Thirtieth Meeting

June 20, 2006

The above-entitled matter convened at 9:00 a.m. in Room 800 of the Hubert Humphrey Building, 200 Independence Avenue, S.W., Washington, D.C., Louis Sullivan, M.D., Co-Chair, presiding.

Council Members Present:

Louis Sullivan, M.D., Co-Chair Troy Benavidez, Member Robert Bollinger, M.D., M.P.H., Member Jacqueline S. Clements, B.S., Member Edward Green, Ph.D., Member Alan Holmer, B.A., J.D., Member Jane Hu, Ph.D., Member Franklyn Judson, M.D., M.P.H., Member Sandra McDonald, Member Joe McIlhaney, M.D., Member Robert Redfield, M.D., Member David Reznik, D.D.S., Member M. Monica Sweeney, M.D., M.P.H., Member Ram Yogev, M.D., Member

PACHA Staff Present:

Joseph Grogan, Esq., Executive Director
Dana Ceaser, Program Assistant

Presenters:

Michael Saag, M.D., Professor of Medicine, Director, University of Alabama at Birmingham

Myron S. Cohen, M.D., J. Herbert Bate Professor of Medicine, Microbiology, and Immunology and Epidemiology Director, UNC Center for Infectious Diseases, UNC Chapel Hill

Contents

• Welcome Remarks
  • Co-chair Sullivan
• Treatment and Care
  • Member Reznik
• Healthcare Cost Study
  • Dr. Saag
• Seroconversion/Infectivity Data
  • Dr. Cohen
  • Public Comments
• Departing Member Recognition
  • Exec. Director Grogan
• Council Reconvenes for Motions and Working

Proceedings

(9:03 a.m.)

CO-CHAIR SULLIVAN: Let's try and get started because we would like to adhere to our time schedule for the meeting today. One thing I failed to mention yesterday, but I'm sure all of the Council members will agree with me. I congratulated Joe Grogan and his staff for the book that was put together for our meeting.

(Applause.)

EXEC. DIRECTOR GROGAN: Thank you but I wish B- I can't take any credit for that. It was really Dana who put this all together and she did a fantastic job.

(Applause.)

CO-CHAIR SULLIVAN: Certainly excellent, very good papers and good biographical sketches. So thank you very much for this very fitting for the 25th year of this epidemic. We also had some very good discussions and presentations yesterday and I'm sure that will continue through to today. Our session this morning will be presided over by the Chair of our Treatment and Care Committee, Dr. Reznik. So, David, we'll let you go forth.

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MEMBER REZNIK: Good morning, everyone. We have some people that are awake. Today we're going to cover a couple of very important issues and our first speaker, which is actually an honor for me to introduce him, I think it's our first speaker, let me make sure, is Michael Saag. Michael Saag graduated from the University of Louisville with his medical degree and then did a residency in infectious disease in molecular virology at UAB or University of Alabama at Birmingham.

During his fellowship training, actually while a fellow, Dr. Saag conceived a concept of a comprehensive HIV outpatient clinic dedicated to the provision of comprehensive care in conjunction with the conduct of high quality clinical trials, basic science and clinical outcomes research. This is as a fellow. So that is really very unusual. At least in today's world, it's a little bit unusual. Since he established the clinic, Dr. Saag has participated in studies of antiretroviral therapy as well as novel treatments for opportunistic infections.

Some of his articles include the description of the first use of viral load in clinical practice, the first description of rapid dynamics of viral replication, the first guidelines for the use of viral load in the practice, the first proof of concept of fusion inhibitors as a therapeutic option and also making available many antiretrovirals that were only available through research trials.

In the early days of the epidemic, many of our patients in Atlanta actually took the trip to Birmingham to see Dr. Saag to get access to care. And I believe it was last year one of our community group had a survival project to honor Dr. Saag for his commitment not just to people in Birmingham but to the people in Atlanta and around the country.

As many of you know, my partner was sick earlier, all of last year, and when things came down to a crisis, we have a wonderful medical director at Program, Dr. Jeff Linnox. I called up Dr. Saag because things were getting to the point where I needed to contact the brains and people that also have the compassion and the two doctors got together and I can happily say that my partner is doing much better. Truly a great person, dedicated to dealing with this disease and facing the problems as they are emerging, it is my privilege and honor to introduce Michael Saag.

(Applause.)

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DR. SAAG: Thank you very much. I'm going to speak from here if that's okay and I'm going to take only about 20 to 25 minutes and leave time for discussion because I know that a lot of you have ideas as well. But the thesis of what I want to talk about is care, HIV care delivery and while you may think that this is an exaggeration that in my opinion is an emerging crisis in care, there really is, and I think by the end of my remarks, you'll hopefully see what I'm trying to say.

So we'll start with our clinic in Birmingham, and what you're looking at is a Kaplan Myer survival plot and to sort of walk you through this, this is eight years worth of data. These are data from HAART Era and just to translate this for you, if someone shows up with a CD4 count greater 200, the majority of them, this is the top two bars, are alive eight years later. If they show up a CD4 count less than 200 at initial presentation, don't start the HAART regimen until after a CD4 count of 200 and if they're between 50 and 199, that's their line, and if they're less than 50, that's where they go. So that up to almost half of the patients who show up with a CD4 count less than 50 in the HAART ERA are dead eight years later still today.

The next slide shows you, in our clinic, the median CD4 count of someone showing up for care. It speaks for itself. This is in today's world with all that we know about HIV, all the messages that are out, everything that you've been dealing with personally at whatever level you're at, the median CD4 count of patients. Look at 2003. A hundred was the median CD4 count of someone showing up in our clinic referred for care. What it means is that people who are infected with HIV at least in my part of the world, and I think it's a lot of the United States, are infected and don't know it and they don't seek care until they get sick.

So the take-home point is kind of obvious. Mortality is much higher when patients diagnosed late. The majority of newly diagnosed patients are diagnosed late. The exception to this are pregnant women. The median CD4 count of a pregnant woman seen in our clinic is 400. Why is that? We have universal opt-out testing for women. So? Universal opt-out testing is needed.

Now 20 years ago, I would not have been saying that. Fifteen years ago, I would not. I've been on the other side. Why? Because 15 or 20 years ago, all we had to offer somebody who was diagnosed HIV positive, all we had to offer them, was discrimination.

Now there is still discrimination, unfortunately, but at least we have therapy and we have a way to keep people alive and in my opinion, if you can get somebody into to care, especially early, and you treat them, it's like diabetes. Yes, there are complications of treatment. Yes, there are complications of disease, but the majority of people will live for decades, and I'm talking into the 70s, 80s and 90s. So that it's a public health point that we should testing, or at least offering testing, with appropriate counseling to everyone and if they choose not to be tested, that's their decision. But I would say anyone who has ever been sexually active in their life should be tested at least once.

Now, that's the background. Let me segue into another study out of our clinic, and this is a cost study that was published a couple months ago in Clinical infectious Diseases. What we wanted to do was to determine the annual health care expenditures for HIV stratified by CD4 count.

Now this has been modeled a lot, but this is actual data from actual utilization of our clinic. We described the cost components of health care, medications, labs, hospital, etc. to analyze the effect of the changing CD4 count on expenditures. We took our database out of our clinic that we captured data since 1988 on every patient and this was looking at mainly the year 2001 and established care January 1994.

In 1999, we had a pretty big change where we could start incorporating health care utilization which would include all these metrics. So once we started capturing that, then we could assign costs based on utilization.

So for inclusion criteria for this study, they had to be receiving their primary care at UAB. We have a lot of patients who are referred in from Atlanta or other places. But the only ones we included in the study were those actually came exclusively to UAB for their care. The baseline CD4 count had to be available and follow-up of at least once and for hospitalization for that one year period.

We took the actual utilization and assumed that every patient had Medicare insurance to create a level playing field. So everyone had Medicare and reimbursements were based on Medicare rates in Alabama, complete billing for all health care use, and that we collected 100 percent of whatever was charged. For medications, we simply used average wholesale price. So we had every medication with a start and stop date and we could assign this.

This is the demographics. This has changed actually in our clinic since 2001-2002. The age is a little bit higher now, fortunately. It's about 42. At that time, there were about 40 percent blacks. Now it's about 50 percent. Men who have sex with men is now, in our clinic, about 48 or 49 percent, and most of the patients now of the last 300 patients referred to our clinic in the last year, 50 percent of them had no health insurance.

So these are the data, and what I'd like to do is, I'm going to walk you through this. Let's start with this first column and what you'll notice is that when the CD4 count is high, annual costs are low and when a CD4 count is low, annual costs are high. And it's pretty remarkable how almost linear that is, so that not only is somebody showing up late at higher risk of dying. They also cost more money and the overall average cost was about $18,600 per year.

If we look at the reason why the costs are higher late versus early, it's mostly in non antiretroviral medications and somewhat in hospitalization, but hospitalization which everybody focuses on really is only a small component of the overall cost of care even among those with less than 50 copies. If you take them as a group, it's only about eight or nine percent of the total health care expenditures. The take-home point here is that 75 percent of cost no matter how you slice it, no matter which CD4 count strata you're in, is medications. Seventy-five percent of cost is medications in any CD4 count strata you look at.

And then finally, look at this. If I charged accurately for a Level 3/Level 4 visit, everyone had insurance and I collected 100 percent, on average I would only collect for our clinic $360 per patient per year. For a 1,000 patient clinic, that's $360,000 a year to do everything, pay the doctors, nurses, reception, rent, utilities.

This is a statement about our health care delivery system and in HIV care in particular, you can't make money. Why? Because the $359 per patient per year is assuming everyone has insurance and our collection rate is 100 percent. About 40 percent of our patients have no insurance. Our collection rate is about 40 percent. So in that year, our actual reimbursement from third parties, not counting Ryan White or anything else, was about $130,000 for that year total to our clinic.

The bottom line is you can't make it in clinical practice in HIV. And if you look around the country, a lot of the so-called boutique practices in New York, Los Angeles, San Francisco, they're dying. They aren't, those practices are going away and almost the majority, clearly the majority of patients who are seeking HIV care today are doing so through publicly-funded clinics around the country.

Let's look at this a little differently. So there is some good news in here. We simply asked the question, if you took at the six-month point in the study, you took the original CD4 strata they were in and asked the question, at six months later were they in the same strata or did they improve or did they get worse, and that's what this graph shows. If we just focus on the this 50 to 199 group CD4, they started in this group. If they stayed the same, their annual costs were about $24,000 per patient per year. If they dropped to the less than 50 group, their costs jumped to here. But if their CD4 count went up to that group in the course of six months, their costs were lower and this was statistically different. That dropped about $6,000 less.

How do you get CD4 counts to up? Well, you treat them with antiretroviral therapy and this is just another way of showing that ARV therapy is cost effective. Good news.

But look at where the cost savings were. Most people would guess it was in hospitalization, and indeed, there's a big difference here. The antiretroviral therapy medicines costs is about the same and you might predict that, because you're only going to give so many drugs and that's what they cost. But most of the difference in cost was in the non antiretroviral medications. People got sick and they required foscarnet or cidofovir or whatever, chemotherapy, and that's where the majority of the costs are and again to reiterate my point, the majority of the cost no matter how you slice it is in medications.

Look at this. This is my whine. This is us over here trying to make it, trying to get through day to day. So the conclusions are antiretroviral therapy is cost effective. Medications are the most expensive component and physician costs account for less than two percent of expenditures, even in the most optimal conditions and it's certainly much less than that.

So before I go further, I'll just ask the question. If you were a young physician coming up through training, would you choose to go into HIV medicine or would you choose to go into dermatology or would you choose to go into radiology or would you choose to go into some other specialty that pays a little more? Who in their right mind would choose this specialty? Which gets to the next question, where is the next wave of doctors going to come from who take care of HIV patients? Where is that going to be? So that is one of the questions I want to have a discussion about with you guys when I get through. So that's Point 1.

Another point is when we think about Ryan White, the original authorization, think about that time versus now. In 1991 when that authorization legislation was first put through, people were dying of AIDS everywhere. There were no medicines to speak of, a few, but none worked very long. Patients were dying. So what did we have to do? We had to help people learn to live with disability and we had to help them die with dignity. And the Ryan White Act helped us do that.

Things are very different now. Patients, fortunately, aren't dying to the same degree. The Disability, we have people coming off of Disability and going back to work. The crisis right now as I see it isn't in providing even case management or social services like it was when this was first authorized. The crisis is in providing care, in providing health care.

So your group recently said this, "Every American who needs HIV treatment and care should have access to it." Couldn't agree with you more. People who are HIV positive need essential medications. Absolutely true. Without the drugs providing care is difficult to impossible. True. True. True. But is that enough?

The policy implications or the provision of antiretroviral care and other essential medications means that we should be funding ADAP to a fuller extent. I've lived in a state that since the beginning had a waiting list, had a waiting list for medicines, an embarrassment to our state. But you know what? There hasn't been a single patient who has gone without medicines out of my clinic ever, not once. Not one time. Why? Because our Social Service work their tails off to apply for compassionate use programs when people don't have medicines and the pharmaceutical companies, fortunately, would provide those medicines on appeal. So there was a stop gap. Where is the stop gap for care if there is no physician, if there is no clinic?

The reality check. In our clinic, that's why I showed you data from our clinic, so I could keep it simple. Our operating budget is $2.1 million a year for about 1,400 active patients. Third party payment, and this is generous, is $250,000 a year for care and another $250,000 a year for infusion therapy for those who are getting chemo and other things. Our Title III funding is $508,000 a year. That's been the same for the last seven years despite a 60 percent increase in our clinic patient load and last February I was told we were getting a five percent cut despite funding for seven years, despite clear documentation of increase in burden. Now that cut was changed to 2.5 percent cut in March or April, but it's still a cut.

It's hard to swallow that. It's hard to tell my providers, those social workers and other who are working their tails off every day, that I can't hire another person. I don't have another FTE to absorb the volume and what they're dealing with now as a side bar is a tragedy with Medicare Part D. Why? All the patients in our state who are Medicaid/Medicare co-insured in December got their medicine through Medicaid. January 1, they got their medicines through Medicare Part D.

Here is what happens. Let's say they have eight prescriptions. They go to the pharmacy. They've enrolled in Medicare Part D. The pharmacy tells them, well, we can fill these five but three of these require prior authorization. They take their prescriptions back to us. We get on the phone. First, we have to figure out what plan they're in. It could be one of 14. Then they call the 1-800 number, get put on hold for 15 minutes and they're told, you dialed the wrong number. Call another one. Get put on hold another 15 minutes.

Then they say we're going to fax you a form. You fill out the form. Somebody has to. Fill out the form and that's a request for review. That form has to be signed by a physician. So the nurse has to go find the doctor and get him to sign that and fax it back in. They have 72 hours to respond. They send us another fax form which is actually the review. They have to go to the chart. They have to find out their insurance status. They have to find out all this information, fill out another form, get the physician to sign it, send it back in. Seventy-two hours later, almost always it gets approved.

That process takes one of my health care providers 30 minutes to an hour per prescription per patient. I'm not exaggerating, and I have providers right now who are on the verge of quitting. If they quit, who do I replace them with? It is really devastating what's going on in our clinics right now and I see other doctors around the room who are listening to this nodding yes. So I'm not alone. This is what we're going through.

So the key points, mortality is higher when the patients are diagnosed late. I've told you that. The majority of people show up late. Many patients don't know it. Universal opt-out testing. But with more universal testing, I'm predicting, at least in my neck of the woods a 25 to 50 percent increase in patient volume. That's good that we're finding people who need care, hopefully earlier. But here is the question; who is going to take care of these folks? So with the new Ryan White Reauthorization, we're getting rid of waiting lists and I"m afraid we're going to replace them with waiting lines. Where are people going to get care? Where is it going to come from? Who is going to do it?

We're about maxed out and I'll show you this quote. This is from this month, Laurie Dill. Trained at UAB, running something called Montgomery AIDS Outreach, a Title III recipient. Let's just read it together. Medical Director, this guy, her co-medical director, Larry Williams, resigned from MAO on 6/7. "I, Laurie, will be the acting medical director while we recruit and hire a new medical director. We are currently actively looking to fill positions, a full-time medical director and a part-time physician to see patients mainly in our rural satellite clinics. As you know, MAO is a Ryan White funded agency. We currently have myself and two practitioners to provide staff. We have three clinics in Montgomery and Dothan and hold once or twice a month clinics in six other satellite clinics. We follow 1,000 patients in a 23-county area in south central Alabama. Please contact me for other information."

What's her chance of finding another doc or doc and a half? This is happening today and the thing that concerns me is that this is probably news to a lot of you and it's because a lot of us in the trenches are so consumed with day-to-day function we don't have time to come to D.C. and talk. But a lot of us have changed that, at least I have, in the last several months.

So the policy implications. Funding of ADAPs for sure, but we do need a dramatic increase in funding to increase clinical capacity. Title III in my opinion from what I've observed has been largely ignored in the reauthorization. ADAP has been front and center. Every single thing I see coming out of D.C., ADAP, ADAP. Great.

What does ADAP do? It provides medicines for patients. How? By paying for them. But nobody went without before. So the beneficiaries are predominantly the pharmaceutical industry and the patients. Yes, they both will benefit. I'm not saying that's bad or evil, but I'm saying it can't just be ADAP. It has to be a more comprehensive look at care.

So we need to do this by increasing Title III funding and provide incentives for younger docs to go into practice. We need to do something loan repayment. The HIVMA which I'm on the board of directors has put forward a proposal just to simply put in this some loan repayment for doctors who commit to HIV care. I don't know where the young doctors are going to come from.

We need creative solutions to encourage more doctors in advance to choose the skills to treat HIV, tuition reimbursements, insure adequate reimbursements for care. As we expand our clinical capacity to treat HIV positive Americans, we must not forget quality. HIVMA called for the Care Act for a portion, this was actually cut, from the bicameral, bipartisan legislation so far.

Seventy-five percent of care as we said are on core medical services. Good. That's good. If it were up to me, I'd say 95 percent, but I'll take 75 percent. That's good. We have to put care first and require that ADAP programs cover a minimum of the formula. Okay. I like that. But there are no provisions to promote qualified careers, no significant increase here and no training incentives.

So this is what you guys said. We've already gone over this, but I would change that. "Provision of medication" should be "provision of care" and without qualified HIV care clinics, the drugs mean nothing. Nothing. The drugs don't mean anything unless somebody is there to monitor them and those of you who practice HIV medicine know that it is the most difficult type of practice you can possibly deal with.

A cardiologist gets paid $80 roughly for interpreting an EKG. Most docs when they finish medical school can do that mostly and in fact, the computer does it for you most of the time. Right? $80. What do I get for interpreting a complex resistance profile? Nothing. What do I get for filling out prior authorizations for an hour? Nothing. What do I get for fielding phone calls from distraught patients who are having side effects of the medicines? Nothing. What do I get if I charge a Level 4 visit and get audited and only document a Level 3? Arrested for fraud.

This is what we're up against. So I'll turn it over to you and maybe we can think together about what types of solutions we can have and I'm sorry to bring you such a troubling message, but this is what's happening and this is the truth.

MEMBER REZNIK: Thank you, Dr. Saag. We'll take questions, but I do want to since you quoted from our Presidential Advisory Council blue book which I happen to keep with me at all times, one of our recommendations actually was creative solutions must be found to encourage more doctors, PAs, advanced nurse practitioners to choose to develop the skills necessary to treat HIV and included in that recommendation was to issue reimbursement for health care workers who choose HIV care in medically under-served areas, encouraging recognition of HIV care as a medical specialty, provide incentives for more nurses, physician assistants, nurse practitioners and physicians to be certified through their appropriate associations, ensure adequate reimbursement for HIV care and promote programs to increase the diversity of health professionals trained in HIV care.

Now that may not have shown up in Reauthorization, but as long as I'm on the Council and I think I have a few months left we're going to definitely push that concept. I mean I think you make some great points, but I'm going to get off that little soapbox and see who has questions since I took over yesterday. Dr. Sweeney.

MEMBER SWEENEY: Thank you very much for that sobering message. I'm an internist practicing in Bedford Stuyvesant, Brooklyn and I work in a community health center and one of the strategies that some health centers are taking and I'm hoping to do in the future, all of the internists who work or are hired now have to agree to be trained to take care of HIV patients in one of our community health centers, so that eight people who are adult medicine docs, not just docs, they are mid levels as well, all have to agree if they want to work in this particular center that I'm referring to to be trained in HIV.

Now that is a public institution in the truest sense. We have to take all comers regardless of their ability to pay and it's one of the ways that we integrate primary care and specialty care of HIV not only so that we have greater person power, but so that there is not the discrimination of having an HIV clinic and so if you go to that side of the room, somebody knows of the building, somebody knows. I was just wondering what you would think of that as a model to try and have more primary care physicians trained to be HIV specialists as part of their primary training.

DR. SAAG: I like the idea of training people. My experience has been that if people don't want to be there they'll find ways to circumvent. So unless you're self-selecting for people who want to be there and do HIV care, there could be a problem in universalizing that as a policy because people who don't want to go someplace won't go. They'll find a way to B- They'll vote with their feet. So training people who want to be there is good, but I think the other issue is incentivizing them. Right?

I'm sure your clinic is publicly funded in New York and Brooklyn and everywhere there is much more money typically than in some other parts of the country. So that's good. So I assume your clinic is not running in the red. Right? So at least, you can pay the folks who are there and that's good. I think training is good and that's a nice idea.

MEMBER SWEENEY: I just want to follow it with you talked about the difficulty in treating patients with HIV because of the complexity of medications. But you know in many other specialties, internists and primary care physicians do much of the work-up, diagnosis and beginning treatment and you refer to a specialist when it becomes too complicated or to give you a program to follow and then they are followed concurrently with a specialist and a primary care physician. Why can't that be a model for treating patients with HIV?

DR. SAAG: It works on one critical assumption that I'm not sure is true and that is that the competency of the primary provider is such that they understand the nuances of HIV care. It's not a cookbook formula even for starting therapy. I had a referral from a primary doc who thought they were doing a great job three weeks ago who diagnosed somebody in Pell City, Alabama, sent them to me on Combivir, monotherapy alone.

So I mean harm can be done. You have to assure that whoever's doing it is well trained, not just trained. And so there's a lot of harm that can be done. It's like somebody trying to give chemotherapy when they're not an oncologist and you're right. When you have to incorporate more people, absolutely, but the training has to be there too.

MEMBER REZNIK: Alan Holmer.

MEMBER HOLMER: Thanks for the powerful presentation. What portion of your patients are eligible for Medicare and in searching for solutions, is this a conversation that if Mark McClellan, the head of the Center for Medicare and Medicaid Services, who is an M.D. and a spectacular individual, if he were here, are there solutions that we might be able to talk through with him? But first, what portion of your patients are eligible for Medicare?

DR. SAAG: Probably less than 20 percent and the reason is they have to be disabled for two years, etc. And even in our state, Medicaid is ridiculously hard to get. You have to be disabled earning less than $510 a month. And so most people who have worked and they get their disability check, it's over that $510. So the only person who are really going on Medicaid are people who are poor and have never worked or not worked much. It's hard in Alabama, but that Medicare/Medicaid is only a small portion. The majority of our folks, either they have private insurance or they are totally uninsured.

MEMBER HOLMER: Okay. And what portion would be totally uninsured would you guess?

DR. SAAG: About 30 to 40 percent and that's where the Ryan White CARE Act comes in.

MEMBER SWEENEY: Right.

MEMBER REZNIK: I do want to make a suggestion and maybe, Dana, if we could get copies, enough copies of this available for the members because I would like you to look it over as possibly coming up with a motion this afternoon based on our recommendation that we had that we actually wrote last year. Next on the list is our Southern belle, Jackie Clements.

MEMBER CLEMENTS: Well, thank you, kind sir. Dr. Saag, I have more of a comment than a question. I worked with a Title III clinic that is experiencing just what you said. We have about 300 patients, two PAs that see them, one position we have had to replace three times in the last four years simply because it's a lot of work working with HIV patients and there are other places that they can go and get more of a reward other than that heart-felt thing.

The problem with it also is that it is very harmful to the patients to have to go through that many providers in so short a time. There is a connection that you make with your provider and they question the stability of the clinic. They question how well their care is given and how much people care about them. So our consumers are really going through a hard time having to go through so many providers in such a short period of time

DR. SAAG: Has your patient volume increased over the last five years?

MEMBER CLEMENTS: Yes.

DR. SAAG: And has your funding from Ryan White increased?

MEMBER CLEMENTS: No.

MEMBER REZNIK: Dr. Redfield.

MEMBER REDFIELD: Mike, I want to thank you. I mean I think you brought a number of points to the table which I think unfortunately are more universal than people want to acknowledge and I think you're an extremely articulate spokesperson to bring to the forefront. Even in the State of Maryland which is regulated, our inpatient cost gets compensated by some mechanism I don't quite totally understand but I know that the hospital is not that upset about uninsured patients being hospitalized, although that obviously they're not really enthusiastic about them being not hospitalized which I think is probably the wrong incentive.

I don't think any of us can make a clinical program function based on the revenues that we can generate. So this is complicated both for private practice but it's also complicated in the academic setting where you have clinical individuals that have to basically cover their salaries based on their clinical activity.

So I agree with your term. I don't like to overuse the word "crisis" but I think that there's been a lack of attention to health care delivery systems in general and there's clearly a lack of attention to how to stimulate and incentivize in effective way young people to go into AIDS medicine.

We've been trying to recruit African-American physicians now in our program proactively for about the last seven or eight years. We've been successful with several African physicians, one African-American physician. Next year, hopefully we'll have an outstanding young fellow who is African-American.

But as I've talked to many of the young physicians who wants to go into AIDS medicine when they have $100,000, $150,000 loan debt and they are looking at the fact that the only way I can pay them is if they can bring in the clinical revenue if they want to be a clinical person. The reality is like you, we have 40 percent uninsured rate. We have probably a 26 percent reimbursement rate and like you, we've had 40 percent increase in clinic visits last year and no increase in Ryan White funding, actually a cut and actually worse than that, a cut from the hospital from the ambulatory care support.

So I think you've hit something that's so universal. It may be less seen in some of the northern or high volume Ryan White or high financed Ryan White at this point, but it's going to be seen and I think it's something that needs to be really thought through. I think it's unreasonable to expect young physicians to go into a practice where they don't believe that they can be compensated to the point that they can pay back their loans and raise a family.

You and I went into it because we finished our fellowships. We were fellows. Everything else was full. It was a new thing. It was exciting. But I think you've hit it and I think when we get our nation, you and I may have disagreed about the advantage of early diagnosis before. I've always been an advocate of it because at least people would be denied the discrimination of unknowingly infecting someone who is special to them and getting optimal care based on diagnosis.

But clearly today, there's no doubt about it that diagnosis is key and we're about to see probably a 25 to 35 percent increase in people needing care. So I think much more aggressive creativity and it's not all the Federal Government. I think medical groups need to be accomplished.

We talked yesterday about Title III because I'm of a view, you know, I have 42 Ryan White grants in the state of Maryland and each one has to be reported monthly. So I'm writing two reports a day on average. I'm not sure that's the best utilization of our people to be writing monthly Ryan White reports for 42 different grants. We unfortunately don't have a Title III grant which I think is the most comprehensive way to provide care and treatment.

So I think there's going to be both an increased need for support probably from multiple systems including the Federal Government but incentivizing young people to go into AIDS medicine in particular and for incentivizing young people in the south to go into AIDS medicine which is even another area that's even more complicated.

I think it's critical and I just want to thank you. I've read what you've written and obviously published. I read your letter and your memorandum. I think it's well thought through, it's fundamental and I think actually does require much more insightful urgent action. I think getting someone who is knowledgeable about health care economics in our nation to really sit down and think about this like McClellan and others, this is a serious issue and most of us are patching together care right now and I think patches are going to break. I mean people can only work so long and not be compensated for what they do.

DR. SAAG: Sorry to interrupt, but there is one thing that I've thought about a lot and that is the sort of safety net that our country relies on to capture people when they fall into the cracks. The threads of that are made up solely of health care providers who give a damn. If they stop caring, there is no safety net.

They're the ones, they're social workers, our docs. When a patient comes back and says, "I have this prescription that was denied because I need prior authorization," if we just said, "Sorry," that's it. The system assumes that health care providers give a damn and if they stop giving a damn, God help us.

MEMBER REZNIK: Dr. Saag, before I take another question, you did an interview with NPR recently and you were asked a question about burnout. When I listened to it, you paused and I told Mike this on the way over here during that pause I came up with ten different possible ways that I would answer the question. Because one of the issues that we're facing is that a lot of providers have been doing this for years. You've wanted the epidemic change and always wanted to know what was behind your pause and what do you think about our existing providers who have all of these forms to fill out who aren't getting reimbursed who now have to learn basically molecular virology in order to figure out proper treatments for patients? How do you think that impact is B-

DR. SAAG: Real quickly, I mean for those of you B- Michelle Norris has invited me to the NPR studios just down the street and it was a really nice interview and she surprised me with the question actually. She said B- Oh, I was talking about provider burnout. I was referring to a lot of the health care providers in our clinic who I'm worried are going to leave and I can't replace and she turned a question on me and she said, "Well, are you burning out?" And I went "Whoa."

Then I thought to myself "Am I?" And I really did have to think and the answer is no. But the fact that I had to stop and think says something, doesn't it? And like you and I were talking, maybe we're just getting tired. I mean this is fatiguing to fight this fight every day. But no, I'm not burned out yet.

MEMBER REZNIK: Me neither. Next is Dr. Judson.

MEMBER JUDSON: I think the realities of this are just staggering and gripping. I don't want to drag on but I was in Colorado involved with the very first cases and at one point our public clinic within our public hospital system, Denver Health and Hospitals, had seen or consulted on 50 percent of the AIDS patients in the state up until about 1992 or `93. I think the remarkable thing is the quality of the people who were drawn into this struggle from the very beginning and that they have stayed this long.

You are appropriately pessimistic. I guess looking back it was a remarkable effort and every year, I would ask the people who directed, we had directing our clinic when I was Director of Public Health and head of Infectious Diseases there, is there anybody who we have not been able to provide the best treatment that we know over the past year and whether there were waiting lists or whatever else the challenges, most of these physicians could look back and say no, one way or another we haven't turned anybody away. We haven't denied them treatment we thought was important.

But we're clearly at the end of that. Something is going to break. We're still getting interest in some fellows, but I agree with you. That's just B the economic model isn't there to allow it to continue. With Medicaid disproportionate share, we've been able to hold up a health and hospital system where 44 percent of our patients don't pay, $220 million a year of unsponsored care. We're still in the black. We have been since we became a state authority, remarkable achievement, but it's just there`s going to be an end to that at some point.

I think the other side of it though is that we're not the only ones who are beginning to potentially burnout or age out. I think the public appropriately, the taxpaying public, is beginning to look at AIDS like everybody out there either does know or should know what they need to know to prevent HIV infection and should our whole moral effort be based on how do we marshal the resources to continue to try to treat our way out of this epidemic, if we're not able to begin to show, I think, get off of this 40,000 new cases a year or accepting that status quo and proceed towards eventual elimination which I believe we have the means to do, I think the public support for things like Ryan White is going to wane. It's going to even get worse.

Lots of times people are saying that one out of eight woman will be subject to breast cancer and we're spending $3 to $4 billion a year or so on breast cancer which isn't preventable at this point by known means and we're spending $20 billion a year total, approaching $20 billion for HIV/AIDS. So I think in a resource constrained society, that's going to balance out.

So it brings us back to the purpose of PACHA and I think for many of us to get back into making absolutely certain that all of the incentives not to get HIV infection are out there and all the disincentives to get HIV infection are out there and to begin to try to get back on track to the reduction in incidents that we saw for a period of ten years where we went from 170,000 or 180,000 cases a year at the peak down to the 40,000 or so. We're just not going to make it with treatment under economic models, medical models, anything else.

DR. SAAG: One question that I think remains to be answered and Dr. Cohen can address this maybe in his remarks is how much does treatment lead to prevention of transmission and my guess is it's a pretty significant impact, but we need to prove that.

MEMBER JUDSON: I think it's a significant impact but the estimates are that 50 to 60 percent of new cases are still coming from the 25 percent who are undetected and probably highly as we know disproportionally from the relatively new, highly infectious cases in the concurrent partners. It isn't possible I think to continue to maintain multiple concurrent partners during undetected early infection. That's the pipeline.

MEMBER REZNIK: Thank you, Dr. Judson. Dr. McIlhaney.

MEMBER McILHANEY: In the meantime, first I agree with you, Frank, about the exhaustion of the taxpayer, but in the meantime, it's obviously just going to cost money in one way or another to solve that personnel problem.

The average debt I think for physicians coming out of medical school ranges about $75,000. Some of you may know more specifically than I do, but I think that's about what the kids are coming out of school with now.

CO-CHAIR SULLIVAN: I think it's over $100,000.

MEMBER McILHANEY: Is it over $100,000 now?

MEMBER CLEMENTS: Yes.

MEMBER McILHANEY: Okay. I thought I might be a little bit behind and so you know as compassionate as the young people may be finishing up medical school the reality is that they have that debt weighing down on them. There's a model that I'm familiar with and it has to do with Christian Missions. As I understand in Africa, way over 50 percent of medical care there is provided by Christian missionaries and yet the number of young physicians who are willing to go do that was decreasing because of this debt thing and a friend of mine started an organization that started raising funds to pay off the debt for these kids when they finished medical school so they would be free to go on over and start mission work.

It seems to me that might be a model to be considered that we could pay the debt for young people that are willing to go into HIV work, provide them their residency funds and then require that they do HIV care for five years or something like this. So it's just a thought.

I think you're right. There needs to be some real creative thinking about what to do because it is compassionate work to do what you're doing and I congratulate you and Bob Redfield and the rest of the people here that are doing that, Monica, but you just have to face the reality that people aren't going to do if they just flat can't do it because of financial problems.

DR. SAAG: Exactly.

MEMBER REZNIK: Dr. Yogev.

MEMBER YOGEV: I think you have raised the right point, but I think even you are late to raise the point of the crisis. It was there. It is there and in Chicago, there are two institutes and we are affecting the quality of the patient's right today because I know in Chicago there are three hospitals now that have a program and if you're uninsured, that basically does not allow you to admit a patient. You have to send him to the county hospital which are overwhelmed and the quality of treatment which was really good there is down and that's where are physicians are living and they have the best salaries by the way. So we are in the midst of a crisis and it's going to get worse.

Part of the population that I'm aware of that I'm sure you are dealing with a little bit is the adolescent. This is the second fastest growing in our population of new cases. I cannot admit into my hospital. I have a quota without saying it and what's interesting even in the Medicaid issue if you reach the age of 18, you get Medicaid. But after 18, you have to be AIDS. So everything which you did to prevent AIDS now caused them not to get Medicaid or Medicare.

So we are producing a population of uninsured. We have the disease, the beginning, the spreading, whatever and I think it's about time to move into really a national approach to it and we should consider for example B- are in the crisis to develop category special and to recommend to our government of a special entity that you can come and you can go out of special area in medicine that are in crisis that you need people, if you need them in the emergency room, there would be funding from the government to supplement this entity. If we decide the HIV, we need to recommend that HIV should be identified.

I was a little bit disagreeing with you with all due respect that training is enough in HIV. There are multiple studies and I'm sure you are aware of them that show that if you have less than 10 or 15 patients the quality of care you give them is not as good as if you have more.

DR. SAAG: I didn't mean to imply otherwise. I agree with that completely.

MEMBER YOGEV: I know, but it came out that training will be sufficient in the model.

DR. SAAG: No.

MEMBER YOGEV: It will not be sufficient. It will be sufficient to train the physician when to get the patient to the specialist, but those specialists should be identified and one issue would be to develop a system nationwide. You know countries who do it nationally are suffering less if you look at United Kingdom. I'm familiar with a system in Israel. The government is paying for those patients and removing a lot of the burden. So obviously, we'll never get to the government to pay for everything, but to develop this criteria that an entity like HIV will become preferred in whatever government, state will be paying on top of what you suggested.

DR. SAAG: I agree with you. I didn't mean to imply otherwise.

MEMBER YOGEV: I'm sure.

DR. SAAG: Sorry.

MEMBER REZNIK: Next would be Dr. Redfield.

MEMBER REDFIELD: Mike, I want to come back and try to be a little creative in how we put this together because the only way we run a financially solid program at Maryland right now unfortunately is it's driven by partnership on the Schedule A's for the hospitalization side which is really the wrong way to do this because as long as there are undiagnosed people who come in with an average CD4 cell count under 200 like as in Alabama which unfortunately the case in the State of Maryland also, we're still going to have people unfortunately find out their diagnosis largely probably a third of them by being acutely admitted to a hospital.

I've tried to create models at Maryland of this concept of cost avoidance and this is why I want to go back to McClellan and his group because if you take a clinic of 1,000 people based on Mike's numbers and you just switch their diagnosis from less than 50 to the greater than 350 for a clinic just with 1,000 patients you just saved on paper $23 million. My clinic you would save 4,000 patients. We'd save $92 million.

Now we are all of a sudden putting some money into a system and the problem with some of our health care finance situations is to look forward how we have cost avoidance. In other words, if we're looking for the current system to finance this, it's just going to keep going the way it's going. Schedule As, hospitalizations, are going to be driving the ability with outpatient clinics to work.

But one has to get more critical in looking at this. Now I couple that with my own view that I said about Ryan White. How do you do Ryan White funding? I'd like to link incentivizing Ryan White funding to those states to get the average CD4 cell count at the time of initial diagnosis going up. Those states that can do it at 250 or 350 or 400 I add I think they shouldn't be penalized for that. They should be incentivized for that.

So again, I think there is a critical need to figure because truthfully if it's just, I hate to say this, compassion or just try to get people involved, I don't think we're going to get the momentum to get the investment in the care system that we need. We need a sustained investment to build primary care for HIV infection, one, because we now know this is a process that if you do it right at the beginning, you could have a good shot at living a natural lifetime. If you do it wrong at the beginning, you have a good shot of not living a natural lifetime and yet we also know that we're at a climate now that we're going to move to earlier diagnosis. There are ways to begin to go higher CD4 cell counts, try to make the economic argument to someone that's thinking 10, 20, 30 years that the capital that is being used in this in the long term is actually we're saving long-term health care costs which are substantial for this nation.

So I think someone has to look at it because we're not talking about a band-aid here. We're talking about changing the financial hydraulics of what drives our investment in ambulatory HIV care at a federal level.

MEMBER REZNIK: Dr. Sullivan.

CO-CHAIR SULLIVAN: First of all, thank you very much for coming and brining us this message this morning because it's very dramatic and I think the discussion has been very good. I don't disagree with any of the things that you say. But the question is how do we dig ourselves out of this hole that we're in. That's going to be difficult because you talk to other areas of specialty, well, David knows that there was some NPR series on the news I think a few days ago. Some of you may have heard about the shortage, the crisis, in our nation's emergency rooms. So I think we will see that going around.

As I see it, we really have a situation where our leadership is really asleep at the wheel, Congress and the Administration. This is very different from what the situation was in the early `50s. Those of you like me who are old enough to remember there were reports of a pending shortage of health manpower and Congress got busy and passed a lot of legislation so that now today we have one in three medical schools in the country today had its origin in the second half of the 20th century. We're graduating twice as many physicians today as we were graduating in 1950, 16,000 every year as opposed to 8,000 every year.

Interestingly enough, we thought at one point that we had overshot the mark. You may remember the GMENAC Report in 1977 that said we had overshot the mark. Well, today, we really are approaching where we were in 1950. We've had a nursing shortage for several years that we really haven't been able to get serious attention and resources to address. We now have a pending physician shortage. The Association of American Medical Colleges I believe about four months ago put out a paper indicating or proposing that medical schools should increase their class sizes by 30 percent to avoid a shortage.

So I guess what I'm thinking is this. We certainly need to concentrate and bring to the public's attention all of these issues about AIDS, but I think this really should be joined with other issues. We're not going to solve this issue simply by focusing on AIDS when you see how emergency rooms are overwhelmed, hospitals are, etc. and we have this pending shortage of health manpower. It seems to me we need to find ways to join with other organizations like the AAMC, the AMA, the Dental Associations, etc., to really say loudly to the American people we have a problem that needs to be addressed because I can assure you many people are totally unaware of this. Now I think we clearly need to bring the attention of the American people to this situation in AIDS, but I think to really get the kinds of situations that we need this has to become a real national concern.

We have an election coming up in two years. Health care is going to be on that agenda. This is the time to really find a way to join forces with others to really try and address that because if this gets to be a real issue for the American people anyone who wants to be elected is going to have to address that.

So my suggestion is we need to certainly focus the attention of this council on the AIDS issue of the crisis that you have outlined so dramatically. But I think we also need to find ways to get allies and to join so that those emergency rooms that are overwhelmed, the rural communities that don't have physicians to really see some attention to their needs. So that certainly is an issue I think this council needs to be concerned about.

How do we really focus attention on getting solutions when they are short-term solutions to some of the issues here? But I think that's patchwork. I think we need to find a way to really address this. We did it as a country back in the `50s. We really are not doing it today.

The papers, The New York Times, has front page headlines about we to solve our nursing problem are really taking nurses from undeveloped countries and robbing them of their manpower. So we need to a much better job. I think we need to find a way to make this a more coherent strategy.

Sorry. One other thing, I think Joe and Frank also made good points. We spend too little of our resources on prevention because if we don't really change that paradigm we really are 30 or 40 years from now going to be having the same kind of discussion. So we do need to really find ways to improve the health literacy of our citizens, change their health behavior.

I thought we have a very interesting discussion yesterday. At least I learned something about how the different social patterns in places like India and maybe China that maybe the epidemic will be different there. So I think we need to find ways to really increase the effort on health literacy of our population and prevention as well because without that, I think we're going to be spinning wheels. They may be larger wheels, but we still will be spinning wheels some decades from now. So that's my comment.

MEMBER REZNIK: We have time for two more questions. Dr. Bollinger has been very patient and then Chris Bates.

MEMBER BOLLINGER: With apologies to Dr. Sullivan because I think his point was extremely important about a comprehensive and long-term approach to solving this problem, I want to move back to a more short term. One of the patches if you will and I apologize for that because I don't want to distract from the importance of your message, yesterday we heard from Marty McGeein about the reauthorization process. Now I'm not as intimately familiar with the process. Others here are, but it sounded pretty pessimistic about the logistics of the process, the funding that's being talked about for that. I didn't hear a lot that would really address some of the issues, the really important issues that you raised today.

One of the issues that occurred to me was actually brought up a few minutes ago by Bob Redfield and I wanted to ask a question and maybe some recommendations from you, Mike, about this. What he was talking about was incentivizing the process in a way that rewards programs that save money and one of the ways to save money that you've outlined is to diagnose earlier, is to get people into care and good care earlier with a higher CD4 count and right the system does not. In fact, it sounds like there's a disincentive to that.

In my experience at Hopkins in Baltimore and I want to get back to that question. There are two steps to it. One is testing people and we've talked about the universal testing. The second is accessing the care. I want to talk about that second piece or ask you about that second piece because there are quite a few patients I've seen in Baltimore who I know have been diagnosed before they came to see me the first time. They have complicated lives. They're active drug users. They were tested in pregnancy four years ago and never accessed care when they could have benefitted.

So I think there are sort of two steps to this. We could provide universal testing, but what suggestions do you have about improving the access to care or linking care to those earlier access points where we can actually get people into care at a more economically beneficial time?

DR. SAAG: Well, I don't know that I have a solution and since the time's running out, I'll just be very brief. I think that whatever testing is done has to be linked to care provision and that could be done out of physician offices with good referral connections to clinics or it can be done at the clinics themselves which are a little more difficult, although we've had a lot of success with rapid testing in our clinic itself and it's amazing how well that works and almost everyone who tests positive goes right into care.

But out-of-physician practices I think is where it needs to happen. I think free-standing testing is an option, but linking that to care is more difficult. So as a short answer, I would say that would be an approach.

MEMBER REZNIK: Thank you and Chris.

MR. BATES: Christopher Bates, office of AIDS Policy. Hi Mike.

DR. SAAG: Hi Chris.

MR. BATES: I'm really happy to see you here and to hear your comments this morning.

DR. SAAG: Thank you.

MR. BATES: I just have two comments that I think compliment some of what you said today. I've served on two panels, both in Philadelphia and Washington, D.C. attempting to try to recruit physicians and PAs to do this work and it's a bit disconcerting to after lengthy conversations, in-depth conversations with folks who were highly qualified that underneath their feeling really was hidden issues of stigma around working in this population, homophobia.

There was at least one woman in Philadelphia who just expressed to us that she was not interested in working with gay men or men who had sex. She was not interested in working with drug addicts in that her expectation coming out of medical school was to be working with a different kind of population. I think we can sweep that under the rug. We can't ignore that. This is not the same epidemic that manifested itself say in African countries and other places around the world. Our domestic epidemic is a real one based in populations that are highly disinfranchised and undesired and are general populations. So I don't want us to miss that as a contributing factor to the recruitment.

Furthermore, I would also offer up that as I've traveled around the country speaking on behalf of the Administration and the Department about our concerns and needs for HIV what continues to challenge me is the absence of a serious educational dialogue between legislators, both at the state level and the Federal level, outside of the AIDS epidemic center. The states such as New York and Florida, Texas and California, have very aggressive and very engaged delegations both at the state and the Federal level who are participating in dialogues about policies and funding as it pertains to HIV. That is not the case and even in our 14 southern states right now, there are heavily impacted with new epidemics.

So we have some imbalances here that undermine clearly our capacity (1) to keep a focus what those challenges are on a very personal way on the part of the legislatures. They don't understand what's even happening in their states. Many of them have not been to any of these provider offices or to clinics. They haven't seen this experience firsthand. So it doesn't mean the same and when talking heads and I don't mean to say that despairingly but when people from Washington, D.C. who are paid to lobby and paid to have these conversations professionally on the Hill I think it's not the same. It's not the same as seeing people from your district, people from your state, people who live down, who vote for you engage you in a conversation about the impact of this epidemic in a very personal, very natural way.

So I just wanted to offer those points up and then my last piece is it's not easy to identify people who don't want to come to terms with a potential HIV status. We have spent lots of time and money and hours training people to do outreach and going into very seedy and unsavory kinds of environments to connect with the most at-risk people if you will in our society and still with them knowing often times that they have HIV. What's the incentive to come? They won't be able to get ADAP in some states. Some states they may wait up to nine months for their first medical appointment and even in other places, the opportunities in terms of choice of where to go and seek services so you have some anonymity, some sense of confidence around your HIV status not being exposed, it's just not available. So it's an either or. It is a highly complex environment we're in right now with lots of challenges on many levels of which funding is key but not central.

MEMBER REZNIK: Mike, if you would hang on one more second, Dr. Sweeney promised me she would have two sentences. I'm holding her to that.

MEMBER SWEENEY: Joe McIlhaney mentioned raising money to pay off loans for people who wanted to do certain kinds of work. One of the things I think we should do is just look at the National Health Service Corps and expand it. The model is already there and it works very successfully. Some of my prime, my greatest physicians, have come from the National Health Service Corps. They meet their obligations and they stay on in the community health center if you make the environment right.

The other thing is there's another model that's used by the State Department called hardship pay. They pay special for doing special kinds of work in special kinds of environments. We can expand that. We can suggest that. We can't expand that. We can suggest it as a mechanism for getting people to do HIV care because as you've heard it described, it is special and hard.

And the other one is there is a shortage of physicians going forward, but there is also a great maldistribution and there is a model. I worked in Columbia, South America when I was doing an externship there. They have something that every physician who is going to get licensed to practice has to do time in what they call Rual. And so everyone, it's a privilege still in 2006 to be a physician. Pay for the privilege even if you're rich by doing some time working in populations that are health-power shortage areas. So there are lots of models that we could look at to help while we're coming up with better solutions.

MEMBER REZNIK: Dr. Sweeney, if that was two sentences, they were too very long ones. But thank you. Dr. Saag, I want to thank you for taking the time out of your busy schedule to come and present to us.

(Applause.)

MEMBER REZNIK: For the members of the Council, please during your break or during lunchtime look at page 38 which is where we did have some recommendations on training medical professionals in quality assurance and hopefully we can come up with a motion today.

I'm running behind schedule so I have to introduce our next speaker who I think has to catch a plane. I'll do a brief introduction on Dr. Cohen who is the J. Herbert Bate Distinguished Professor of Medicine, Microbiology and Immunology and Public Health at the University of North Carolina at Chapel Hill. This has been a North Carolina few days.

You can see his bio which is pretty much an incredible biography. He is the Director of the NIH STD Clinical Trials unit. He is Director of UNC Division of Infectious Disease and the UNC Center for Infectious Disease. Quite an incredible track record. Over 400 articles published. Much of Dr. Cohen's work has been conducted aboard especially in Malawi and the People's Republic of China. So if the members could come back to the table and the audience settle back down it's been a great honor to introduce Dr. Cohen.

(Discussion off the microphone.)

MEMBER REZNIK: Okay. Dr. Cohen is being gracious and is going to give us a five minute break. Did you all hear that in the back? You have five minutes.

(Whereupon, the foregoing matter went off the record at 10:18 a.m. and went back on the record at 10:29 a.m.)

MEMBER REZNIK: Okay. Good. That was a long five minute break. I've already introduced our next speaker. So without further adieu, we'll let him get his system in gear. Are you plugged in?

DR. COHEN: Maybe. Is this working now?

MEMBER REZNIK: There you go.

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DR. COHEN: Okay. I think we're going to start. Is that correct? Let me indicate thank you for inviting me. I was in London yesterday. I've been living in London for awhile. So my jet lag is enormous. So we'll see how much disinhibition I have this morning. I got here. There was a thunderstorm. I got here like 2:00 a.m., slept for an hour, came over here and I've not quite an idea of how this is all going to turn out.

Let me say from listening and being in academics I was restrained for like an hour listening to Mike Saag and my colleague. Let me say that what we're going to talk about now is really prevention of HIV and I think one of the big issues without a doubt has been marrying prevention and treatment as several in this panel already said. It makes no sense to believe you can treat your way out of this problem without much more intensive prevention activities where we've not done a good job by any measure. We've not succeeded in prevention in the United States and certainly not on a planetary level. So we have to hope for better strategies for the next 20 years.

Now I'm going to talk almost exclusively as a biologist, as a translational biologist. So I'm going to go slow and show slides and kind of explain where we think we are in terms of transmission understanding which leads us to prevention strategics. But let me say that there's not doubt in my mind in terms of physician recruitment and education and training that the person who goes into HIV medicine or the next generation has to be somebody who is interested in public health as well. The responsibility isn't just about knowing about the medications. The responsibility is understanding about the community and about the issues that surround HIV transmission.

And I think that if I was a fund raiser, there's no doubt. Why should somebody want to pay for HIV treatment instead of diabetes treatment as Dr. Sullivan kind of was alluding to? Well, the big issue here is this is a transmissible disease and the more that the treatment and the activities that surround the treatments are wetted to prevention, the more it's totally different than all the other diseases on the plate of all the funders and I think it would be a tragedy not to end this dichotomy and make this an absolute commitment.

In the report that I participated in supported by the CDC, the IOM Report of 2000, HIV Prevention in the United States: No Time to Waste, there's a whole chapter devoted to prevention in the treatment setting and the obligation of the medical community to learn about preventions. So having said all that, this is really a prevention talk that I'm about to give.

I'm going to go faster with things that I think you've already talked about and the slow down when I think there are new ideas and there is no tradition of interrupting. Is that correct? There's a hesitation to interrupt, but I would prefer actually for this kind of a talk to be interrupted and Frank I know will be glad to interrupt. But I prefer to be interrupted because why go on if there's something that makes no sense or that is so argument evoking and so controversial, why go forward? Why not just have the controversy right then?

So basically, this is the bottom line. This is a biological event. HIV, you don't get a little HIV or a lot of HIV. As far as we know, there is the transmission event and the transmission event is dependent on infectiousness and susceptibility. And we're really certain that the concentration of virus in the genital secretions or in the blood, but especially the genital secretions, are going to explain most transmission events and this is not rocket science. Most infectious disease depend on the inoculum. So we're very concerned about inoculum.

We're also concerned about viral phenotypic factors because we're reasonably certain that the type of HIV we have in the United States, clade B or Type B is not as contagious as some of the clades in other parts of the world. So while we see people living in other parts kind of mislabeled as misanthropic sexual people, a lot of this epidemic has to do with biological disadvantage and we see that biological disadvantage at some level in terms of inoculum and phenotypic factors.

We see it played out even more aggressively in susceptibility. We know that about one out of 100 white people have a hereditary resistance factor to HIV. Resistance is very rare with people with color. We know that there is innate resistance in some white people and we know that there might be some people with acquired immune resistance which would help us to make vaccines. We'll get to that later.

So infectious and susceptibility equal a transmission event and if you're lucky, you don't have to a transmission event and if you're unlucky, you have a transmission event. Our job is of course to prevent this transmission event.

So this is kind of a starting point. Now I'm going to criticize this article heavily because it's just wrong and this is an article I wrote in `97. So as I attack the author, I want full B- If I'm attaching my friend, Ward Cates, it's because he and I wrote this together.

We knew really with great certainly the transmission probability from mom to a baby and we knew the transmission probability from needle stick to the next person and we knew that because we have the mom and we have the baby and we knew that because we have the needle or the unit of blood and we have the subject who was exposed. So these numbers could be decided on with great accuracy and have been tremendously validated over the years.

But these sexual transmission numbers are an incredible mess and I won't tell you how we got into this mess, but that mess has helped give a bad message to people. That message that we've sent to people is that it takes thousands of episodes of intercourse for HIV to be transmitted and that really is not true basically. These numbers, and if there is time for the discussion, I can explain how we made such a mess out of this, but the methods we used confused the message and we used a set of methods in the late `80s, early 90s, that it made an incredible mess out of our understanding of HIV transmission.

Now how do I know this is such a mess? Well, look at my colleague, Audrey Pettifor, working in South Africa. She's doing a national survey in South Africa of boys and girls, males and females, and she sees a low prevalence in young people just as they are becoming sexually active. This right off the bat gets us into this whole needle stick argument and almost gets us away from it the idea that the whole HIV epidemic is being construed on the back of needle sticks just doesn't hold water.

So let's forget about that and let's say these people are now becoming sexually active and you see the young boys have a low prevalence sustained over a fairly long period of time, but these girls acquire HIV at an incredible rate. About one-third of the girls in South Africa by the time they reach 21 are HIV infected.

Now I would submit to you if that was going on in the United States, everything would stop in the United States. Somehow people are tolerating this or at least living through it in South Africa, but the bottom line is when you ask these girls how many partners they have, are they having anal intercourse, how old are their partners, you don't find data different than the United States. We've done similar studies called Add Health in the United States and the data is not different in South Africa. So some different kind of events are going on in South Africa. We would argue that they are mostly biological than behavioral and that the transmission probably is not 3,000 episodes of intercourse. It's more like 20 or 30 episodes of intercourse. So the first shocking message is that HIV is not so inefficient.

And we know that most people on the planet have sex about eight to ten times a month until they started getting older. I'm not going to go into that too much. But if you look at the young people here 15 to 24 studies have been done in China, Chicago, France, England and there's all these books, most by a guy named Laumann called Sex in France and Sex in England and Sex in China and when you do very careful surveys you find out that people have sex about eight times, ten times a month. It's very difficult then to get to 3,000 episodes of intercourse for most of us in this room, maybe even in a lifetime let alone in enough time to have a transmission event.

Then you see as you get older, we start lumping the numbers because sexual intercourse really gets reduced and I don't want to get too personal about this. But the number could get below the line. Actually if you extend this out because you're telling people not be sexually active. So it gets lower and lower and lower. But the point is that we don't think that the transmission probability is published throughout the `80s and early `90 are correct and we think some other better explanation is necessary.

And that leads us to the idea of amplified transmission. If the rates are too low, we think HIV transmission is intermittently amplified by increased general tract setting of HIV and an amplified transmission will help us to understand the epidemic and maybe allow us to redistribute some of our resources for prevention a little bit better.

So these are the ideas about amplified transmission. There are different sets of ideas. For infectiousness, we are very concerned about the stage of the disease, co-infections that might drive up the blood and general tract viral burden. STDs are a huge factor, classical STDs are a huge factor in the transmission probabilities and then genetic factors that might lead somebody to have a higher viral burden and remain more contagious over a longer period of time and I'll show you some data about that.

Susceptibility would depend on STDs, vaginal flora, mystical innate immunity and again genetic factor that we think we've only scratch the surface on. Only one or two genetic factors are understood in terms of susceptibility. Go on.

MEMBER BOLLINGER: Would circumcision go on the list?

DR. COHEN: Yes, circumcision would be on a prevention list.

MEMBER BOLLINGER: That's not a susceptibility factor?

DR. COHEN: It will come later. Thank you. So circumcision could be a susceptibility factor, but it will come up in our discussion of prevention. And so we think probably this slide is correct that the concentration of HIV in ejaculate will predict the probability of transmission depending on the number of endocervical receptors. We're able to measure all three things. We can collect ejaculate from people who are HIV infected and we can measure how much HIV there is. We can actually do biopsies of the endocervix and see how CCR5 receptors there and how many CD4 receptors there are and so on and so forth and we can calculate these curves and you see that the HIV transmission probability at an HIV copy number less than 1,000 copies per mil of semen is probably very close to zero, whereas the HIV transmission probability at about 100,000 copies in semen is probably about one in 300.

And when you get up to 1,000,000 copies of HIV in the semen or the female genital secretions, you're probably getting much closer to a transmission probability of about one in 30. So if you have like numbers of chambers of guns to your head, if you use that metaphor, you can see it's not 1,000 chambers. It's not this message and I was kind of totally shocked to see the Minister of South Africa and I'm sure all of you in this room are familiar with this story having sex with so many newly infected and then quoting an article from the `90s saying he quote Nancy Padian's article which we think is wrong and said, "I read this article. It says that you need 1,000 episodes to get HIV infected. Therefore this was a low risk event for me." So that was the most misanthropic message I've ever heard sent. We think that this slide is correct.

We also think this is correct within reason and I'm going to come back to this slide a couple of times. So we think that someone's HIV negative here, they acquire HIV, they have ramp-up viremia and in this early window of viremia, they would be very contagious because of the very high general tract viral burden, maybe only 30 episodes of intercourse are necessary and then some people will get very low copy numbers and those people might transmit at very low level. But then we suspect that as HIV infection advances people don't become so sick that they're not sexually active. They remain sexually active even unto being admitted to the emergency room with a low CD4 count. They might have been sexually active that day. So some percentage of patients with AIDS or people with AIDS will also transmit disease.

And we only have one piece of data about this but it's a very compelling piece of data. From the Rekai study (PH), there were 14,000 people who weren't really couples. They were assembled as couples later. So all 14,000 people were in a closed community and what they found was that in this Rekai study as they measured the transmission events that occurred in this closed population that 43 percent of the transmission events occurred at the earliest point in time that they could measure. So that meant that there were two negative people enrolled in the study and by the next time they measured both people were positive.

So obviously a third person got into that relationship. The two negatives both became positive and what we expect happened or suspect happened was that one person got acute HIV and they immediately transmitted it to their next partner allowing this event here.

Then in the Rekai study, almost no transmission events occurred in people with established HIV infection until people became much sicker and were very close to death. They remained sexually active and then about 16 to 20 percent of transmission occurred at the end of this window of time.

Now I just want to remind you that most of our HIV prevention efforts are focused on the middle of this curve, on people with established infection with fairly low CD4. We've had no, very little HIV prevention efforts in people with AIDS and I think the HHS has done a good job in trying to launch much more aggressive interventions here and we've certainly not done anything with acute infection for a whole bunch of reasons. So this is kind of where we are and this is a very compelling study.

Can you all understand me at this rate of speed? Okay. Then I'm going to talk faster. So one issue here is about acute HIV infection. Now it's not to say even if it's true that almost half of all the infections are accruing because of acute HIV infection. It's not to say that we believe that suddenly this could become a giant public health maneuver. It is to say that it is something that we really need to understand in the next five, ten, fifteen years for a whole bunch of reasons that we might want to talk about later.

So we spend a lot of time trying to develop a way to diagnose acute HIV infection. Historically, people look for symptomatic subjects who are at risk and about half the subjects at risk have some sorts of signs snd symptoms when they acquire HIV infection. But the signs and symptoms are so vague you couldn't possibly separate them out. In an epidemic with 60 million people, less then 1,000 people with acute HIV infection have been found by diagnosis which is kind of amazing.

MEMBER McILHANEY: Excuse me. Did you say it's not true to say that half of new infections occur in this early stage?

DR. COHEN: I think it's true to say B- No. I think if we go back to this slide we have one piece of data and that one piece of data is right here and it says that 43 percent, in this study, of all the HIV infections that were observed seemed to have occurred from the earliest stages of infection.

MEMBER McILHANEY: But did you say that it's not true to say that about 50 percent occur in the early stage?

DR. COHEN: Well, I wouldn't generalize it because we only have this one piece of data.

MEMBER McILHANEY: Okay.

DR. COHEN: In other words, if you were going to say I have a single study that shows that this might be important this is the study.

MEMBER McILHANEY: Okay.

DR. COHEN: But if you were going to try and extrapolate that to the whole planet, it would be a problem.

MEMBER McILHANEY: Okay. I just want to be sure.

DR. COHEN: And I think B- I know we kind of oversold this a little bit. It's my group that's been doing this work and I think we've oversold it a little bit and I'm trying to be a little bit sensitive.

MEMBER McILHANEY: Yes. I understand what you're saying now. I just wanted to be sure.

DR. COHEN: No. Thank you. Other question before I go on? So the symptomatic idea is never going to work. So we tried another strategy and we intend to continue to pursue the strategy in the next couple of years. So here is the HIV negative person and this is actual data of people being followed in a blood bank. Sometimes people have what's called blip (PH) viremia. They may or may not go on to HIV. So this is very intriguing. We have about 12 people with this blip viremia and whether they all go onto HIV or not is not known.

But most people clearly when they get exposed, then within two or three days after exposure they have ramp-up viremia and for reasons we don't understand completely there is tremendous and rapid replication and people achieve a peak of a million to a billion copies of HIV and as they're achieving that peak, they're antibody negative. So if you went to a clinical and said test me today, you would be at your most contagious of your whole life, but you would be antibody negative.

Now of course the antibody test can get better and better and better. But they can only get so good because the host requires several weeks to make antibodies. That's the rule of our species. So matter how good the antibody test gets. there's always going to be this window period of high contagion in an antibody negative person.

I should point out to you that it's during this window of time of rapid viral replication that the host is undergoing a terrible destruction and that is we're pretty sure now that CD4 memory cells, the central memory cells, living in the gut are all wiped out within two or three weeks. We have this experience now kind of written in stone with monkeys where if you take a monkey and you infect him with HIV and you follow their gut lymphocytes in what's called the central memory pool, it's destroyed in weeks and now biopsies have been done a humans with very early and acute infection by again Danny Douek showing the same thing. This is terrible irreversible damage. So whatever CD4 you end up with after you recover from your acute infection, you never have the same number of CD4 cells available to you as before this gut pool is wiped out.

This inspires in us a desire to really think hard about trying to prevent this event. So if you're going to say to me how are you ever going to find all these people and why would you want to find them, one reason we want to find them is to protect these CD4 cells because this is the No. 1 devastating event that occurs during this window of time.

The other devastating event that we're pretty sure about is the integration of HIV into the genetic material of the host. So when you start out, your genome actually has a lot of retrovirus from millions and millions of years of evolution. About six percent of the whole gene is retroviruses. But you don't have HIV incorporated in your genome and so in the very earliest days of HIV infection we can see a very small number of integrated events, but then after acute infection has transpired, we see a heavy dose of integrated events. The reason we can't cure HIV infection is because of the integrated DNA. So if we could deal with the integrated DNA, get it all out of integration or prevent it from ever being integrated, we could potentially cure this infection. So we have a lot of reasons to be interested in acute HIV infection, surveillance for instance, prevention and earlier treatment and so on and so forth.

Now I've argued that we can see a huge coy number and no antibody. So it's not a big leap of faith to do what the blood bankers do. So let's go back to `87 and almost everybody in this room was working in this field in `87. And you'll remember in `87 and Dr. Sullivan will remember this perfectly the transfusion field was in terrible trouble and we were able to do antibodies to find contaminated units of blood but about eight or ten or 20 units of blood would slip the antibody testing and as soon as the PCR test was available for detection of HIV, every unit of blood in the country was submitted to a PCR test.

Now it's estimated by my friends in modeling that it costs about $80 million to find the last eight infected units of blood in the United States, but that had to be done in order to get people to feel that the blood supply was safe. That was really not an option.

With the blood supply people did was they did pooling and they took 100 samples and they put them all together and if everything was negative in 100 samples, they went on with their business. If one sample was positive in 100 samples, they would go back and break apart the whole blood and find the one infected person. This saves a lot of money since you're not paying $50 a test. You're doing $50 for 100 tests. And remember because of this ramp-up viremia, there's a lot of virus in the blood of people with acute infection.

So the State of North Carolina led by Peter Leone who talked to you yesterday, he's the Medical Director for the state, they agreed to screen everyone in the State of North Carolina for acute infection. So we're going to look at all of our testing sites. We're going to find 563 people with new HIV infection detected by antibody. Those are over here and then we take all the negative samples. They go to a robot in Raleigh, North Carolina and the robot every day does 1,000 samples and when we do that we find 23 acute infections which seems like a small number, but that's five percent of all the infections detected in the State of North Carolina. For every one of those people with acute infection, we start finding a cluster and Peter talked to you yesterday about social networks from clusters. Right? So you see how powerful this becomes because of clustering and snowballing. So the state committed to this and many other states are looking into this for obvious reasons.

The copy numbers are important. Here is the copy number of control subjects with established infection. We're looking at blood, not semen, but you see in the United States it's about 29,000 copies at set point and the acute infection patients it's about 210,000 copies in acute infection and then this guy has more than a million copies. So the transmission probability of this group is about one in 800 or one in 1,000. The transmission probability of this group is about one in 100 to one in 80. So we see a huge difference in the United States of these transmission probabilities as calculated from the data we collected.

And for every person we find with acute infection, we find a terrible thing really. They don't have one partner. We find three or four or five partners. And there are three universes for the partner. The partner can have established infection and they could have given their established infection to the person with the acute infection or the partner can have acute infection or the partner can be HIV negative. Of course, the partner who is HIV negative becomes an unbelievable prevention effort for us to prevent a transmission event from occurring and the partner with established infection or acute infection also becomes important to the overall prevention strategies for our state.

And what's important is where do we find these people. So here are the testing sites, STD clinics, HIV testing sites, prisons and jails and other. Most of the testing in most states goes on in STD clinics and remember this is bias because we have opted in testing. This is less than half than all the people who have come to STD clinics in our state. So we don't know what happened to the other half of the people. We only know what happened to this half.

But we know that we find established infection, recent infection and acute infection mostly in STD clinics and as I'm going to tell you in a second, this isn't surprising because we think HIV transmission is primarily B- Well, first of all, HIV is another STD. So it's the same behaviors that lead to STDs lead to HIV and second, we think that much of HIV transmission is actually a two step process. It involves a classical STD as well as HIV.

But what's important here and now B- Is anybody here representing the CDC officially? Many of us are on a committee. Many of us are on the same committee where we've talked about this. I can't say enough times how I can't believe we can't get the STD clinics in the United States to work to do testing for every subject who goes into an STD clinic because this would be the biggest no-brainer way to find a huge number of people who don't know their status and to find people with acute infection and we've been telling the CDC this for at least five years and, Frank, you might want to comment on this.

MEMBER JUDSON: We're already doing it.

DR. COHEN: You personally have been doing it.

MEMBER JUDSON: Yes.

DR. COHEN: You're trying to do opt-testing on very client who comes to your STD clinics. But you realize nationally that's not the norm. That's not the national norm.

MEMBER JUDSON: I think it's a lot better.

DR. COHEN: The more it's done the better it is. Anyhow, this is a soapbox. My only soapbox for this morning is that B-

CO-CHAIR SULLIVAN: Why has this CDC not responded to that?

DR. COHEN: Do you want B- This is just by sheer option and others in the room are on committees with me that work with the CDC. I think that first of all there's kind of an internal turmoil for many years about the STD branch how independent is it or how much does it report to the HIV branch. The HIV branch's interest in STD waxes and wanes. The kind of belief of the importance of STD, sometimes they believe they're important. Sometimes they're not so interested. So the two groups don't really work seamlessly in my opinion, STD and HIV groups. They should work more seamlessly. That's the first point.

The second point is the CDC gets like anything else it's an organization led by talented individuals who get on their kind of issue. So they've been very interested in emergency rooms in the United States and I say, look. If you're going to test everybody in all the emergency rooms in the United States, you don't own the emergency rooms. It's a tremendous effort. But you own the, you don't own, but you support every public health STD clinic in the United States. So the energy necessary to do opt-out testing in the United States is very small, the catalytic energy compared to testing everybody in the emergency rooms.

But they've had this internal debate about emergency rooms versus STD clinics and this is just dragged on and on. I've gone to the CDC personally three times to give a talk like this to say test everybody in the United States.

Now to defend the CDC, they're trying to do opt-out testing. They're trying to get every STD clinic to lead towards opt-out testing. But I think a forceful statement from this committee would be helpful.

MEMBER JUDSON: Having started my career at the CDC and been involved with the CDC ever since, the problem isn't so much individuals at the CDC who get into their own thing and want to protect their turf. I mean it is, but the primary problem is that Congressmen and Congress people like categorical programs. They like to have their name affixed to it. They want to see an outcome. They want to know where the money goes and that it's accountable.

So that some of the biggest attacks on the CDC have come when the CDC has attempted to use money for one project in another project area. So they drive it for TB, for respiratory distress syndrome, for anything.

DR. COHEN: Let me say I don't it's a turf. I don't think this is an issue of like some B- I think it's people's interest. If you're interested in herpes, you're interested in herpes. If you're interested in HIV, you're interested in HIV. Sometimes the people wouldn't necessarily see the connection as clearly we might want them to.

MEMBER JUDSON: It's like the silo thinking starts with Congress.

MEMBER McILHANEY: I'm on Dr. Gerberding's advisory committee and one thing you pick up is that they feel like they obviously cannot mandate that all STD clinics in the United States do this because they don't control them like that and I think there's a little bit of paranoia about issuing proclamations that I think they're wrong about. I think they should do exactly what you're saying and I think sometimes they underestimate how much influence they'd have just saying all STD clinics should do this.

DR. COHEN: Right. Of course, they do B- First, I'm sensitive to what you said. But I do think they do issue proclamations all the time limited by money. They say if you don't meet this goal, we're not going to give you Title X money. That is their only control over the public health plus they provide public health advisors.

But also I don't think there's a tension here. The STD clinics would love leadership from the CDC. I can't imagine any STD clinic not being thrilled about being told if you do this is going to benefit the people of your community and your state.

MEMBER McILHANEY: I totally agree and some of us keep pushing them to do what you're saying.

DR. COHEN: Okay.

CO-CHAIR SULLIVAN: Let me just say I think our Prevention Committee ought to look at this issue, because I do think that perhaps some support from this council might be helpful. I can understand CDC really battered from all side, etc. but it seems to me that one purpose that we could serve is to really point out to not only CDC but the members of Congress about the importance of this.

DR. COHEN: I can't see how you can B- If you tested all people who went to visits to STD clinics in the United States you would without doubt drastically increase the number of undetected people living in the United States.

MEMBER REZNIK: We'll come up with a motion at lunch. That's No. 3.

DR. COHEN: All right.

MEMBER REZNIK: I like fast. You talk fast. I write fast.

DR. COHEN: Let me keep going then. Do STDs play a major role? There are tremendously compelling pieces of evidence that HSV-2 which is really an aggressive virus trying to fill up the entire planet. Right now, at least about 20 percent of Americans are HSV-2 infected. That number is almost certainly going to climb in the absence of some mystical intervention. So I think for many people HIV transmission looks like that HSV-2 is transmitted much more efficiently than HIV. Probably it just takes a few episodes, two or three episodes of intercourse for HSV-2 to be transmitted.

So an HSV-2 negative young person has their first encounter with an HSV-2 host. Now the HSV-2 infected host may not know they're HSV-2 infected. I"d say less than five percent of people have symptoms and signs that would lead to know their status. So they've unwittingly given HSV-2 to the partner. The HSV-2 causes endocervical and penile skin changes that render the host much more susceptible to infection. A really important abstract is going to be presented at the meeting in Toronto that were biopsies done on the women who had recently acquired HSV-2 and demonstrating beautifully visibly how many more receptor cells there are and how many more receptor per cell.

So the first stage is HSV-2 transmission or maybe syphilis transmission or maybe gonorrhea transmission or maybe trichomonas transmission and then the next stage is HIV transmission not requiring 1,000 episodes of intercourse, now only requiring maybe not even 30 episodes of intercourse, maybe requiring only ten episodes of intercourse because of the tissue changes inspired by the classical STD.

So there is no doubt about this. What's gone wrong in the STD field is that the clinical trials the STD people have tried to do to demonstrate that intervening with STDs can prevent HIV transmission, those trials have failed miserably and that has caused tremendous policy consternation which is going to be played out at a WHO meeting on July 11, the big showdown between the policy people who don't want fund STDs as part of the HIV portfolio and the people who are saying that's insane. It's just that the trials didn't work out. It's not that STDs aren't important. So this is kind of where we are with that issue right now and many of us are going to that policy showdown meeting.

So let's move to Africa just for fun because I want to show you something about transmission in Africa. I work a lot in Malawi. We've worked there since `90 and we worked there for a very specific reason. We wanted to see the effects of STDs on HIV transmission. If we're working in a U.S. clinic, we'd have to work for years to see a transmission event. But in Malawi, we're in a country of 10 million, 90 percent rural, about 15 percent adult prevalence but in the STD clinic we run, half the people are HIV infected. So one out of two people who come in are HIV infected.

Obviously, this is a human laboratory where we can learn things very quickly and we with the help of the U.S. Government and international funds built a research center called Tidziwe Center that we're extremely proud of. That's it in its construction.

And this is just a study that I want to show you. It's published with about five other studies like this, but this is 1,361 men screened and 47 percent were antibody positive. So we take the antibody negative people and we say these are people who are going to be sent home. We say do you have acute HIV infection. What we found to our shock was about two percent of people have acute HIV infection which is a very high number. Bob Bollinger did the first study like this in India, very similar study and found more than one percent, greater than one percent. So Bob actually led the way. Let me give credit to you because it was a brilliant study using p24 I think.

So the point is this has been repeated over and over. If you go to STD clinics, you look at the negatives. You're going to find some acute infection and what's even more shocking is if you have a swollen gland and a general ulcer, exposure to sex and you're HIV negative you have about a ten percent chance of having acute HIV infection.

This is the viral burdens now in Africa. The antibody negative people have higher concentrations than they would in the United States. Here's 150,000 copies at set point. So the Africans are managing to have much higher concentrations of the virus. Why? We don't know. But that increases the transmission probability. If you look at the acute infection patients, it's one million copies median. This is two billion and this is three billion of copies of HIV. So the median transmission probability in Malawi for the acute infection people is about one in 30 and this guy is 100 percent transmission probability.

So what am I saying? I'm getting you away from the `97 article that had one in 1,000 transmission and I'm saying that's not true. The transmission probability is going to be predicated by where you are in the disease and whether you have an STD and you shouldn't count on 1,000 episodes of intercourse before you acquire HIV. You should count on one episode of intercourse before you get HIV. It's a very different message than what we sent out in the published articles and not everybody agrees with this. So you're only hearing my opinion.

Here is an interesting unpublished piece of data. Now we're actually collecting semen in the clinic because we want to see what happens over time. The blood is in red and the yellow is semen and what happens is the blood is sustained, but the semen viral burden goes down precipitously after we treat the STD. So the maximum contagant for semen is only a few weeks. So this is a pretty interesting finding to us from a public health point of view in terms of how we're going to manage it.

MEMBER JUDSON: You're saying not everybody agrees with that. Who with an infectious disease background and who understands simple mathematics of transmission and inoculum would not agree with that?

DR. COHEN: Let's leave this. We have hours to go before we're done. Let me leave your question. We'll get to who might not agree with this and why people might not agree.

Okay. So now we come back to this slide and this is now we have to dissect this better. So I've kind of made my argument in the most aggressive way I could make and now I'm going to break my argument apart and show you something a little different. I think it is true, this gets to Dr. McIlhaney's point, I think it is true that some substantial number of infections occur in the earliest days of infection. Whether it's ten percent, twenty percent or it's fifty percent, I don't know, but it's not a good time to be having unprotected intercourse with somebody.

And just because they told you I got tested last month, that ought to be a sign not to have sex with the person because why were they being tested last month? Obviously their risk behavior sent them to a clinic to be tested. So it's kind of interesting. Remember we had, I mean this goes back to the `80s and `90s, the whole idea that recent antibody testing sets the stage for a safe feeling. People were going to have a card to show you they were antibody tested, stamp it on their hand. Remember all this. Well, that actually to me would be a symptom that you really don't want to have sex with that person for obvious reasons because they might have antibody negative acute HIV infection and be most likely to infect you.

Then we have this incredibly idealized vaccinated person or person who's called an elite controller who suppresses virus to few copies and no transmission events occur. This is not true. So this is what actually happens. Ramp-up viremia and then set point and only less than one percent of people who get HIV can do this. In fact, people spread their virus out over a whole spectrum of HIV concentrations. Now the person with the highest concentrations sustained at what's called set point. How you achieve set point we don't know. Is it genetic? Is it immunological? Is it virological?

All we know is at six months or nine months or a year into your infection, you've achieved some sort of state and if the state you achieve has a very high viral burden, then death is more rapid and transmission is more likely. But if you're lucky and you are lucky enough to have a very low concentration of virus in your blood, you're probably much less contagious and you certainly will live much longer.

Now there's a mathematician named Christophe Fraser, F-R-A-S-E-R, and he says that "the virus is seeking an optimal concentration" and what he means by that he thinks that the virus wants to spread to as many people as possible and the way that the virus can do that is to kill the fewest hosts possible. So what he says is that the virus is trying to achieve five logs in the blood of people. At five logs, the host lives many years and the host remains contagious enough to send the virus to the next person.

What's interesting about that five log deal is that the Africans generally sustain about five logs of virus. That is the most common set point, 4.9, 4.6. So Fraser obviously modeled this based on what he was seeing but it's an interesting kind of Darwinian evolutionary argument. So he doesn't believe that acute infection is important and he doesn't believe that AIDS is important. He certainly doesn't believe that most people get this low set point. He believes that all over the world where there's five logs, it's that five logs that's really critical to sustaining this epidemic.

EXEC. DIRECTOR GROGAN: When you said the Africans are around five in contrast to what other?

DR. COHEN: U.S. are like 20,000.

EXEC. DIRECTOR GROGAN: And where in the U.S.?

DR. COHEN: About 18,000 to 20,000. So if you look at the U.S., I mean it depends on the person, but we've not B- If you took 1,000 U.S. people untreated in Bob's clinic in `90, most would not have 100,000 copies. Most would, I think, have 20 or 30.

MEMBER REDFIELD: When we looked at the Defense Department a number of years ago.

DR. COHEN: How many subjects?

MEMBER REDFIELD: It was a large number.

DR. COHEN: Thousands?

MEMBER REDFIELD: Yes, but it was the average viral load was between 9,000 and 10,000.

DR. COHEN: Untreated.

MEMBER REDFIELD: Untreated.

DR. COHEN: So if you took an untreated African population, the average would probably be between 100,000 and 200,000 copies at the same CD4 count. I'm only telling you the facts, Joe. I'm not going to explain them.

MEMBER SWEENEY: So many people go in and out of treatment with antiretrovirals. Given what you've just shown us, if someone is not going to be able to be on sustained therapy then, it seems that they reach their set point and it would be better to just leave them at the set point without treating them instead of having B-

DR. COHEN: Let's leave the treatment issue for a second except to say one thing. We're going to come to treatment in a second, but let me just say, and I appreciate you're still awake, but let me say that the whole issue of treating people earlier, treating them for public health purposes and starting and stopping therapy is very controversial. But certainly we know for sure that starting and stopping therapy based on a study that was just completed is probably a really terrible idea. We know that if you start therapy early, at least from one or two studies, if we start therapy early and you can sustain the therapy and people are adherent, they do very well with very early therapy if it's sustained, but not if it's started and stopped, not if they leave it.

MEMBER YOGEV: I hope you put into the argument the guidelines now say don't treat if it's 100,000 unless B

DR. COHEN: I don't know. I mean guidelines B-

MEMBER YOGEV: From the public point of view for to just showing us B- Would you address that?

DR. COHEN: Yes. I think the guidelines that we've written are we get into an issue Mike B- The MP chair is Mike Saag. He is the guideline guy and the guidelines in general on the treatment of people in general have not paid much attention to their public health obligations and responsibilities. When Tony Fauci got into a whole big interruption, vacation holidays, drug holidays, we called him and said, "Are you crazy? This is exactly the most destructive thing you could do, render somebody feeling better, stop their drugs so they have a rebound," etc. So we had great trouble with what they called STI, strategic treatment interruption, which we called sexually transmitted infection. So even the language is a problem, but I mean complicated.

STDs, one last point about STDs, if you take a person with gonorrhea, this is from a study that was published in `97, you take a first week of infection. We're looking at semen. You see 150,000 copies in semen and over time you see a very rapid lessening of HIV concentration. So this is what we think is a more realistic picture. Ramp-up viremia, some control, but not that level of control. But then the person with HIV doesn't remain a newly found virgin. They go out and have sex and a substantial number of people who are HIV infected acquire STDs. We know from most studies in the United States it's probably about six percent a year, five percent a year.

So that is a sign that our counseling in clinics is not optimal because so many people who are HIV infected acquire STDs and when you acquire an STD even on ART, you can break through the ART. So if you're not on ART, you are for sure going to increase your concentration of HIV in your genital secretions. If you are on ART, about ten percent of people break through the ART. When they break through the ART, they have resistant virus breaking through especially protease resistant virus.

So now we're beginning to see how we're going to blow our drugs. We're going to take all the drugs we've made and we're going to see transmission of resistant virus to the next person. Therefore, we're going to be in a constant race to make drugs that are going to be effective for newly infected people.

Now this is not completely played out yet. It's played out at the level of 16 percent, 15 percent. So if you went to Bob's clinic and we did single gene amplification, we would find at least 15 percent of his new patients have resistant virus. How did they get their resistant virus? Either they were seeing a patient on therapy who got an STD and broke through or who stopped their therapy either transiently or completely and had resistance develop.

Somebody had a question or not? Yes. Isn't it more fun when you interrupt? Isn't this a lot more fun?

MEMBER GREEN: Putting this in the context of prevention, I'm thinking about the multi-site study in Africa that was published in the special issue of, what was it, anyway in 2001, Journal of AIDS, I think. When they looked for factors that seemed to be causally associated with higher or lower levels of HIV prevalence as you recall there were biological factors such as presence of GUD especially HSV too and male circumcision were the factors. The only behavioral factor that emerged in the first round of analysis was the pattern of older men having sex with younger girls and I remember thinking and discussing with people at the time one reason for that would be that a young girl when she's recently infected she's lost her virginity. She probably would be susceptible to having sex with somebody. Older men are thinking if the girl is young, she's probably not infected, but they are more likely to end up with a young girl in the three week period of high viremia. So this pattern is pretty dangerous. Have you thought along those lines besides prevention?

DR. COHEN: Yes. We've thought a lot about it. So the first issue is the older men/younger women thing bears fruit in a variety of ways. The younger woman often has an exuberant cervix, so there's more surface area. The younger woman often has vaginal flora that offers less innate resistance to infection. There is a lot of biological beggars putting a young woman at a disadvantage.

But in addition, the chance of running into an infected person would increase if you did it with an older man and just as you've said. So in South Africa where we're pretty sure that it's not older men infecting younger women, it's not that grazing phenomenon, where it's much more complicated, but in Tanzania you might have an infected person who believes it's an advantage to his own health to have sex with an uninfected virgin and the more years that man has been sexually active, the higher the probability he is infected. So you're increasing the kind of hits of a molecule just as you've said.

Okay. So this is one other way we've looked this and now I'm just going to end up a little bit on prevention just with a couple of things that I think probably are relevant to your committee. These are all the prevention strategies going on on this planet that I'm aware of and I would welcome Bob who is my kind of gadfly, I want you to look at this slide because you'll always some butterfly.

This ABC, STD interventions and there are still trials ongoing. The most powerful trials that are being done are the HSV-2 interruption trials, trials to try and prevent HSV-2 transmission or HSV-2 acquisition and I can tell you more about those trials if you want. Vaccine trials, there's a bunch ongoing, but I guess it's important B- Well, I'll say something about that in a second. Bacterial vaginosis, there are no trials ongoing. Microbicides, there are many trials ongoing. A very important diaphragm is ongoing. The male circumcision trials, there are three ongoing. One was stopped. Antiviral therapy trials, there are several ongoing using antiretroviral transmission event. Incentive for safer sex, we're not really doing trials, but there's a lot of thought about how societies might approach this problem.

By way of disclosure, I should say that I'm chair of a Gates Committee which is actually going to have temerity. So this is interesting. So I'll just slow down for a second. Gates realizes as it's invested its money its distorted research. Because every time it decides to do something in research that thing becomes important even if the thing is not important and these decisions are made by single individuals. So one issue is what have been the effects of Gates on the whole research portfolio. Have they done a favor or have they actually damaged the research portfolio? I don't want to say it that harshly but it's an issue.

The second issue is truth in advertising. What are we really going to do in the next 20 years and who has the courage to tell you the truth about what's really going to happen? And if it does happen, how important is it really going to be? For example, are we going to make a preventive vaccine in the next 20 years? Bob, is there any way on earth?

MEMBER REDFIELD: It's successfully B- distributed B-

DR. COHEN: I mean even we don't have the capacity right now. Any vaccine that's being tested is not a vaccine to prevent HIV infection. It's a vaccine to lower set point. That's all we're trying to do right now. But no one wants to tell the public that. It's like kind of an anathema to tell the truth. So instead we just keep doing this stuff and pretend like we're not doing it.

Diaphragm trials. There is a diaphragm trial almost complete. If the diaphragms work to prevent HIV transmission, that's a huge finding with immediate impact because that's just a little piece of plastic over the endocervix. The circumcision trials, those will be done this year. So we're trying to make a molecular clock. We're trying to say with the Gates Foundation how have you distorted research, what research is going to be done, when is it going to be done and what are the possibilities of the outcomes and how powerful could the outcomes be and I think that will be an interesting committee. That committee is just meeting this year.

Having said that we can't make an HIV vaccine that's preventive, I need to introduce you to an organization that you might not be familiar with that I'm one of the leaders of and that's called the CHAVI, the Center for HIV Vaccine Immunology. So recognizing, the NIH recognizing we weren't really making a preventive vaccine, they made a giant award, $300 million and the purpose of the $300 million for the CHAVI is to try to help us to enable development of a vaccine, to start over essentially and say what do we need to know to make a vaccine, why have we failed, where are we right now and why have we failed, not to make a vaccine, not to test a vaccine, but to do the science necessary to develop a vaccine properly.

So these are the kinds of things we need, subjects with acute infection for longitudinal studies, large numbers of transmission pairs, the infected person and the person who got the infection, HIV exposed and uninfected subjects. Who are HIV exposed and uninfected subjects? Do they really exist on this planet or is this another one of the big lies that we might be subjected to? What about genetics? We only have just tiny scratched the surface.

So the CHAVI has enough money to do the entire genome for very large numbers of people. So there is 30,000 snips in the human genome. We have enough money to do 30,000 snips of a very large number of exposed uninfected subjects and then there's studying mucosal samples in much greater understanding and depth than has been done before. So the CHAVI is worth knowing about, the NIH Center for HIV Vaccine Immunology. The leader is a guy named Bart Haynes. The principal investigator is Bart Haynes.

And lastly antiviral therapy to prevent transmission. Bob Bollinger and I have been working on this and many of us in this room have worked on this for a very long time. We do know how to make antiviral drugs. This came up already and there are three ways you could use antiviral drugs to prevent transmission. You could do post exposure prophylaxis which we're going to do whether it works or not because we have guidelines. You could do pre exposure prophylaxis with a pill or pills and there are randomized trials ongoing right now to test whether a pill before sex can prevent HIV acquisition.

And lastly the most important question is when the person is HIV infected takes their pills are they rendered less contagious and if so, how long are they less contagious and can we develop drugs for this purpose much as we've tried to do in the tuberculosis field. Over the next 20 years, can we actually focus on not just treatment for the sake of improving the health of the host, but also treatment for the sake of public health.

In summary, we can measure the concentration of drugs in general secretions and what's important about this is not all the drugs get in the same. So when you make a therapeutic decision, the therapeutic decision might be good for the host, but you might actually be giving the host a drug that actually renders them more likely to develop a resistant virus. So over the next few years, we expect physicians of drug companies to be more sensitive to this. This has to do with B- And Joe, you're giving me that confused look.

This has to do with compartmentization. Protease inhibitors don't get into semen or female genital secretions. They are too highly protein bound. So if you use a protease inhibitor alone you would be giving a subtherapeutic concentration to that compartment. So we always use combinations, but some of these drugs actually concentrate in the genital secretions. This is constant percent greater than blood in genital secretions, here the male genital tract.

There have been 14 studies looking at the effects of B-

MEMBER REDFIELD: Could you just go back for one second because if I see that slide just to point out that the most common regime used in the world would then be d4T nevirapine and 3TC.

DR. COHEN: d4T very poor penetration.

MEMBER REDFIELD: Nevirapine.

DR. COHEN: Yeah, very poor penetration.

MEMBER REDFIELD: And 3TC.

DR. COHEN: Excellent.

MEMBER REDFIELD: So you would argue that if we were doing that that this could B-

DR. COHEN: It's probably not the best public health. Right.

MEMBER REDFIELD: But this is the regime that's probably used around the world.

DR. COHEN: I understand but this is an unpublished slide. This is an article coming out in the Annuls of Internal Medicine. But again, I'm giving you where we are in research right now today. But your point is well taken and obviously prefer tenofovir, 3TC, FTC that they be used for all regimes for prevention, that they be included in all regimes especially for post exposure prophylaxis in the emergency room. We're trying to get the CDC right now to go back to their guidelines and say the guidelines ought to focus on some drugs and they ought to focus on some drugs because of drugs that get into the genital secretions.

MEMBER REZNIK: I'd like to say we actually brought that up yesterday as a point when we had a person here from Gilead.

DR. COHEN: Good. Who was here from Gilead? Jim Rooney?

MEMBER REZNIK: Jim B-

MEMBER YOGEV: Nevirapine you cannot say is not very poor.

DR. COHEN: No.

MEMBER YOGEV: It has a very good track record.

DR. COHEN: It's comparable in general secretions to blood. It's not poor. He said it. I didn't say it.

MEMBER YOGEV: Okay.

DR. COHEN: He's saying it has 70 percent there.

MEMBER YOGEV: Yes, and I was wondering where you got your data on the efavirenz because there is some data to suggest that it's as good as nevirapine and it's fascinating. It's the only one which you have a three percent and that it's almost the same molecules. So I'm wondering where that for efavirenz is coming from.

DR. COHEN: You know I would have to break apart. There is a lot of data that goes into this slide. This is a summary slide. So I can send you the raw data. If you send me an email, I can send you the raw data.

MEMBER YOGEV: Please.

DR. COHEN: Angela Kashuba, K-A-S-H-U-B-A.

MEMBER YOGEV: Because efavirenz as you know now is one of the considerations to go into because of liver disease in multiple studies and it would be very important to have it.

DR. COHEN: Of course. I do understand that. Combivir and efavirenz is what we're using for B- Actually you've raised a good point. So let me just show you. If you take semen and if you go before therapy and after therapy, before therapy you can easily detect HIV in semen. After therapy, you have trouble detecting HIV in semen. You can still detect HIV DNA in semen and as I've said, some of the drugs concentrate in semen and they can also concentrate in female genital secretions.

We're doing a study for seven years called HPTN 052 designed to determine w