Hope and Hype: Reports from the Front Line of New Anti-HIV Combination Therapies
by Darien Taylor
Over the past year or so, key advances in HIV research have changed our understanding of the management, and possibly the outcomes, of HIV disease. Three protease inhibitors, saquinavir, indinavir and ritonavir, are now widely available in Canada, and promising new anti-HIV drugs are in development. Viral load testing, which measures the amount of virus present in the blood, is also recently available in Ontario. Protease inhibitors, used in combination with other antivirals, are proving to be extremely effective at reducing viral load, in many cases below levels detectable by current viral load technology. And significantly reducing your viral load probably means that you will live longer and healthier, and will not become resistant as rapidly to the drugs that you are taking.
So far, so good.
But how do these advances in HIV research and clinical management of HIV play out in terms of the experience of people living with HIV? Protease inhibitors are costly, not easy to take, and tend to cause fairly nasty short term side effects, not to mention their long term toll on the liver, kidneys, and other internal organs.
The following reports from people who are using combination therapies are an attempt to get beyond the numbers: the fluctuations in CD4 counts and viral loads, and to look at the social and psychological implications of this “post-protease” moment : the hope, the expectations, the caution, the confusion, and also the practicalities and “lived experience” of these drug regimes.
1. Laurette
Diagnosed in 1995 but infected in 1985. Forty years old.
Doing AZT/3TC/ saquinavir.
Viral load pre-therapy: 596,000
Viral load 6 months into therapy: undetectable
“I have always been interested in caring for my body as a whole, using homeopathic and natural remedies, rather than chemical drugs... So after my diagnosis it was natural for me to become increasingly interested in an approach favoring vitamins and supplements, and in following the advice of my Traditional Chinese Medicine doctor. I started to visit a homeopath/ naturopath regularly. I was healthy, working, and had lots of energy. At that time, I refused to take any drugs.
I had to stop working when my CD4s were around 200. I was toying with the idea of starting to take Septra to prevent PCP. This was going to be my first AIDS drug and I was delaying making the decision. But then I had a painful episode of shingles, during which PCP was detected, and my life changed. I became a person living with AIDS. I was taking naps during the day, on top of ten to twelve hours of sleep at night, and I couldn't predict what I was going to be able to do the next day.
Six months after my PCP diagnosis, my CD4s had dropped to 117. I was scared of getting really ill. Following my doctors’ advice, I started to take AZT and 3TC. After four months of difficult decision-making, I decided to take saquinavir as well.
How did I reach this decision? Lots of talking. With friends who were not taking drugs and with friends who were. People who were already taking combination therapy encouraged me to start: they were really feeling better. Lots of reading. Endlessly tossing around my ideas with my HIV- friends and with my partner. Going to all the meetings in town where doctors reported back from various AIDS conferences.
Now on top of twenty vitamins and supplements per day, I am taking fifteen new pills. My medications must be taken with food, and the saquinavir with grapefruit juice, three times a day, eight hours apart. Ideally I get up at 7 am., take my meds with breakfast and juice, then again at 3 pm. with some food and juice, and again at 11 pm., with some food and juice. Imagine! Before, I always tried to eat two hours before going to bed, I never drank sweet juices and especially not with food. Now when I leave home, I need my little pill box, my container of juice, and a snack.
So that's my routine: a very structured day. Obviously, my timing is rarely eight hours on the dot. After a while, you realize that you just do your best. You don't panic if you are an hour off.
The first months on combination therapy were very uncomfortable, and even after six months I am still dealing with side effects: bloated belly (I don't fit into some clothes anymore!), constant gas, daily nausea. Every day I take herbal remedies to clean my liver and kidneys which are weakened by these drugs.
But in exchange for all this I have my energy back, all my HIV-related symptoms are gone, my CD4s are around 300, and my viral load went from 596,000 in January last year, to undetectable after 6 months of therapy.
I do not feel that my philosophy of health has changed. I wanted to do everything possible to recover a normal life.
2. Robert
Probably infected between 1981 and 1983.
Using saquinavir and ritonavir in addition to other antivirals.
“For a long time I was quite certain I would never get sick. My CD4 cells stayed up in the 500s and I felt in good health, apart from bouts of thrush and leukoplakia. I developed persistent sinusitis which is quite debilitating and which my doctor thinks is HIV-related. I like that explanation because it means that I don't have to give up smoking.
In 1993 my CD4s fell below 400. They kept falling. When they got to the mid 200s, my doctor and I finally capitulated, and he wrote me a prescription for AZT. That was more difficult than finding out that I was HIV positive because it made the illness real. But at the same time, I still felt well, and had no sense of being infected with a terminal illness.
I had a curious double vision when I looked into the future. On the one hand I though that I would get through this even while all around me people were dying (including two ex-lovers). On the other, my own sickness and death seemed simply a matter of time.
By 1995 my CD4s had fallen to 60 and HIV seemed impervious to antiviral therapy. I stopped buying RRSPs and started planning who to leave money to.
Now combination therapy has turned everything around. Ritonavir and saquinavir have reduced my viral load to the undetectable level, though my CD4s go up and down. I have still never felt sick. But pill time is a major organizing factor of my day, and until a few months ago, the side effects of ritonavir were interfering in a big way.
I felt a bit detached when my viral load came back undetectable, as if this were too good to be true. Coping with HIV now means being cautious and hopeful at the same time. I get inspiration from other HIV positive people in this regard, as well as from my doctor, whose levelheaded view of HIV has helped me feel more on top of things in these last ten years than not. But then, maybe I'm just a sucker for an authority figure!”
3. Bruce
48 year old gay man. First diagnosed in 1985. Did AZT monotherapy for several years, then AZT and ddC, then AZT and 3TC. First viral load test, done in early 1996, was 317,000. Switched therapy to AZT/ 3TC/ saquinavir. Second and third viral load tests were between 1,800 and 5,000. Changed therapy to 3TC/ D4T/ indinavir. Viral load now undetectable.
“Mine is an HIV success story. I first developed symptoms of HIV (swollen lymph nodes and weight loss) back in 1984. HIV was a death sentence then. In fact, in 1985, I was incorrectly diagnosed with cryptosporidium and told that I had six months to two years to live! That was 12 years ago!
I went on combination therapy, AZT and ddC, back when nobody was doing it. My doctor thought I was crazy. I read everything I could on HIV and I went to a buyers’ club in Florida with my mother to buy the ddC, sweating it out at the border coming back. It was like: “Do you want to live or not? Are you going to do everything possible make sure you live?” If the answer is yes, then taking the drugs, their side effects, compliance, are all easy issues.
For me the side effects of my current regime haven't been too bad. There's some fatigue; they leave a bad taste in my mouth. What is difficult is wondering, hoping the blood work results will last, the uncertainty of “crashing”, the big “what ifs”. Even though I'm doing well now, I worry about being “left behind”, the moment when the drugs work for others but not for me. It ain’t over yet.”
4. Greg
Diagnosed in 1990 but probably infected in the early 1980s. Worked as a clinician with people with HIV since the beginning of the 1980s and in the 1990s has worked mostly in HIV research.
“I'm terribly optimistic about the combination of drugs that I'm on: AZT/ddI/3TC/saquinavir soft gel cap. I want to believe in science or I wouldn't be doing what I'm doing. At the same time, I'm fearful of believing in that hope and at times feel like I'm waiting for a doomsday scenario to open before my eyes.
I didn't truly understand the ramifications of the decisions I was making when I started treatment. I feel somewhat trapped and cornered at this point. The scheduling of drugs seems virtually impossible to do in my everyday life. However, life becomes so regimented around a schedule when you're on fasting drugs, like ddI, and drugs which you have to take with food, like saquinavir. I take drugs at different points six times a day, and it brings up a lot of social issues that I hadn't thought about before. The gastrointestinal side effects are also significant but I just try to ignore them and get on with my life, and that usually works.
The most annoying thing for me is having to eat something substantial in the morning. I was always a light breakfast eater. I feel like it will be impossible for me to do this forever. You can't keep it up.
One of the things that I think we are instilling upon ourselves within the community is a sense of guilt if you don't get on the bandwagon and take these new drugs. We're, to a certain extent, erring on the side of forcing people to take these drugs. And then after they're on the drugs, they're finding out what the side effects are, the ramifications on their daily lives, which isn't a good time to discover these issues.
There are also questions like, “What will this do to my ability to move in and out of the work force if I ever have to? What if I want to change jobs and I'm on these drugs and I need the insurance coverage, and it's unlikely I’ll ever be covered again? What if public health wants me to take these drugs, since when I'm on these drugs I'm not secreting this virus any longer?” And questions about survivor guilt: “What if I live when all my friends took these drugs, tested the new ones, but died before me?”
These are issues I hadn't thought about until the Vancouver AIDS Conference last year. I came back very bewildered. I felt very low because I realized then how I had prepared myself to die of AIDS. I was comfortable with what I thought was inevitable. All of a sudden I was being offered a chance, and I wasn't sure that I wanted it. I was very conflicted. I started to look at all the things in my life that were going to be affected by taking these drugs and living longer. Pretty strange feelings for someone who really wants to live.
I have always believed in combination antiviral treatments. But you make your decisions with incomplete information about what the resistance patterns are, what drugs you'll be able to switch to later, which ones you'll have cut yourself off from. But you've got to make those decisions. You have to be willing to let go a little and say, I’ll make the best decision I can based on what I know. And then you have to let it go. You can't know everything you need to know and you can't predict the future.
In addition to lack of information, there's also information overload. I try to say that on Sunday afternoon between 2 and 4, I’ll hit the Net. But you get overloaded with all the garbage floating around. I really feel that I've hit the wall as to how much information I can take in personally.
5. Darien
Diagnosed with HIV in 1986. Probably infected a year or so before diagnosis.
Current combination: D4T/ 3TC/ saquinavir/ ritonavir
Pre-therapy viral load: 120,000
Current viral load: Undetectable
I've known that I'm HIV positive for more than ten years now. I've had no symptoms of HIV whatsoever. Which is a bit of a mind-fuck. On the one hand, you know that you have this dreadful disease, and on the other hand you feel physically quite normal. Of course, medical technology tells me that all is not exactly normal: blood tests, lab forms, lab slips, etc. But basically, I've felt well and my CD4s have stood up well under the strain.
I started on drugs after the Vancouver AIDS conference last July. My CD4s had dropped slightly, but mostly I just felt it was time to start drugs. Things seemed promising. I started with a pretty conservative combination: AZT/ 3TC/ ddI, thinking that since I’d been well for so long that I probably had a low viral load to start out with. And viral load testing wasn't available in Ontario then, so I just had to call it myself.
Well. obviously I was wrong. When my viral load test came back in January at 120,000, I was pretty surprised. So now I've just started on this new combination: AZT/ D4T/ saquinavir/ ritonavir. I have a numb mouth, tingly hands, flushing, and some euphoria. Gas, diarrhea, fatigue. It's been rough, but I'm feeling much better now that I've decreased my ritonavir dosage from 600 mg. twice a day to 400 mg. twice a day. In a strange way these side effects confirm for me what I've known for a long time... that I have HIV. They give me a physical, embodied correlative of my disease.
The ritonavir/ saquinavir regime is pretty easy to follow because it's twice a day with food. I have a hard time doing fasting drugs because I used to have an eating disorder and having to fast reminded me a lot of that. I have a difficult time “self-regulating”. So I really want this combination to work for me.
Coming back from the Vancouver AIDS Conference, I was quite depressed. Part of it was knowing that I had to reformulate my life around the hope that was being introduced into the lives of people with HIV. I was very reluctant to do that. After all that work preparing myself to die, I was too tired to take up the idea of hope at that time.
All my fantasies, all my preconceptions about HIV and my future got turned around in a way that was completely unpredictable. For me, part of coming to terms with living with HIV had been understanding how my life would unfold with this disease. And 1996, with the Washington conference and then the Vancouver AIDS conference, turned everything upside down. And at that time I thought, I'm not going to spend any more time constructing what my life may be like with HIV. I can't predict it. I could live. I could die. I could be disappointed. So giving up these fantasies of control, of “knowing” the outcome, replacing all that with a big shrug, has made me able to do things I couldn't do in the past. So here we are, a few months later, and I've done a number of things I never expected I’d do, like buying my house, and applying to go back to school. It's been great. I've been very happy, and the euphorics of ritonavir only add to it.
I was surprised at how unaffected I was when I got back my first viral load result, the high one. I put down the phone and I thought, “Well, I wonder how many nights this is going to keep me awake?” But it didn’t. I thought, “There's fuck all I can do about the number I've just received, and lots I can do to change that number.” I didn’t think about it and it hasn't bothered me much. And now my viral load is undetectable, which I’d pretty much expected, and the side effects of my combination seem to be leveling off.
6. John
Diagnosed with HIV March 1994. First viral load test, June 1996: 8,000. Six months later, in September, viral load was 700,000. The following month, started d4T/ 3TC/ saquinavir/ ritonavir. December 1996, viral load undetectable.
“I tried to build up my ritonavir dose to 600 mg. twice a day over two weeks but I could only tolerate this dose for a few days. I experienced chronic diarrhea, mild nausea, felt badly tired and “out of sorts”. My doctor was follow Dr. Bill Cameron's study of ritonavir and saquinavir, which was showing a negligible difference between the 600 and 400 mg. doses, so we agreed to drop back to 400 mgs. This was a big relief!
When my December 1996 viral load was below 500, I was very happy, amazed in fact! I continued to have periodic, but not debilitating diarrhea, which was exacerbated by alcohol consumption. I found it hard to lay off the booze over the Christmas/ New Years period, so this did contribute to the diarrhea. I also experienced profound numbness and tingling around the mouth and “speediness” following my morning dose, usually peaking around lunch time I found this aggravating and unsettling but have gradually become accustomed to it. Also occasional insomnia.
In January, I had a major disagreement with my doctor. He showed me data which I found difficult to understand suggesting that the “effective concentration” of saquinavir/ ritonavir was optimal at the 600 mg. twice daily dose. He suggested that I should increase my dose. This threw me into a spin and led to a major “gloves off” discussion about the limits of his knowledge and his capacity to be “up with the literature”, compared to my expectations of him as my advisor. We had very frank and unpleasant discussions about his authority as a doctor, including discussion about the possibility of me seeing another doctor. My partner, who works in a community-based AIDS organization, helped me to conclude that I would stay on 400 mgs. twice daily for the time being.
Overall, I am very content with my current regimen. After six months, nearly all the side effects have disappeared, although the diarrhea does recur after alcohol consumption. I feel perfectly normal again and am fairly confident about my ability to adhere to the protocol. Taking pills at 12 hour intervals remains a pain in the bum, especially as I am now not working (not due to health reasons) and therefore lack a regular routine. I try to get up with my partner and eat breakfast with him at 8 or 9 am. His support is as invaluable as his constant reminders to take my pills can be irritating. My satisfaction is tempered by the fact that I have only been on this regimen for a short time. Optimism must be weighed with caution.
But I have become skeptical about the capacity of some HIV general practitioners to stay abreast of current medical knowledge about the treatment of HIV. Also, I do not enjoy riding the viral load roller coaster every three months as I await the outcome of my blood test results. I think that the psychological impact of viral load monitoring is underestimated. The important thing is to try not to panic, to accept that viral levels can fluctuate, and to maintain a broad perspective on your results rather than panicking about individual test results.
I have detected a new form of rivalry as some people with HIV seek to persuade others that the combination that they are on is better than the one being taken by the person to whom they are talking. More discussion is required to assist people to feel confident about their choices and to establish an etiquette which would enable people with HIV to discuss and compare combinations and viral load levels compassionately, without being competitive or causing offense.
I have been gradually and continually reassessing my future and am more optimistic than I was about my prognosis. However uncertainty has by no means been eradicated. The long term durability of the efficacy of combination therapy and the long term side effects remain of considerable concern. I swallow and hope like hell!
The possibility of undetectable viral load being linked to reduced “infectivity” gives rise to the prospect of renegotiating sexual practices and condom use with my HIV-negative partner. This “advantage” is countered by the very difficult and shifting assessments of what constitutes “risk” in the age of combination therapies, compared to what we have come to believe is acceptable risk over the past decade or so. The prospect of reassessing sexual risk- taking opens the lid on a number of community taboos, challenges norms, and places both me and my partner at risk of incurring the community's wrath if we discuss openly what we are doing and thinking. This opens up a whole new set of fears and anxieties.
My natural desire to stay informed about treatments, new developments, clinical trial results and anecdotal evidence is challenged occasionally by pressure to shut up, be a good boy, take my pills, and not ask any questions.
