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This Month in HIV: Summary of "Top 10 HIV Stories of the Past Year"

May 2008

A Cavalcade of New HIV Meds

The Story: HIV is one of the most rapidly evolving fields in medicine, but even so, the clip at which new HIV medications have been approved lately is stunning. And we're not just talking about new meds in existing drug classes; we're also talking about meds that work in ways no other HIV medication has worked before.

In the second half of 2007, the U.S. Food and Drug Administration approved three antiretrovirals: Isentress (raltegravir, MK-0518), the first integrase inhibitor; Selzentry (maraviroc, Celsentri), the first CCR5 inhibitor; and Intelence (etravirine, TMC125), the first non-nucleoside reverse transcriptase inhibitor (NNRTI) that may work even if a person has resistance to other NNRTIs, such as Sustiva (efavirenz, Stocrin) and Viramune (nevirapine).

A fourth new drug, the protease inhibitor Prezista (darunavir, TMC114), was approved back in 2006. In the past year, however, new research has suggested that Prezista may work quite well not only in people with a lot of HIV drug resistance, but in people who are just starting HIV treatment as well.

What It Means: After many years in which people with a lot of HIV drug resistance had few options and little hope that a new medication would come along, we suddenly have a fistful of them. This is critical because an HIV treatment regimen works best when it includes at least two meds that are able to work at full power. The more new meds we have, the more likely it is that a person can find a regimen with at least two active drugs.

Until 2007, Dr. Wohl explains, "There weren't enough new medicines to craft a regimen that was likely to work in people whose HIV was already resistant to a lot of HIV medications. With these newer drugs, there's now more to pick from. ? It opens up tremendous new opportunities for people who, before these drugs came about, didn't have any opportunities."

Another plus: We may begin to see some of these drugs making their way into first-line therapy within the next few years, opening up new possibilities for people who are just starting HIV treatment.

To download an MP3 of this part of the interview, click here.

Too Many HIV-Positive People Get Diagnosed Late

The Story: In the United States, we're in the midst of a revolution in HIV care brought about by an abundance of powerful new HIV medications. That's the good news. The bad news is that many people who should be on HIV treatment aren't -- often because they aren't aware that they were at risk and so don't get tested for HIV; by the time many individuals are diagnosed with HIV, their CD4 count is low and their health is in danger.

An important study out of Baltimore found that HIV-positive people making their first visit to an HIV doctor or clinic have an average CD4 count of 276 -- that's lower than the average CD4 count was more than a decade ago, and it's well below the point at which most treatment guidelines recommend starting HIV meds. Men, African Americans and older people appeared to be especially at risk for having a low CD4 count at their first visit to an HIV health care professional.

What It Means: "This is really concerning, because it means people are showing up late," says Dr. Wohl. "It means people are not getting tested earlier in the course of their HIV infection. We know that people who start therapy at lower CD4 cell counts have a greater risk of side effects, and may not respond as well as people who have higher CD4 cell counts."

So what's the solution? "The glaring neon light shining here is that we should be doing more testing," says Dr. Wohl. "I think we should have routine HIV testing. You visit your doctor for your annual physical and the doctor offers you an HIV test." That way, more people find out about their HIV status earlier, get themselves into HIV care more quickly, and never have to deal with the health risks of going too long without seeing an HIV doctor.

To download an MP3 of this part of the interview, click here.

Heart Attack and HIV Meds: Not a Black-and-White Issue

The Story: For years now, a massive, ongoing, international study known as D:A:D has examined the potential link between HIV medications and heart problems. In 2007, study results were published that showed a gradual increase in heart attack risk over time in people taking HIV meds. Among specific drug classes, protease inhibitors appeared to increase heart attack risk, while NNRTIs did not.

However, it's important to note that the overall risk of heart attack remained low in HIV-positive people on treatment: Just 345 out of 23,437 people in the study had a heart attack. Further, the heart attack risk associated with HIV meds generally paled in comparison to the risk associated with smoking, high blood pressure or -- here's the kicker -- untreated HIV infection. On the whole, the more risk factors a person already has for heart disease, the more likely it is that HIV meds could worsen the situation.

What It Means: "Protease inhibitors probably increase the risk somewhat of a heart attack, but it's better than being off HIV medicines," Dr. Wohl says. "I think the most important thing is to understand that the magnitude of the change of risk in heart attacks with protease inhibitors was a fraction, really, of what you get with smoking or with uncontrolled high blood pressure -- those are the things that we can change."

It's what your mom has been telling you for years, and it's Dr. Wohl's advice as well: Don't smoke, get that blood pressure down, exercise more and eat right. The lower your heart disease risk is to begin with, the less of an impact your HIV meds will have on that risk. Avoiding HIV meds because of heart concerns may do more harm than good, since recent research has dramatically demonstrated that HIV itself, if left untreated, may be even more dangerous for your heart than HIV treatment.

To download an MP3 of this part of the interview, click here.

Defying Expectations: Kaletra, Sustiva and Body Fat

The Story: The U.S. federally funded study known as ACTG 5142 is the first clinical trial to compare two HIV medication powerhouses head-to-head: Kaletra (lopinavir/ritonavir) and Sustiva. The study found that the two drugs were pretty similar when it came to their ability to fight HIV. However, a substudy released in 2007 found some unexpected answers to the question: What impact does each drug have on metabolic issues, such as body shape, cholesterol and blood fats?

Experts assumed that Kaletra would cause more metabolic problems, since protease inhibitors were thought to be associated with metabolic side effects. They were wrong. The two drugs had pretty much the same effect on belly fat (which increased), good cholesterol (which went up) and bad cholesterol (also up).

Assumptions were also overturned when it was discovered that people who were taking Sustiva had more fat wasting in their arms and legs compared to people taking Kaletra. However, the combination of meds that make up one of the most popular first-line regimens -- Atripla (efavirenz/tenofovir/FTC) -- did not commonly cause fat wasting, even though Sustiva is a part of it.

What It Means: For years, most researchers assumed that protease inhibitors were the main culprit behind metabolic problems such as body shape changes and cholesterol issues. ACTG 5142 "opened up our eyes that we have to think anew about body shape changes, that it's not a protease inhibitor thing," Dr. Wohl says. "In fact, if anything, the protease inhibitor was associated with protection against fat wasting of the arms and legs." Not that NNRTIs like Sustiva are bad, of course; the study found that more popular NNRTI-containing combinations, like Atripla, appeared pretty safe in terms of impact on body shape. (Other combinations, however -- like Sustiva + Combivir [AZT/3TC] or Sustiva + Zerit [stavudine, d4T] -- may not be such a great idea.)

The bottom line for everyone: Don't make assumptions about HIV meds -- for better or for worse -- without the results of reliable studies to certify those assumptions.

To download an MP3 of this part of the interview, click here.

Sperm Washing Effective for HIV-Positive Men Who Want Children

The Story: Although the term "sperm washing" might conjure images of tiny faucets and microscopic washboards, the reality is a little more ? scientific. It's a technique for separating sperm (which can't be infected with HIV) from the possibly HIV-infected cells in an HIV-positive man's semen. His female partner can then be artificially inseminated with the "washed" sperm. The goal, of course, is to increase the odds that an HIV-positive man can conceive a child with an HIV-negative woman without putting her or their baby at risk for HIV.

And it works extremely well, according to a European study of more than 1,000 couples who underwent the procedure. Half of the couples successfully conceived, resulting in 410 deliveries -- and not a single woman (or baby, of course) became HIV positive.

What It Means: The study did not conclusively find that sperm washing is 100 percent safe, Dr. Wohl warns, but it did show that the "HIV risk is extremely low for an HIV-negative woman when this procedure is used." However, there are a couple of caveats to note: For one thing, sperm washing is quite an expensive process. For another, because in this study many of the women used fertility drugs, the odds were increased that a woman would become pregnant with multiple babies. "You may get more than you bargained for," Dr. Wohl says.

Still, the prospect of a baby boom among HIV-positive people, who are doing well on HIV treatment, is an exciting one. It represents a massive shift in the way that HIV-positive people -- and, we can hope, society at large -- feel about HIV-positive people having children. "What most of us can understand, now that HIV-positive people are living for so long, is how one of the things that separates HIV-positive people from people who are uninfected is the ability to have a child," Dr. Wohl says. "Now we're finding that that probably doesn't have to be the case any longer."

To download an MP3 of this part of the interview, click here.

Genetic Screening for Hypersensitivity to Ziagen

The Story: One of the big red flags with Ziagen (abacavir) -- a component of the HIV meds Epzicom (abacavir/3TC, Kivexa) and Trizivir (AZT/3TC/abacavir) -- has always been that it can potentially cause a life-threatening allergic reaction. Known as "abacavir hypersensitivity reaction," it's a side effect that impacts as many as one out of 10 people within a few days after they begin taking Ziagen. Now scientists have devised a test that may all but eliminate that 1-in-10 risk.

The idea is deceptively simple: Scientists have discovered that having a specific gene within your DNA increases your risk for developing an abacavir hypersensitivity reaction. If you don't have the gene (called HLA-B*5701, or sometimes just 5701), you're very unlikely to have the reaction. If you do have the gene, it's probably best to avoid Ziagen, or to take it with extreme caution.

So scientists developed a test to screen for HLA-B*5701. A couple of noteworthy studies published in 2007 gave the test a whirl, and the verdict was: It works really well. "There's been almost no case of anyone developing a hypersensitivity reaction who does not have this offending gene," Dr. Wohl notes.

What It Means: In the United States, the HLA-B*5701 genetic test has quickly become part of the regular battery of tests that any HIVer gets before starting treatment. Side effects are always a risk with HIV meds, but with this hypersensitivity test, at least one particularly dangerous side effect can be averted.

But there's more to this story than the warm fuzzies that come with avoiding a life-threatening side effect. The widespread use of this test marks a major landmark development not just in HIV treatment, but in all forms of medical care, Dr. Wohl says. "For years, we've been talking about this wonderful science of using a patient's genes to tailor their medical therapy, but it's all been talk. ? This is one of those examples where HIV is a leader in the medical field."

To download an MP3 of this part of the interview, click here.

Back to the Drawing Board for HIV Vaccines

The Story: Ever since scientists figured out what HIV was, they've been trying to figure out how to prevent people from getting it. An HIV vaccine has long been seen as a "holy grail" of sorts -- a tantalizing vision of a foolproof drug that can ensure that all HIV-negative people stay HIV negative, no matter what. Sadly, the results of one major study all but guarantee that an HIV vaccine will remain nothing more than a vision for the foreseeable future.

The study's name is STEP. It was a massive, international trial of more than 3,000 HIV-negative people, and its purpose was to test an experimental HIV vaccine that had showed promise in lab tests. The vaccine contained a re-engineered form of adenovirus, which causes the common cold. The theory was that the rejiggered adenovirus would reprogram a person's immune cells to make them more effective at fighting off HIV infection.

In the real world, however, the plan didn't work out: The vaccine had absolutely no protective effect against HIV, the researchers found. In fact, it turned out that people who were immune to adenovirus appeared to have a reduced ability to fight off HIV infection.

What It Means: For years now we've been seeing a nonstop string of negative results from various HIV vaccine trials, but this one really hurt. It was arguably the most promising of all HIV vaccines developed to date, and it failed utterly. "This, at the very least, puts a big chill on HIV vaccines in general," Dr. Wohl says. "Many vaccine trials were either underway and had to be stopped, or were about to start and had to be stopped."

The STEP study did not kill the idea of developing an effective HIV vaccine. But it drove home just how hard it is to create one that works, and it may send vaccine researchers back to the drawing board for years to come.

To download an MP3 of this part of the interview, click here.

Crystal Meth and HIV

The Story: There's nothing new about crystal methamphetamine, better known as meth. It's a party drug that's been around for years, and HIV prevention advocates have long been sounding the alarm about its possible connection to HIV risk behavior (especially among gay men), since the drug tends to impair judgment, lower inhibitions and make a person crave sex more than a male rabbit in springtime.

But there's much more to the meth story than the growing concern that meth use contributes to HIV transmission. Research published in 2007 showed that, for one thing, meth use is becoming much more common among homeless and marginally housed people, who are already at a higher HIV risk to begin with. Much in the same way that, back in the late 1980s and 1990s, rising HIV rates among the homeless were a red flag that HIV was spreading into the general population, these findings suggest that meth use is not confined to stereotypical groups such as gay men.

Another study released in 2007 found that meth may lead HIV-positive people to develop HIV drug resistance (perhaps by making them more likely to miss HIV medication doses). And one other important study regarding meth testified to how hard it is to kick a meth addiction once it's got a hold of you. Findings like these raise the alarming specter of a potentially deadly cycle of meth use, HIV transmission, drug resistance and poor HIV treatment outcomes.

What It Means: Meth is "incredibly devious and evil, and it's the kind of thing we don't need right now," Dr. Wohl says. "I think it's erasing ... some of the advances we had in trying to control [HIV] and the spread of this infection."

It's the future, and not just the present, that worries Dr. Wohl when he thinks about the intersection between meth and HIV. "Maybe I'm being Chicken Little and saying the sky is falling, but from all the data I'm seeing, I think that methamphetamine use is one of the biggest threats we're going to face in this country when it comes to containing HIV infection."

To download an MP3 of this part of the interview, click here.

Survival With HIV: Great Expectations

The Story: When you're diagnosed with HIV, one of the first questions that probably pops into your mind is : How long can I expect to live? It wasn't so long ago that you could count the number of years on your fingers. But now you can throw in your toes -- and a friend's toes, while you're at it -- and still not have enough. Researchers in Denmark crunched the numbers and found that a newly diagnosed 25-year-old, who takes HIV treatment, can expect to live another 32.5 years, on average. And that survival time is just a rough estimate, since new HIV meds, which were not available when this study was done, are expected to expand it even more. Survival in the HIV infected continues to be on the upswing.

What It Means: Keep in mind that 32.5 years is not a deadline; it's just an estimate. "You can't necessarily apply everything you read from one study to yourself, but this gives us sort of a ballpark figure we can use when thinking about this," Dr. Wohl says. "We certainly know that it's obsolete to say you have 10 more years to live after you get HIV diagnosed, data we had generated from 15 to 20 years ago in a different world."

There was one blip on this encouraging radar, however: People who were coinfected with HIV and hepatitis C tended to not live as long as people who had HIV alone. The findings speak to the importance of educating people about how to prevent themselves from getting hep C -- studies increasingly show that it can be transmitted sexually, especially among gay men who engage in sexual activities that may involve blood, such as fisting. They also highlight how crucial it is that everyone with HIV get tested and, if necessary, treated for hep C before it becomes a real health concern.

Still, on the whole, the Denmark study is an encouraging one for anybody living with HIV in a place where there's access to modern treatment and care. "I find this reassuring," Dr. Wohl says. "I tell people, 'Chances are that if you do most of what we talk about and take care of yourself, you can get old.' I think that this study shows that."

To download an MP3 of this part of the interview, click here.

Immune Function and the Risk of Cancer

The Story: In developed countries, HIVers are living longer, and better, than they ever have before. And thanks to ever-more-effective HIV medications, the diseases that were once the hallmarks of the HIV pandemic -- such as pneumonia, thrush and toxoplasmosis -- are no longer the most common illnesses that strike HIV-positive people in wealthier nations. So when people with HIV living in the developed world die nowadays, what is it they're dying from?

We are learning that "cancer" is more and more often the answer to that question. We're not just talking about Kaposi's sarcoma or non-Hodgkin's lymphoma, the cancers that were traditionally associated with advanced HIV disease back in the 1980s and 1990s. An important study published in 2007 found that HIV-positive people are more likely than HIV-negative people to develop a range of different cancers, particularly those that are often caused by viruses, such as anal/cervical cancer (which can be caused by human papillomavirus) and liver cancer (which can be caused by hepatitis B or C). In fact, the study found that HIVers develop cancer at roughly similar rates to people who have had organ transplants (another group of folks who tend to have weakened immune systems).

What does your immune system have to do with fighting cancer? Everything, it turns out. "Most of us think of the immune system as protecting us against germs. The immune system also protects us against cancers," Dr. Wohl explains. "We're just starting to understand that over the last several years. ... In people who have problems in their immune system, that protective mechanism is faulty. That's why we do see cancers in people with HIV infection."

What It Means: Dr. Wohl puts it simply: treatment, treatment, treatment. The study on cancer and HIV "really indicates to us that we cannot tolerate poor immune function among people with HIV infection," he says. "Do we allow people's [CD4] counts to go down so low that we may be placing them at risk for these infections that could lead to cancers?"

Just how low is "too low" when it comes to CD4 count is still an open question, and one that researchers will have to flesh out over the months and years to come. But for Dr. Wohl, this study supports recently updated recommendations to HIV treatment guidelines in the United States and Europe, which now urge people to begin taking HIV medications before their CD4 count drops below 350.

To download an MP3 of this part of the interview, click here.

Runners Up

HIV Among Street Youth in St. Petersburg

HIV is cutting a huge swath through street youths in Russia's second-largest city. A new study found that a stunning 37 percent of street youths between 15 and 19 were found to have HIV, with rates nearing a mind-numbing 70 percent among those with neither a mother nor father and kids with no place to live. "These are numbers that blow away seroprevalence studies of HIV in Africa," Dr. Wohl marvels. "This is just total neglect of a group of people within a society."

The chilling statistics may be a harbinger of what's to come if more isn't done to reach out to marginalized youth in Eastern Europe. Dr. Wohl predicts that in 25 years, "Eastern Europe is going to be where people think about HIV. Right now we think about Africa, but the rate of HIV infection is climbing so steeply in parts of the former Soviet Union that in a decade or two when we think about HIV, it's going to be in that part of the world."

Does HIV Accelerate Aging?

As more HIVers in developed countries live into their 50s and beyond (or are diagnosed when they're in their 50s or beyond), we've begun to see a growing focus on HIV and aging. This focus has revealed some unsettling findings. For instance, research published in 2007 suggests that people who are getting older with HIV may also be getting older because of HIV. "There is a picture emerging that HIV does seem to cause more advanced aging in many people," Dr. Wohl says.

For many years, HIV research focused on preventing people from dying rather than helping them grow old gracefully. As a result, aging and HIV remains an area about which we know extremely little. Although it seems clear that HIV treatment helps reduce the aging effect of HIV, the underlying cause of that effect remains a mystery. "We're just at the beginning of understanding what's going on biologically," Dr. Wohl explains.

In the meantime, Dr. Wohl's advice is simple: "We do know that the immune system ages prematurely in people with HIV, so we should do everything we can to keep that immune system healthy and happy." That means not just taking HIV meds, but eating right, exercising, reducing stress and -- above all -- not smoking cigarettes. "You don't have to be a scientist to see the deleterious effects of smoking on the body and how it can facilitate the problems that we think about as we get older."

Underestimating HIV Rates in the United States

For many years now, the official estimate of new HIV infections from the U.S. Centers for Disease Control and Prevention (CDC) has held steady at around 40,000 per year. Frontline HIV prevention workers have long been skeptical of that number, however -- and in late 2007, we got our first inkling that U.S. health officials may indeed increase those estimates. A Wall Street Journal article, citing a CDC source, said that the agency was debating an increase in its HIV estimates by 10,000 to 15,000 people per year. (A newly released surveillance report from the CDC further supports the likelihood of an increase in annual HIV estimates.)

So far, there's been no official word that estimates are about to go up, but even the current numbers are disturbing enough. The United States is a country that's extremely powerful, ridiculously wealthy, and supposedly one of the leaders in the global fight against HIV. And yet, for years now, it has failed to reduce the tide of HIV within its own borders. "I find this a very concerning development, despite all the millions of dollars and all the intelligence and the conferences that have been dedicated to HIV prevention," says Dr. Wohl. "It's a shame that we're not seeing the decrease that we thought we should be seeing with all this effort." It may be time to step back and refocus our HIV-fighting efforts on the essentials, Dr. Wohl suggests. "[This story] really tells us that we have to go back to the drawing board and figure out what works, and how to get that to work in different populations."

To download an MP3 of this part of the interview, click here.


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