The Body Covers: The 10th Conference on Retroviruses and Opportunistic Infections
Conference Coverage for Everybody: Retrovirus 2003
Search for a Cure Hosts Recap of 2003 Retrovirus Conference
March 5, 2003
For a full audio webcast of meeting, click here.
If reading The Body's detailed coverage of the 10th Conference on Retroviruses and Opportunistic Infections (also known as the Retrovirus conference, or CROI 2003) makes your eyes glaze over, you're not alone. Medical conferences are for doctors, after all, and the research presented at them can be awfully hard to figure out for anyone without an M.D. Still, for anybody looking to stay on top of the latest in HIV prevention or treatment, what comes out of these major HIV conferences can be extremely useful.
That's why it's so essential that organizations like Search for a Cure exist. SFAC, a nonprofit HIV advocacy group in Boston, hosted a free community luncheon right after the Retrovirus conference ended on Valentine's Day. They had a pair of HIV experts -- Dr. Cal Cohen, a prominent physician who is research director of the Community Research Initiative of New England and an instructor at Harvard Medical School, and Dr. Sigal Yawetz, an associate physician at Brigham & Women's Hospital in Boston -- give the non-M.D. world a superb rundown of the conference's highlights. Here's what they had to say.
Ask any two doctors what the verdict from this study (called the "2NN" study) was, and you're likely to get two different answers. That's because the study -- partially funded by the company that makes Viramune (NVP, nevirapine) -- provides fans of either drug with support for their arguments. Dr. Cohen's take? Both drugs work very well, but Sustiva (EFV, efavirenz) is a "tiny bit" more effective than Viramune in people who have never taken HIV drugs before. Sustiva suppressed viral load in about 5 percent more study participants than Viramune did, he said.
Just like all HIV drugs, Sustiva and Viramune cause an assortment of side effects. In the case of these two drugs, people are about as likely to experience some kind of side effect on one as the other (22 percent on Sustiva; 27 percent on Viramune). The devil is in the details: Sustiva is well-known for what are called central nervous system (or CNS) side effects, which can include extremely wild, vivid dreams and mood swings -- which might be especially worrisome if you've got a history of depression or mental illness. The notable side effects for Viramune are liver problems (even in those with completely healthy livers) and skin rash, both of which can be severe and, in very rare cases, fatal. Due to Viramune's liver risks, Dr. Cohen urges Viramune users to get frequent liver function tests, particularly during the first six to 12 weeks.
Dr. Cohen also discussed the results of a study comparing two widely used meds: Viread (TDF, tenofovir) and Zerit (d4T, lamivudine). "Both are performing excellently," Dr. Cohen says -- meaning both Viread and Zerit do an equivalent job of keeping HIV in one's body at bay for long periods of time. With Viread, though, there's a much lower risk of seeing the kinds of body fat changes (lipodystrophy), particularly facial wasting, that people sometimes experience with Zerit. Those who took Viread had only a 1 percent chance of developing lipodystrophy after four years, versus 12 percent of people taking Zerit.
The days of taking a fistful of pills several times a day are numbered, Dr. Cohen said. Most protease inhibitors today have doses of, at most, three pills taken twice a day, and more and more protease inhibitors are becoming available in once-a-day doses. "Most drugs are getting simpler and getting better," Cohen said. At the top of that list: Kaletra (lopinavir/ritonavir), a three-pill, twice-a-day drug that's the most powerful protease inhibitor on the market. "No protease inhibitor has ever beaten Kaletra in a head-to-head trial," Cohen said, although some have come close -- for example, fosamprenavir (GW433908, known as "908"). It's a new pumped-up version of Agenerase (APV, amprenavir) that may be approved for use in the U.S. within the next year or so. Recent studies have shown it works almost as well as Kaletra in people who have built up resistance to many other HIV drugs, and is also a powerful choice for people who have never taken HIV drugs. Another promising protease inhibitor, atazanavir (Zrivada), did excellently in clinical trials -- and there are no signs yet that the drug causes lipodystrophy, the same body-fat problems that other protease inhibitors are known to cause.
Right now only three classes of HIV drugs are approved for use here in the U.S.: protease inhibitors, NRTIs and NNRTIs. HIV treatment consists of a combination of drugs from two of these classes, under the theory that barraging HIV with different drug types will help keep the virus off its guard and under control.
Some researchers have proposed a new option for therapy, though: treatment that consists of only one class of drug -- like three or even four NRTIs, or a pair of protease inhibitors. There are two possible benefits to this strategy. First, it may be less toxic (fewer side effects): "It may be that there's something about combining these classes [protease inhibitors and NRTIs] that makes the toxicity even more likely ... and that separating these classes may allow a decrease in toxicity," Dr. Cohen surmised. Second, the one-class strategy could provide more drug options in the future by ensuring that, even if a combination fails, a person will become resistant to only one class of drugs at most.
Most hopes about the benefits of structured treatment interruptions (STIs) seem to have been shot down. A slew of new studies have found that it has little benefit, if any, for treatment-experienced HIVers hoping to take a break from meds.
Dr. Cohen reported that, according to research by Dr. Bruce Walker of the Harvard Medical Center, only about 20 percent of those who go on structured treatment interruptions have any success with them. But Dr. Cohen made it a point to note that there's an awful lot of research that still needs to be conducted in this area before any doctor can recommend it to his or her patient.
Two other types of treatment interruption show signs of promise, Dr. Cohen noted. The first is called "cycling," in which a person spends a few days taking meds, then a few days off. (Dr. Cohen himself is currently studying a strategy in which people take their meds during the work week and then stop on weekends.) The second strategy is called "CD4-based" treatment interruption, because it involves stopping and starting therapy based on a person's CD4 levels -- for instance, a person might stay off therapy as long as their CD4 count is above 350, and start treatment again whenever it drops below that mark.
Treatment interruption studies are still ongoing -- including the new SMART trial, the largest study ever to examine them -- to figure out just how much chance these strategies, and others, have of succeeding. In the meantime, Dr. Cohen warns, don't take a break from your drugs without consulting your doctor. "We know that when people stop, sometimes when the virus comes back, it can [become resistant] to the meds you just stopped -- if you don't do it right," he said. "If you're going to stop, please talk to an expert."
There are a lot of new HIV drugs in development. More this year than ever before, as a matter of fact -- and we're not just talking about new versions of existing drug types (protease inhibitors, NRTIs or NNRTIs). Entry inhibitors, for instance -- which attempt to keep HIV from invading CD4 cells in the first place -- make up a whole new class of meds. The flagship drug in this new class is expected to be approved this spring: It's called T-20 (brand name Fuzeon; generic name enfuvirtide), and ongoing studies have shown it to be very effective in those who are already resistant to most of the drugs currently on the market. The downside to T-20: It has to be injected, and sometimes a person's skin can become badly irritated where the needle was inserted.
There's more where T-20 came from, though. For people who become resistant to T-20, there's already another option being studied: T-1249, a very similar drug that appears to work even better than T-20, and with fewer skin reactions. And a whole slew of additional entry inhibitors -- as well as drugs that attack HIV using other means -- are in the works. "Some of them seem safe, some of them are working, and some of them will probably get here someday," Dr. Cohen said hopefully.
You've probably heard the rumors that your heart and HAART -- especially protease inhibitors -- may not always get along so well. Dr. Cohen talked about results from the D:A:D study, the largest ever to examine the question of whether HAART can cause heart damage. The verdict? "There's a hint of an answer that, yes, it might matter," Dr. Cohen said.
There is a "small but real risk" of heart attacks with some medications, he added, but it's important to put that risk into perspective. Smoking, high blood pressure, diabetes and lack of exercise, he said, are actually more dangerous than HIV meds in terms of increasing heart disease risk, so be sure to talk to your doctor about these risk factors before starting -- or switching off of -- any protease inhibitors. "If you're smoking and your blood pressure's high, that's where the action is," Dr. Cohen said. "So for those of you who are still smoking: reconsider!"
There have been some signs that HIV, and/or the drugs that fight it, may cause bone problems -- namely osteopenia/osteoporosis, or brittle bones, and osteonecrosis, or bone death (which can cause severe joint pain, usually in the hip). Researchers still have a lot of work to do in this area, Dr. Cohen says, but regardless of the cause, he suggests there's something that can easily counter or prevent it: Take vitamin D and calcium. A small but important study in St. Louis found that by taking 70 mg of alendronate (a supplement, also available under the brand name Fosamax), 1,000 mg of calcium and 400 units of vitamin D every day (which you can get during the summer just by standing outside in the sun for a few minutes), people may be able to effectively treat bone disorders associated with HIV infection.
You may already have heard about this potential treatment for facial wasting: New-Fill, a gooey, silicone-based substance that can be injected underneath the skin. Studies suggest it's pretty effective, Dr. Cohen says: "It looks real, and it looks like it works." As with any good news, though, there's always a catch. For New-Fill and other drugs like it, the catch is that they have not yet been approved by the Food and Drug Administration for treatment of facial wasting in the U.S. Keep your ears and eyes open, though: Some doctors in the U.S. are using New-Fill anyway, so ask around if you're interested in giving it a shot. (If you're in France or Mexico, New-Fill has been approved for use there; so it'll be much easier to find.)
Our 42nd President gave the keynote speech at the beginning of the conference, and he had a lot to say -- particularly about the dire HIV situation in sub-Saharan Africa, and how important it is that we -- not only our government, but you and I as well -- do something about it before it's too late.
Clinton didn't ignore the worsening HIV epidemic here at home, though. In fact, he talked at some length about what he felt was one of the biggest mistakes he made as president: fighting efforts to institute nationwide needle exchange programs. Needle exchange -- which involves setting up safe havens where injection drug users can go to trade used needles for clean ones -- has repeatedly been proven effective in reducing the spread of HIV, but due to a complete lack of support at the top of the political ladder, such programs exist in very few places within the U.S. and Canada.
"This country's a disaster when it comes to addressing the issues of injection drug use," Dr. Cohen said. "We should be proactive and say, 'You know what? If you've got a needle addiction issue, we'll try to get you off it -- but while we're working on that, we'll give you a clean needle.'"
The U.S. Centers for Disease Control estimates that as many as a third of all people with HIV in the U.S. have no idea they're infected -- a dangerous fact, not only for the HIV-positive person who might need treatment, but also for his or her sexual partners, who may not know they're at risk. To cut down on that number, the CDC recommends that hospitals in high-prevalence areas (where more than 1 percent of the population has HIV) routinely offer HIV testing and counseling.
Very few hospitals do this, however -- even though, as Dr. Yawetz asserts, the practice works. She mentioned a study presented at the Retrovirus conference, in which the emergency rooms of the four Massachusetts hospitals with the highest number of reported HIV infections started a program called "Think HIV," which provides everyone who wants it with HIV testing, counseling and referral to treatment care. The number of new HIV infections that the hospitals were able to catch -- especially infections among people who said they didn't think they were at high risk -- was far higher than at hospitals and clinics throughout the rest of the state, where Think HIV programs were not in place.
The moral of this story is kind of a no-brainer: If you offer people care, they'll come get it. More hospitals should start Think HIV programs, Dr. Yawetz said -- if more of them did, they could greatly increase the number of people aware of their HIV infection. It's also extremely important for HIV educators to encourage people to get HIV testing, she said, and to help eliminate the stigma associated with HIV so that people will be more willing to find out whether or not they have it. That way, they can help prevent other people from getting HIV as well.
"I'd like to encourage all of you and all of your friends to enroll in studies," Dr. Yawetz pleaded to the women assembled, "so we can say more meaningful things to women with HIV infection when we come to make treatment choices." Because so few women participate in clinical trials, researchers and physicians know little about the unique medical problems HIV-positive women might encounter -- or how to fix them.
Take side effects, for instance: There's "very little informative data" on the unique ways in which lipodystrophy affects women, Dr. Yawetz said, although there are definite signs that women do experience a different type of fat gain/loss than men. In addition, there are conflicting signs regarding whether or not HIV infection harms women's bones: One small study at the conference said it did, and one said it didn't. The bottom line, though: Dr. Yawetz says that female HIVers and their doctors should regularly discuss, and check for, signs of lipodystrophy and bone problems -- and join studies that can help researchers learn more about these and other issues.
Dr. Yawetz discussed a fascinating study in Uganda, which found that HIV is most likely to be transmitted during two key time periods: 1) during the first five months after a person has been infected, and 2) five to 15 months before a person dies from his or her HIV infection. The reason: Those are the two times when viral load tends to be the highest. "The fact that early after infection and then late -- before death -- there is higher transmission suggests that ... people with higher viral load are transmitting HIV much more efficiently," Dr. Yawetz said.
Although the study was conducted in Uganda with serodiscordant couples (one positive, one negative), Dr. Yawetz says the results are useful for people throughout the world. These results can help HIV prevention and treatment experts better coordinate their efforts to keep people from passing HIV to someone else, and also point to the importance of getting tested, and treated, as quickly after HIV infection as possible -- something OraQuick, the new 20-minute HIV test, should make much easier.
After Drs. Cohen and Yawetz brought us through the highlights of the conference, they were joined by John James (editor of AIDS Treatment News) and Jules Levin (the executive director of the National AIDS Treatment Advocacy Project) for a Q + A session with the hundred or so HIVers and HIV educators who gathered for the meeting. A full transcript and audio files from that extremely informative session -- a must-read (or hear) for anybody with basic questions about HIV, prevention and treatment -- will be available soon on our site. We'll link to it from this article as soon as it's up!
For loads more details about these studies and many others presented at this year's Retrovirus conference, be sure to read The Body's coverage!
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