In a little over four months I will turn fifty. When I was diagnosed with HIV in 1988 I never dreamed I'd reach forty. I've survived a long battle with HIV, and it has not been easy. It's taken a concentrated and impassioned effort to gain every piece of knowledge I could in order to stay ahead of this deadly virus, one that has a basic survival instinct not unlike my own.
HIV drugs have changed the course of the epidemic in a relatively short time and have played a huge role in my survival. In fact, my treatment history reflects the progress and pitfalls of AIDS research. Each step along the way I was as aggressive as possible in my treatment decisions. Over the past 18 years my virus first became resistant, then highly resistant, and now what we call "multi-drug resistant" (MDR). Doctors use the same terminology in tuberculosis -- usually signifying a serious condition, one that is difficult if not impossible to treat. In HIV, the condition is problematic not only because it becomes difficult to treat, but because MDR HIV can be transmitted to other people.
What I didn't realize when I began HIV treatment was that I was creating a recipe for disaster. The correct use of anti-HIV drugs had to be learned over time, and even though I was fortunate enough to gain access to new drugs almost as soon as they were discovered, I used them incorrectly. Each time I added a new drug to another older medication I was creating a more mutated virus. But, I was doing what anyone in my situation would do in order to survive.
For someone with MDR HIV, finding a new treatment today is just as complex as it ever was -- and for me, finding an effective drug combination has been a roller coaster of decision-making with considerable frustration. In some ways it's been like a long war waged against improbable foes. I have had to consult with many doctors, haggle with drug companies, sustain risk through several clinical trials, and even get arrested in actions of civil disobedience, all to get the drugs that have kept me alive.
Most drug studies offer me only what is known as monotherapy, since they provide only one new drug in addition to the backbone of drugs I am already resistant to. It's been the bane of my existence since the early days of my HIV treatment: trying to find two active drugs to work against my crafty and persistent virus. We know now that at least two active drugs are needed for the greatest control over HIV replication. But I learned this too late.
I first began treatment back in 1989 with AZT, the cause célébré of AIDS protests on Wall Street and at the FDA. I was one of many who started using it as monotherapy, thus starting my resistance cycle and mistaken treatment course of sequential monotherapy. But back then, it was all we had and we all demanded AZT.
After using AZT for several months I gained access to ddC (later approved as Hivid) from an AIDS buyers club (before it was available by prescription) and began my first dual regimen, not knowing that I was getting little, if any, benefit from ddC. I probably had already developed resistance to AZT, allowing mutations to occur and beginning my ride on the resistance roller coaster. Shortly after this, I developed my first opportunistic infection: extrapulmonary tuberculosis. I was scared to death and afraid new HIV drugs would never materialize.
I was successfully treated for tuberculosis and moved to San Francisco in order to be connected to cutting edge care and treatment. Over the next few years I tried a lot of complementary therapies and began switching to new drugs as they became available. I took Videx and then Zerit, adding each of them to whatever I was taking. So essentially I was building new mutations and using only one effective drug at a time. This went on for several years as I slowly watched my CD4 count drop.
I was one of the first people to gain access to Rescriptor (delavirdine), the first of the drug class called NNRTIs. But this turned out to be another big mistake. Later drugs in this class, Sustiva and Viramune, would be more potent and easier to take, but I needed Rescriptor then. What we didn't know at the time is that the drugs in the NNRTI class would be highly cross-resistant to each other. If you develop resistance to one, you blow the whole class. And I did.
I became very angry and frustrated at this time, and joined ACT UP, the AIDS activist organization. Many of us who needed new drugs planned very sophisticated actions targeting drug companies, the government, and sometimes even hospitals and medical institutions. Getting arrested appeased our anger by bucking the system and making some sort of stand against the status quo. As far as I was concerned the government and research institutions could never move fast enough when everyone was dying around you. We felt an incredible bonding as brothers and sisters fighting a war together to save our own lives.
By 1994 HIV was having an effect on my health. I was wasting (losing over 20 pounds), and beginning to develop other symptoms. I was afraid. Wasting zaps your energy, drains your confidence in surviving, and damages your self esteem. Skull-like faces and "AZT butt" (severe loss of the buttock muscles) were noticeable everywhere in the Castro district of San Francisco. One prominent doctor I was seeing at the time told me that I had no more options, that there was "nothing he could do" for me and my treatment situation. I fired him that day, not willing to tolerate his apathetic approach. I knew that HIV wasn't going to do me in . . . just yet.
A study of human growth hormone saved my life, despite the fact that I received the placebo for the first part of the trial. I regained my weight and enrolled in a study of the first protease inhibitor, Invirase (saquinavir). The background drugs in this study were AZT and ddC -- two drugs I had already used. So with Invirase as the only active drug in the regimen, I was once again taking virtual monotherapy. I had a lot of time to think about my health and my treatment situation as I made the hour-long drive to Stanford for each study visit. I once again found myself needing a new drug and entered a study of Crixivan. But it soon failed and my CD4 count slumped.
I had learned about research and the clinical trials process through my actual experience in trials and as a member of ACT UP Golden Gate. A group of us held an immune-based therapies "breakfast club" on Saturday mornings where we would pore over the latest journal articles and hear from graduate students and researchers from Stanford and UCSF. It led me to consider my treatment course a little differently. Up to this point every drug I had tried had failed and I realized I needed something to boost my weakened immune system.
So I joined a very progressive thymus transplantation study in hopes of restoring some thymus function, which plays an important role in the immune system. I was flown across the country to Vermont and underwent an overnight hospital stay as thymus tissue was transplanted to my abdomen. The thymus tissue was not rejected by my weakened immune system, but my CD4 count continued its slow decline. Still, I felt amazingly empowered with a renewed sense of living by participating in cutting-edge research.
For the next several years I remarkably maintained my health status while HIV research slowed. I tried other new protease inhibitors as they became available and began "recycling" my medications, reusing past drugs I was most certainly resistant to. I was technically on HAART (highly active antiretroviral therapy) but it would probably best have been described as "PAART," since it was only partially active for me.
In 2002 I enrolled in a trial of the first fusion inhibitor, T-20 (Fuzeon), after nagging investigators and the companies developing the drug (Roche and Trimeris) to get the study started. I was aggressive with the investigators as I knew this was a last chance of sorts, but my bad luck landed me into the arm that did not receive Fuzeon. Fortunately, the design of the study enabled me to receive Fuzeon after 24 weeks. After I started the drug my viral load went undetectable for the first time ever -- for just one week. I must admit I was thrilled yet skeptical. Since I knew I was resistant to my background regimen, Fuzeon was working alone and it was only a short time before my virus quickly developed resistance.
I still take Fuzeon, along with the newest protease inhibitor, Aptivus. These drugs plus Truvada have enabled me to stay relatively healthy, with the lowest viral load I ever had. Unfortunately, my CD4 count has dropped below 100. For me, all good things in HIV seem to end, so I now am seeking yet another new drug.
Recently, my options have gotten better thanks to a resurgence in HIV drug development. Several new drug classes are showing promise. And for the first time ever, a clinical trial is looking at two new drugs at the same time. The DUET study (see box on page 15) is looking at a combination of a new protease inhibitor (TMC 114) and an NNRTI (TMC-125) that are hopefully not cross-resistant to older drugs.
I was ready to jump into the DUET study and even screened for it. But then I met with several researchers and my doctor, and I realized that if I entered the trial, I would run the risk of getting the new protease inhibitor alone, since the trial randomized people into getting either one new active agent or two. They also felt that I most likely wouldn't get much bang out of the NNRTI anyway.
In addition, there are suddenly two very new drug classes on the horizon: integrase inhibitors and attachment inhibitors. This would afford me the option of adding them to TMC 114, and having two new drugs! But once again, because of all the drugs I have taken, the design of the integrase inhibitor studies will not allow me to have more than two new drugs that my virus has never seen.
So I've decided not to enroll in the DUET trial and will also forego the integrase study. I am in a holding pattern, buying time and waiting until I can access the integrase inhibitor though an early access program. By that time TMC 114 will hopefully be in the pharmacy and I'll have two new active agents. It's a tenuous position to be in, but I have little choice. I'm keeping my fingers crossed that I can maintain my health until then.
Hopefully, people starting HIV treatment today will not need to go through what I did, ending up with MDR virus and few options. The prospects are much better for choosing a regimen out of over 20 drugs that will be strong, safe and long-lasting. I think people with MDR virus should hold on as long as they can until they can gain access to at least two new drugs. Possibilities will open up for people who can wait. Sadly, there are those who can't.
It takes a lot of knowledge to follow what is happening to this tricky little virus called HIV. But people must be persistent and demand what they need. They should work closely with an experienced HIV doctor and know all their options. It can be done. I truly believe I am alive today not because of the mistakes I made in treatment choices, but because I was resilient, I fought back and was informed enough to buy time.
Survival can be a desperate thing. If you were stranded on a desert island, you would do whatever you had to stay alive. I think it is no different living with MDR HIV. Today, due to research breakthroughs, drug development, determination, patience, and awareness, a longer life with HIV is attainable. Maybe HIV finally is a chronic manageable disease.
Matt Sharp is Director of Treatment Education at TPAN in Chicago.