The Multi-Centered AIDS Cohort Study (MACS) Experience

In 1985 I was one of the first people ever tested for HIV. Since then millions of people have visited clinics and testing centers around the world to find out their status. Before that you couldn’t get tested for HIV – there were no testing centers. The HIV antibody test had just been developed. But I didn’t need to get a test. Scientists already had dozens of vials of my blood stored away since April 1984.

I am 40623 - the 623rd participant enrolled at the fourth MACS study site – UCLA. “MACS” stands for Multi-Centered Aids Cohort Study, the largest and longest running study in the world about how HIV is transmitted from one person to another and how it progresses in the body and the brain. Much of what we know today about HIV disease we learned from the MACS study. It began in 1984 when the US National Institutes of Health (NIH) enrolled over 5,500 volunteer participants at four university sites – Johns Hopkins University in Baltimore, University of Pittsburg in Pennsylvania, North Western University in Chicago, and the University of California at Los Angeles, UCLA. I was part of the UCLA cohort – number 623 of the eventual more than twelve hundred men who joined the LA Men’s Study – “LAMS” for short. The MACS study is also known as “The Natural History of Aids Study”. Sometimes I joke that MACS was the study so great they had to name it three times. Certainly, like the Energizer bunny, it keeps running and running and.… years later we are still learning more about this disease.

My research to publish an abstract about aspirin and HIV at the Amsterdam AIDS Conference in 1992 

When the MACS started in 1984 scientists knew very little about HIV or Aids. Researchers had determined that Aids is caused by a retrovirus although they were still debating what to call it. To help fill in the huge blank in our scientific knowledge the largest medical research institute in the world, the NIH in Bethesda, Maryland instituted a broad, deeply based study to try to determine as much as possible about this emerging disease. How does the virus pass from one person to another and what happens in the body once a person has been infected? How fast does all this happen? Over one thousand medical journal papers have been published based on data gathered by this massive study and the numerous sub-studies it has spawned. More than thirty years after it started recruiting participants, the MACS study is still going strong.

After reading a small article in one of the local West Hollywood newspapers requesting volunteers, I called and made an appointment to come speak to someone about signing up. I drove to the LAMS site in West Los Angeles for my interview and after finding out more about the study and what was required, I immediately signed up. The UCLA arm of the study was recruiting men in Los Angeles who might be HIV positive or who were in a high risk group. In 1984 there was no test no one knew if they were positive or negative or how prevalent the disease might be. I thought I had probably been infected the previous year when I had become extremely ill with severe flu-like symptoms but I wasn’t absolutely sure. Maybe I had managed to dodge the virion. Maybe that serious flu was just the flu. Besides, I figured if I did turn out to be positive, by participating in this study, it would put me in touch with the most up-to-date science available. If there was any way to live through the Aids Crisis when so many people in Los Angeles were beginning to get sick or dying, the MACS study would be it. By participating I could be totally plugged into the emerging science. If it turned out I was negative, at least I would be contributing to the advancement of science and perhaps eventually even to a cure for Aids. If I was going to volunteer for anything it might as well be something that might help my community, country and the world overcome this disease that had suddenly emerged killing people in the prime of their lives. In the mid-1980s Aids was already being compared to the greatest plagues of history. No one could predict how big it might become or how long this new plague might last – how many it would kill or where those deaths might be. In 1987 I went into the Washington DC, Capitol Hill office of a Republican Member of Congress from Indiana. In the entrance to his office a large chart projecting that Aids would kill forty million Americans by 2000. There was a scare in the air. Some suggested quarantining everyone who tested positive or maybe put them all on an island. No one said who would pay. Faced with this I wanted to do whatever I could to contribute to ending this monumental problem confronting mankind. By donating my blood and my time to the study I felt I was doing my part. Plus I might even enjoy a real trip through science that might save my life. It looked like a win-win situation.

The University of California at Los Angeles has one of only two officially designated Aids Institutes in the United States. The other is at Harvard University in Boston. UCLA is a good place if you want to be plugged into science. In the late 1990’s I served for three years on the Community Advisory Board (CAB) of the UCLA Aids Institute. It met monthly to review clinical trial research protocols for safety issues. The CAB was supposed to give feedback to the scientists about what people in the HIV community would think about the design of those trials - and on the other hand, help inform people with HIV about the possibility of participating in these important trials. Attending almost every committee meeting for three years was certainly interesting…. but I didn’t get a huge amount of personal satisfaction out of it. But being part of the MACS study was fascinating – even inspirational.

When I joined the study in April 1984 I agreed to visit the MACS clinic site twice a year. It was located in the basement of a non-descript medical building across from the Veteran’s Administration complex on Wilshire Boulevard in West LA. Several months after I joined, the MACS administrator asked if I would like to up my ante. I agreed to come in for an interview and blood draw every three months instead of just twice a year as I had originally agreed. So twice a year in the Los Angeles morning rush hour I guided my older model BMW westward from my residence just off the Sunset Strip in West Hollywood, down Santa Monica and Wilshire Boulevards through Beverly Hills towards the medical building in West LA for the full two hour poke and test interview session. Then twice a year I’d also go just for a quick physical exam and blood-draw that would only take half an hour in and out. It had to be the same 8:30 time slot each time because immune system indicators in the blood vary a bit depending on the time of day. The routine of a MACS visit never varied.

Turning off Wilshire I parked the aging Beamer in the lot, walked through the automatic glass doors to the building and descended a flight of stairs to the basement. Two doors down the corridor on the right a discrete sign announced - Los Angeles Men’s Study. As I entered the receptionist Dennis unfailingly welcomed me with the same greeting, “Oh, Howard, you’re here! Here, just fill out this form. Great to see you.” I filled in my contact information and relaxed with a magazine in the reception room for a minute. Sitting on the couch I penciled in the ovals on the psychological questionnaire about my level of joy or depression. “No - I don’t have low self-esteem.” “Yes - I think I’m as good as anyone else.” When called I handed in my responses and walked the twelve paces over to the poking room. There I had to give up my blood - usually eight small vials but sometimes ten or twelve – deep, red and rich. I disrobed, was tape measured, weighed, had my hands and feet examined, some body thumping, and finally the prostate examination – a truly probing experience. With the poking completed I put my clothes back on and was rewarded with a six ounce juice to replenish my fluids and an option of cheese crackers or sugary biscuits. I choose both. Next came the interview session. Twenty feet down the hallway in the small interview room the professional staff member asked the exact same questions every time – the petit Grand Inquisition. What alcohol have you consumed? What drugs – legal or illegal – have you taken? How often and how much? What sex have you had? If you did have sex, precisely what did you do? Who put what where and how deeply? Then came the manual dexterity test, putting small off-shaped pegs into matching odd-shaped holes - for sixty seconds. First with my right hand and then my left. Next…. three or four memory tests – I forget. My memory was good. In the first three years participants had to give a seamen sample. Not anymore. Finally there was a computerized reaction-time test – tapping at the computer keyboard space bar as soon as the same letter or sequence, ascending or descending, was flashed for a millisecond on the screen. After two hours of questionnaires, poking, reaction time tests and computer tapping, I received a free pen, note pad, parking validation and petrol money and could finally make my way through the late morning traffic back to West Hollywood. Each MACS visit was a small contribution to the glory of science and the war against Aids. Like clockwork, twelve days after each site visit I could pick up my blood test results from my 90069 West Hollywood post office box – the one I held for the Project for Aspirin Research (PARE) or the International Project for Affordable Therapy for HIV (IPATH). They were the front organizations I established to help promote my efforts to marshal practical science to help both Africans and Americans improve the way they treated HIV. When the results letter from MACS indicated not only my CD4, CD8, CD4/CD8 ratios and viral load numbers, but also my CD38 number, plus all the other standard laboratory blood tests. It gave me my complete results. Just as the Weekly Reader had forecast when I was in elementary school in the 1960s, I was using biofeedback to improve my life and health. It felt like the future of medical science had arrived.

When scientists finally developed the test for HIV in 1985, the 5000 plus participants in the MACS study were some of the first people in the world to get their results. The National Institutes of Health (NIH) sponsored study with its cadre of scientists at four major university medical schools were among the first to access the newly developed antibody test kits. MACS went back and tested everyone’s blood they had stored from the time they had entered the study – mine from April 1984. On my next MACS visit when the study coordinator called me into the private interview room she asked me if I wanted to know the results of my test. Of course I did. She calmly but frankly explained, “Your blood tested positive and the blood we have stored from April 1984 when you first entered the study is also positive. "As you know, currently there are no drugs to treat this disease - and we may never have a drug to treat HIV since we have never had a drug that can treat a retrovirus.”

I accepted the news without any fear or disappointment. I had expected that news for some time and had already made my psychological adjustments. Now I just had to make the most of it. My father had died at the age of thirty-nine when I was not quite six. I was thirty-three. I figured I had maybe five years to live – plus or minus. Maybe I could live to be thirty-nine like my dear father, or maybe live to see 1990. The one thing I knew was that I needed to change my life somehow. I needed to change direction…. somehow. I wanted to contribute to my community, especially to do something to help other people with Aids. But I didn’t know what and I didn’t know how. Maybe I would figure out something in time. The thing to do at that moment was to get on with my life and not stress over the situation. Why bother? It wouldn’t make any difference. I had to face facts. There was nothing I could do - so why worry? Everybody has to die sometime. But somehow, I wanted to help.

Participating in the MACS study laid the foundation for me to become an Aids researcher. Today, thirty years after joining MACS I may be the leading autodidactic – completely self-taught - Aids researcher in the world. Los Angeles was one of the first epicenters of the Aids epidemic in America – LA, San Francisco, New York and Miami. It was a frightening but also an exciting time in the history of medicine and disease. Through a continuing commitment to study this disease through library and field research, I eventually converted a crisis in my life and the life of my community into an opportunity to help people - worldwide. To help people everywhere with HIV move further, faster towards a cure for this extraordinary disease whose burden has fallen on some societies in Africa like a ton of bricks.

I learned from “The Wizard of OZ” that you shouldn’t let a piece of paper hold you back from what you need or want to accomplish in life. I fell into the Aids game at the same time the “bona-fide” scientists did. I read all the research about this new disease directly from the scientific journals since the very beginning, just as the Aids professionals did. I attended most of the international Aids conferences they did. And I read several of the latest medical textbooks on virology and immunology, just like they had. The only thing I didn’t have was a PhD or a medical school MD behind my name – no bono fides – no meal ticket.

Although I didn’t have a research laboratory, I had my own body to conduct one-person case-study trials and self-experiments. For years I read hundreds and hundreds and more hundreds of medical journal articles – the latest science – and I learned how to pick out the flaws and mistakes that sometimes occur. It happens much more often than people think in emerging science. For a while I became expert on cytokines, the chemical messenger signals that cells in the immune system use to communicate with each other. Basically I learned what all the other scientists learned and knows. If you want to be taken seriously at an international scientific conference you really have to know what you are talking about.

However I examined questions of Aids science from a slightly different point of view. With a fresh and curious understanding of the facts I had learned from my extensive readings in virology and immunology. I used an analytical matrix of someone who has the disease and is participating in the research. I was curious to find out what questions were not being asked. What aspects of this condition were not being looked at? Where were the gaps in knowledge that were not being filled in by active research? What might have been covered up by who knows whom? And what key information may have been learned, but is now forgotten, lost in the shuffle of the biomedical industry’s rush to develop and improve modern ARV medications.

I knew from my readings in the history of medicine and science how often important discoveries have been made but because of the conservatism of the medical establishment they have been ignored, diminished, covered up or swept under the rug, only to be recognized years or even decades later for the brilliant advances they are. The list is extensive but it includes the use of vaccines, the importance of genetics and many more breakthroughs large and small that were not accepted – indeed ridiculed – when they were first put forward by serious doctors and scientists. In the history of medicine the list of these extremely significant but initially ignored discoveries is legend. After putting in my 10,000 hours of study and on-the-ground research, I evolved into an Aids scientist…. or as I often say, “a simple scientist.” Or perhaps call me an analyst who understands 99% of the complex science converging around immune deficiency diseases. Someone who can pick out the holes in bad science and point out the black holes in Aids research. I had no budget or financial sponsor for my research other than myself and that’s what scared the big boys more than anything. “Where did this guy come from?” ….Hawaii?

Through twenty-five years of research I’ve always tried to answer the most basic but often unasked questions. Most fundamental is the existential question of exactly how does the HIV virus cause Aids? In thirty years of monitoring the constantly advancing knowledge about this disease no one has fully outlined the chain of cause and effect that leads from initial infection to the eventual massive decline in CD4 cells that is the hallmark of this disease. In thirty years of going to Aids conferences I have only heard one scientist bold or perceptive enough to actually ask this untouchable question – the question that no one dares ask - “How Does HIV Cause Aids?” Dr David Ho, leader of the research team that first developed protease inhibitors posed that question or rather pointed it out in his keynote address to the First International “Scientific” Conference on Aids held in Buenos Aires, Argentina, June 2001. It was the twentieth anniversary of the discovery of the disease.

So just how does HIV cause the decline in CD4 count? How does HIV disease go from initial infection to cause the gradual decline in immune function until the body suffers the severe loss of CD4 cells up to twelve years later? Why has no one ever clearly and convincingly explained how and why that progression happens? More importantly - Why has no one ever even asked this question? Is the answer so horrible that all the Aids scientists run away from that question? Do they already know the answer? Are they hiding the answer? If so…. WHY? What gives?

No one else in the field has been brave enough to tackle this scientific question head on. This book attempts to outline a logical, scientifically based explanation even though it does not pretend to be a complete and final answer. The essay included here, “How HIV Causes Aids” points to where that answer lies.