 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.
Nelson:                               Before we move on, when you say HPV types, can you tell us, there's more than one HPV?
Dr. Palefsky:                      Yes. 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 progress cancer.
                                             The 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.
                                             Now 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 Quadrivalent.
                                             For 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 perfectly fine.
Nelson:                               You're telling us it doesn't matter if you're gay, straight, top or bottom, right?
Dr. Palefsky:                      Yeah.
Nelson:                               How do we know if we have those HPV types and whether or not the vaccine, either one of those vaccines will help us?
Dr. Palefsky:                      Great 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.
                                             So 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.
                                             You 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 main thing.
                                             In 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 safe.
                                             The major downside really is to their pocketbook and their finances because it's not a cheap vaccine.
Nelson:                               It requires three right? Three boosting shots.
Dr. Palefsky:                      Yes. 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.
Jeff Taylor:                         What is the cost of the vaccine Dr. Palefsky?
Dr. Palefsky:                      Well 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 more.
Nelson:                               In Houston it costs $250 to $300 every injection
Dr. Palefsky:                      Yes. 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.
                                             There's 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.
                                             So 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.
                                             For 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 about already.
                                             The 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.
                                             All 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.
                                             Now 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.
Nelson:                               No pun intended.
Dr. Palefsky:                      No pun intended. We don't make any jokes. We've never have anything funny to say in this business.
Nelson:                               No. Sorry. Yeah.
Dr. Palefsky:                      Unfortunately 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 cancer.
                                             You 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.
                                             We've 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.
                                             So 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.
                                             Just 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.
                                             It's 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.
                                             So 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 positive people.
                                             The 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.
                                             After 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.
                                             What 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.
                                             We're 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.
                                             The 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.
                                             Taking 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 biopsy.
                                             If 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.
                                             Now 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.
                                             I 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.
Nelson:                               Let 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.
Dr. Palefsky:                      There's 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.
                                             That website I can give you. It's www.iansoc.org
Nelson:                               Yours for UCSF is what, the ANCHOR.
Dr. Palefsky:                      I would good the ANCHOR clinic at UCSF and it will give the website I don't have it memorized actually.
Nelson:                               Okay. 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.
Dr. Palefsky:                      Sure.
Nelson:                               Jeff 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.
Jeff Taylor:                         Thanks 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.
Jeff Taylor:                         Okay, 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.
                                             I 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 ...
Nelson:                               I've 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.
                                             In 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.
                                             Jeff 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.
Jeff Taylor:                         Yeah. 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.
                                             Actually 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 get surgery.
Nelson:                               Thank 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.
                                             I 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.
Dr. Palefsky:                      Okay. 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.
Nelson:                               Oh.
Dr. Palefsky:                      In 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.
                                             Our 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.
                                             If 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.
Nelson:                               How about CD4's? Do they matter?
Dr. Palefsky:                      They 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.
Nelson:                               So it doesn't matter what t-cells you have, you should get checked too, okay.
Dr. Palefsky:                      I 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 ART.
Nelson:                               Good. Just moving on to the study itself, then.
Dr. Palefsky:                      Sure.
Nelson:                               Why don't we go for it.
Dr. Palefsky:                      So 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."
                                             The 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.
                                             It 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 people.
                                             Just 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.
Nelson:                               Who are those? Who are them?
Dr. Palefsky:                      Who are them? [crosstalk 00:51:08]
Nelson:                               Monks, not even monks.
Dr. Palefsky:                      There 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.
                                             Firstly, 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.
                                             Basically, 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.
                                             We 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."
                                             It's fewer than 1 in I think 200, will develop cancer. So that's small, it's not zero but it's small.
Nelson:                               How frequently are you going to monitor?
Dr. Palefsky:                      The 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.
                                             Of 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.
                                             The 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 about.
Nelson:                               How long is the study and how many people and how many sites?
Dr. Palefsky:                      It's 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.
                                             The 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.
Nelson:                               That's good.
Dr. Palefsky:                      Thank 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.
                                             We 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."
                                             That's what's going to happen.
                                             The 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.
                                             There 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."
                                             We 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.
Nelson:                               Can they website to find out more information about the study?
Dr. Palefsky:                      It's www.anchor.org. I think that's right. Might be anchordmc.org.
Nelson:                               Anchor is one word that is really hard to buy as a website. It's probably going to be ...
Jeff Taylor:                         Anchorstudy.org.
Dr. Palefsky:                      Anchorstudy.org. Okay.
Nelson:                               Okay. Anchorstudy.org. Okay and that's all the inclusion, exclusion criteria, how to join, where the different places are, right? Are listed there?
Dr. Palefsky:                      We 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.
Nelson:                               Yeah. 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.
Dr. Palefsky:                      Right. 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.
Nelson:                               In the South?
Dr. Palefsky:                      Then 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.
Nelson:                               Palm Springs?
Dr. Palefsky:                      Well we don't know yet about Palm Springs.
Nelson:                               Fort Lauderdale, Miami?
Dr. Palefsky:                      We are hoping to open a site in Miami. Possibly a site in Houston. Possibly a site in Chapel Hill and what am I missing?
Nelson:                               You'll be spreading them I'm sure, even more.
Dr. Palefsky:                      Yeah.
Nelson:                               It is enrolling right now, right?
Dr. Palefsky:                      The 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.
Nelson:                               Do they need to bring records from their doctor or do you guys take care of that?
Dr. Palefsky:                      We'll 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.
Nelson:                               One more question on related to the study because it really struck me as odd. Why did you guys decide on the age of 35?
Dr. Palefsky:                      Okay. 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.
                                             We 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.
                                             Does that make sense?
Nelson:                               Yeah. Yeah. Of course. For those who are under 26 and are HIV positive and high risk they can talk to their doctor about vaccinations?
Dr. Palefsky:                      I 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 vaccinated.
Nelson:                               That's 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.
                                             One 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.
Dr. Palefsky:                      Sure.
Nelson:                               It 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.
Dr. Palefsky:                      Sure. 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.
                                             Then 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.
Nelson:                               Yes.
                                             Yeah 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
                                             Anyways, 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?
Jeff Taylor:                         Sure. 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.
Dr. Palefsky:                      I 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.
Jeff Taylor:                         This 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 situation.
Nelson:                               I 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 publish.
                                             Jeff, 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 on strong.
                                            We 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.
                                             Thank you so much, Dr. Palefsky, Jeff Taylor, Scott.
Dr. Palefsky:                      My Pleasure.

Nelson:                               Thank you so much and stay tuned for the next Google Hangout for Power.



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