AIDS Is a Puzzle
9th Retrovirus Conference
The following is a summary of highlights from the 9th Conference on Retroviruses and Opportunistic Infections (CROI), which took place February 24-28, 2002 in Seattle.
The conference brought together nearly 3,500 of the world's scientists, researchers, clinicians, AIDS advocates, and the press. In addition to sharing relevant medical information from the conference, this article is also an attempt to shed a little light for the Women Alive Newsletter readers on what takes place at a scientific conference such as Retrovirus.
Most of the material presented comes from clinical studies conducted in the developed world (primarily the US and parts of Europe). There were however, many interesting studies presented from resource-poor continents, as well (like Africa, Asia, and Central/South America). Many countries are struggling to find ways to deal with the devastation that AIDS has caused, often without any government or financial support, and no means of activism which has been so successful here in the United States in terms of demanding that the government do the right thing which resulted in, among other major advancements, the receiving of financial aid such as the Ryan White Care Act Funding.
Tiny Rays of LightIt's disappointing that there wasn't any monumental scientific breakthroughs for this year's conference. However, there were many of what I consider to be "tiny rays of light" into our knowledge about HIV and it's treatment. In the broad spectrum of AIDS research, these little bits of information, which range from new ways to treat the side effects of antiretroviral therapy, to the study of immune responses in monkeys, all bring us a little bit closer to hopefully finding an end to this disease.
Before we look at what the scientists had to say, I thought it would be helpful to give a little background into the realm of AIDS research.
Puzzle PiecesWhen trying to understand the way that research is conducted (and why there isn't much "really big news"), it is helpful to look at it as a humongous jigsaw puzzle; a really BIG one, with 10,000 pieces or more.
When working a jigsaw puzzle, usually you assemble the border first, and then you can build inward toward the middle. Imagine that you and your friends are trying to put together a giant puzzle with thousands of "teenie weenie little pieces"; each one of you working on a different section at different times and in different locations. It is a difficult and slow process, but when you use the picture on the box as a guide, you can eventually begin to group the segments together and form the completed picture. This is kind of what the Retrovirus conference looks like -- lots of tiny little pieces to the big puzzle.
The problem with AIDS research is: There are no "pictures on the box" to follow, and needless to say, it is a very slow process.
The Same PuzzleAll over the world right now, there are hundreds of researchers looking at different aspects of the HIV/AIDS disease puzzle. Each one has his/her own specialty. Some of these individuals are scientists in laboratories looking under a microscope at the cellular or genetic pieces of the viral puzzle. Others may be working out in the field to test new ways of preventing transmission of HIV, (such as the perinatal transmission studies in Africa or the PEP -- post-exposure prophylaxis -- studies here in the US.) And still, there are countless others, who may be investigators in clinical trials like our own ACTG or CPCRA studies trying to find out the root cause of a particular complication such as Lipodystrophy, or the effect of a new HIV med on viral load. All of these people are working on the same puzzle.
What happens when one of these researchers finds a few pieces that fit together?
ConferencesThe Retrovirus conference is one of the places where all these different scientists can get together and share what they have learned about whatever part of the puzzle they have been working on. [That is the primary purpose of most all AIDS conferences including the National Women and HIV Conference.] Whether they found out something "good" in their study (like possible once-daily dosing for Kaletra -- abstract 409) or whether they found out something not so good (like HPV levels in the female genital tract do not necessarily improve if the woman is on HAART -- abstract 119), this is where they have the chance to show the results of their work. In order for a researcher to announce their accomplishment, they must present or publish their data ("data" is another word for information).
Abstract DataThe way that data gets presented at conferences is in the form of an "abstract." An abstract is typically a written document that gives a brief overview of the research that was conducted. It normally includes things such as the "hypothesis" of the study, (which is basically the idea that they had to begin with, and the answer that they thought they would find by conducting the study). In addition, they have to show their methods, or the steps they took to answer their question (such as, how many people did they enroll in the study, and what types of tests were performed). Finally, they include what the results (or conclusions) of the study were. Abstracts are submitted to conferences as a way for the researchers to share the information that they learned from their study (or experiment) with their colleagues and with the public. Most researchers do not, or cannot talk about their research results until they have been presented. When a researcher submits an abstract, they can present it in several ways. One is in the form of an oral presentation. This is where the researcher stands up in front of an audience and talks about their study using slides on a screen. Another format is called a poster session. A large poster is created with the information from the abstract and it is displayed in a large room with many other posters (usually grouped with posters of similar subjects). Certain times of the day are allotted for the authors of the abstract to be available at their poster to discuss it with conference attendees. There are also symposiums and plenary sessions (which are basically lectures on a specific topic), and on the last day of the conference the "Late Breakers" are presented. The term "Late Breaker" usually means that the researcher did not have all the data for their study ready when the original call for conference abstracts was due (which is months before the conference itself), but got it all together to present by the time the conference opened and requested to present it as a Late Breaker.
So now that you have had your briefing, I hope that the information from this year's Retrovirus conference will be helpful to you in your own search for knowledge. I encourage all people infected with HIV (especially women) to learn as much as they can in order to take charge of this disease in their own lives. It's not always easy to learn this stuff, especially if you're like me. And in most cases, most infected women are like me. We come from various backgrounds, but most often have experienced some other hardship such as drug addiction, homelessness, or oppression of some sort prior to us becoming HIV infected.
Do Your BestIn fact, it is quite a struggle for me to grasp some of the scientific concepts associated with learning about AIDS research. But I do my best, with the help of many friends and veteran community members, to absorb as much of the information as I can. Keep in mind, the best weapon we have against HIV is in our own will to overcome it. The more we learn and educate ourselves, the better we can "help our physician to help us."
After reading the following conference summary, if you would like to look at any of the data in more detail or to watch some of the plenary sessions on video, I encourage those who have access to log-on to the conference Web site at www.retroconference.org.
Women's IssuesAlthough there never seems to be enough data specific to women at any conference, there were a few interesting abstracts presented this year at Retrovirus, which caught my attention.
One study that is of particular interest to women with HIV was one that looked at the connection between PI use and decreased bone mineral density in women over the age of 35 (abstract 717-T, J.H. Arnsten). In this study, they looked at 40 women with an average age of 48. They had 19 HIV-positive women and 21 HIV-negative participants. In the study they analyzed the impact of protease inhibitor use on bone mineral density and found that PI use is independently associated with decreased bone density in older HIV-positive women. Note: There are several studies that have shown a correlation between HAART and bone loss in people with HIV, it is especially important to monitor this problem in HIV-positive women. A DXA (pronounced dexa) screening is a good test to detect decreased bone mineral density. Ask your doctor if you are concerned about this issue.
Another study that brought out an important issue for women was an oral abstract presentation on human papillomavirus (HPV) levels in the female genital tract. The study (abstract 119, L.J. Conley) took an issue that is already well known. The fact that HIV-positive women are at increased risk for cervical cancer related to co-infection with HPV, and looked at it a little further. They wanted to know if HAART therapy (meaning a combination of at least 3 HIV meds) has any effect on the HPV levels in the vaginal secretions of women. After performing a series of tests, they concluded that HAART did not affect the HPV levels, and therefore their findings stated that even women who are fully suppressed on medications, (meaning with undetectable viral loads) are still at high risk of getting cervical cancer, and should be screened just as frequently and thoroughly as women who are not on HAART.
There were a few studies that attempted to look at gender differences. One interesting presentation (abstract 777) was a retrospective study (meaning that they went back and looked at patients' charts over a period of time) done by Columbia University. They wanted to know if men and women who had similar T-cell counts when they started on meds got the same virologic response. They found these interesting points: first, women usually start meds with about the same T-cell count as men, but spend more time "just being observed" at the clinic before beginning therapy than men do. Once the women start meds, they have a better chance at becoming undetectable than the men in the study did. Once they were on stable therapy, they both maintained about the same T-cell and viral load responses.
Another study (abstract 775-W) did a retrospective review looking for gender differences in viral loads. Through a review of published data from the past seven to ten years, they found that women consistently had lower viral loads than men at similar stages of disease, in fact up to two- to six-fold lower viral loads than men, particularly early in HIV infection following seroconversion. These findings clearly push for more research and, perhaps our treatment guidelines for when to start therapy should be adjusted according to gender.
Baby IssuesIn the area of perinatal transmission, one study (oral abstract 120, M.G. Fowler) conducted in Africa found that transmission rates among women receiving nevirapine (Viramune) at delivery vs. women receiving AZT were significantly lower overall. They also found that nevirapine is more effective than AZT in preventing transmission in women who have advanced HIV disease.
People Over 50A study at Johns Hopkins in Baltimore looked at a group of 2,500 people at an inner city clinic. The study found that the death rate of older patients who don't use HAART is more than twice that of patients under 50. Which means it is even more important for older persons to get diagnosed and into treatment early. Being on HAART for older people definitely has an effect on survival rates.
Coping With Side EffectsThere were quite a few presentations looking at various problems related to HAART therapy. There were a number of abstracts looking at issues such as lipodystrophy and cardiovascular disease. Very few seemed to offer any real solutions to these problems. There was one study (oral abstract 32, A. Carr), which looked at whether or not switching out AZT, or d4T for abacavir in patients with facial lipoatrophy (which is the thinning of the fat pads in the face) would improve the condition. The study, conducted primarily in men (98 percent) showed that by switching to Abacavir, they could improve the lipoatrophy, but it did not go back to normal.
Before HAARTAnother study compared current HIV-positive patients with the same clinic's patients in 1993, before HAART became available. It found that neurological problems like neuropathy (the numbing of the hands and feet) are more common in today's patients than they were in 1993. This is particularly true for patients who have taken a "D" drug such as ddI or d4T, and also for older patients. This is the problem that we are faced with regarding HAART therapy. Although the medications appear to be increasing the life-span of many people, they can also impair the quality of life when taken for long periods of time. More serious, however, is the understanding of the growing risk of heart (cardiovascular) disease in HIV-positive people. Several studies examined this risk. They found that patients with undetectable viral load who were taking Crixivan tended to suffer from chronic inflammation and other heart disease risks. Other studies showed that taking any protease inhibitor increased patients' risk for developing other types of heart disease which can lead to heart attacks.
What's New?There are currently several exciting new classes of anti-HIV drugs in development. In addition to these "pipeline" drugs, there are also several "new formulations" of existing anti-HIV drugs and/or new ways to combine them together that may make them more tolerable and easy to take. One of these new formulations (poster 411) is an extended-release formula of the existing NRTI Zerit, now to be called Zerit XR. This new formulation which is not yet available could make Zerit a once-a-day pill. The preliminary results showing safety and efficacy (efficacy meaning how well it works) data concluded that persons taking Zerit XR (plus other HIV meds) and the original formulation did about the same and didn't seem to have any more side-effects with the once a day dose than they do with the standard twice daily dose.
In another study (409-W, J. Eron et al.) scientists looked at different dosing schedules of Kaletra (lopinavir/ritonavir) comparing an 800/200 mg once-a-day dose to the standard 400/100 mg twice-daily regimen. The study was conducted on people who have never taken antiretrovirals before. The study found that there is a high concentration of Kaletra maintained in the blood over a period of time (due to the small amount of ritonavir that is included in the formulation to boost its potency). This can make it possible for people to take Kaletra once daily instead of two times a day. The safety and efficacy data were similar for the two regimens through 48 weeks, and side effects did not seem to be increased in the people taking the once daily dose. Ritonavir has been shown to increase drug levels in Kaletra (and has been studied recently for use in combination with many PIs). Another study which took place in Spain (abstract 441, Lopez-Cortez et al.) looked at whether or not a "nuke-sparing" regimen could be put together using 600 mg of Sustiva (Effavirenz) plus Saquinavir 1,200 mg, and adding a dose of 100 mg ritonavir (Norvir). During the past couple of years, the focus has been on finding "PI-sparing" regimens to hopefully prevent some complications such as lipodystrophy.
Now, as people have fewer options, researchers wanted to see if they could find a workable regimen for people who may already have high resistance to the nukes (nukes meaning: AZT, 3TC, etc.). Normally, saquinavir and Sustiva would not be used together because Sustiva causes the saquinavir to be metabolized very quickly by the body, thereby decreasing levels in the blood and increasing the chance of developing resistance. It was thought that perhaps by adding a little ritonavir to the saquinavir, this might reverse the problem with the Sustiva. The study evaluated the pharmacokinetics (which is what happens to the drug once you take it), safety, and efficacy. At the end of a year, the data showed that their idea was correct, and people generally did well. Those that entered the study with a viral load of less than 50 remained undetectable, and of those persons who had a high viral load to begin with, 13 out of 20 became undetectable. (This is a possible option for people who may need it).
Another drug that is already approved for once-daily dosing and is the newest HIV medication on the market (in a new class called NtRTIs) is tenofovir (Viread). Data (abstracts 413-W through 416-W) showed that tenofovir is very effective in reducing viral load for persons with lots of prior treatment experience, and also in people who have never been on meds. Side effects are minimal for tenofovir as compared to people who only took a placebo (or fake pill) in the study.
A new medication that is not yet approved but is looking good is atazanavir (TAZ for short). This is a new once a day Protease Inhibitor currently in clinical trials by Bristol Myers Squibb. Data presented at Retrovirus (abstract 42, D. Haas) showed that when used in combination with Saquinavir in patients who have failed a prior regimen, atazanavir was well tolerated, effective in reducing VL, and did not seem to have the same cholesterol and triglyceride increases that are seen with some of the other PIs.
Currently there are several exciting compounds being developed. The first is T-20 (which many people have heard about for years but have yet to see). This medication is in a class called "entry" inhibitors and so far is in injectable form. T-20, (which attempts to prevent HIV from fusing itself into our T-cells) is still in phase III trials and so far shows good success at lowering the viral load in people with a lot of treatment experience. One abstract (418-W, J. Lalezari et al.) showed that T-20 is effective in people who have already been on a PI and have developed some resistance, but are just starting an NNRTI for the first time. Another study showed that doubling the dose of the drug would allow patients to cut the number of injections to one every 12 hours and have the same effectiveness.
Another interesting candidate is SCH-C, (abstract 1, J. Reynes) This is also in the class of drugs called "entry inhibitors," but this one is in a sub-group called co-receptor antagonists. It interacts with one of the receptors (CCR5) that HIV uses to attach itself to our T-cell and get in. In a very small and short study, data showed that the drug has been successful in reducing viral load among the 12 patients currently enrolled, and proves the CCR5 receptor to be a viable target for antiretroviral therapy.
There are also five additional drugs described as co-receptor antagonists in development. One of these is AMD-3100 (oral abstract 2, D. Schols). It works as a CXCR4 (the other co-receptor that HIV uses) antagonist. In a phase II study conducted in 40 HIV-positive patients with VL more than 5,000 copies, the drug was administered intravenously for 11 days. The antiviral efficacy and safety of AMD-3100 was evaluated and the results were good, however more research needs to be done. As more information becomes available about AMD-3100 and other new compounds, Women Alive will keep our readers updated on these developments.
Bottom LineTry to live as healthy as possible, especially if you are taking anti-HIV medication. Learn about your treatment options. Find out what may be "on the way" to becoming approved. Do some of your own research with your treatment advocate and your doctor and decide on when to start and with what medications in what combinations are best for you.
Back to the Women Alive Summer 2002 contents page.
This article was provided by Women Alive. It is a part of the publication Women Alive Newsletter.