How Has Magic Johnson Survived 20 Years with HIV?

On Nov. 7, 1991, Los Angeles Lakers point guard Earvin "Magic" Johnson shocked the world when he announced that he had contracted HIV, the virus that causes AIDS. After the press conference, the perception was that Johnson had just pronounced his own death sentence.

Yet, 20 years later, the now-52-year-old Johnson is going as strong as ever in his roles as a sports analyst, businessman and HIV activist. In 1991, when most of what people knew about HIV/AIDS was that it lead to death at a young age, this outcome might have seemed impossible.

So why is Johnson still alive?
The answer to Johnson's survival is far from "magic." According to reports, he takes the same kinds of drugs that are available to other HIV patients in the developed world, and increasingly in impoverished nations in Africa and Asia, where the disease still runs rampant. Many people have lived with HIV even longer than Johnson.

"There is nothing unique about Magic," said Spencer Lieb, senior epidemiologist and HIV/AIDS research coordinator for the Florida Consortium for HIV/AIDS Research. "There are still people alive and kicking and doing very well 20 and 30 years after infection."

Lieb said that in the state of Florida alone, hundreds of patients have hung on since becoming infected with HIV in the early 1980s, when the first confirmed AIDS cases turned up in the United States. But Johnson and these people are still in the minority: According to research and estimates by Centers for Disease Control and Prevention, about 1.2 million Americans have HIV, and 20 percent of them are undiagnosed. Approximately 50,000 people become infected each year, and more than 18,000 die annually.

Stopping HIV in the back court
The key with Johnson and others has been preventing their incurable disease from progressing into full-blown AIDS.
Upon infection with human immunodeficiency virus (HIV), a person's immune system kills off nearly all of the virus and infected cells. But some small number remain, and over time, those HIV cells replicate, and replicate, and replicate. Then, usually 10 years after the initial infection, the viral load reaches a critical count, and the virus begins killing off the vital immune cells that protect us against infections.

At that critical count, a person is considered to have acquired immunodeficiency syndrome (AIDS); with the body’s immunological defenses destroyed, it's usually only a matter of months before a range of opportunistic infections and cancers complete their lethal work.

Researchers have developed a number of powerful drugs to help people like Johnson avoid this fate. The key weapon has been a regimen of three or four antiretroviral drugs, collectively known as highly active antiretroviral therapy, or HAART.
According to a Newsweek story from last spring, one of Johnson's doctors who helped pioneer the treatment placed him on the then-experimental drug cocktail in 1994, about a year and a half before it came into widespread use in 1996.

"Magic got a jumpstart on experimental drugs before they were released to the general public," Lieb told Life's Little Mysteries, "but there were many people in clinical trials benefitting at the same time."

The meds that slam dunk HIV
HIV spreads by hijacking a subset of white blood cells called T cells, which are the body's first line of defense against foreign invaders, and using the cells' DNA to make copies of itself or replicate; in this process, these T cells get destroyed. The most common drugs in the HAART regimen target two of the enzymes that HIV uses to replicate itself.

The first enzyme, called reverse transcriptase, turns the virus' genetic instructions encoded in a single RNA strand into double-stranded DNA. (In scientific terms, this mode of replication classifies HIV as a retrovirus, hence "antiretroviral" drugs.)

The second enzyme, known as protease, creates new, functional HIV virus particles by cutting up the proteins cranked out by our hijacked cellular machinery.
Medication can disrupt these processes, and to that end, Johnson is currently taking reverse transcriptase inhibitor and protease inhibitor drugs, which are contained in the pharmaceuticals Trizivir and Kaletra, respectively, as reported by Newsweek.

Although these and other HIV-fighting drugs are "hideously expensive," Lieb noted, so are a substantial number of prescription drugs for much more everyday diseases.

Public and private medical insurance, as well as various assistance programs, make the medicines affordable and available to the vast majority of patients in the United States and other parts of the world. It is a "myth," said Lieb, that Johnson, who is wealthy, is buying himself special treatments.

Staying in the game
By taking the right regimen every day, most HIV patients can see the number of virus particles in a sample of their blood, or viral load, become undetectably low.
Not only does a low viral count stave off symptoms of HIV and AIDS, but it also slashes the odds of a randomly mutated copy of the virus emerging that can prove resistant to the therapy. Furthermore, a low viral load severely reduces the risk of transmitting the virus to others.

Yet even without modern drugs, in rare instances an HIV-positive person can manage on their own to keep AIDS at bay. These "long-term nonprogressors" or "elite controllers," estimated at as few as one in 500, have lived for decades with HIV, despite not being on antiretroviral therapy.

It is not known if Johnson is among this "scarce breed," as Lieb called them, but more than likely "without medications, he'd be progressing."

Researchers continue to study long-term nonprogressors for get insights on HIV resistance that could help the 33 million people battling the virus.
As Johnson has prominently shown, however, those with HIV can still live productive lives. Lieb has seen many such promising cases in person. "We have very buff-looking, healthy-looking HIV patients who have been infected for ages," Lieb said. "You can't tell the difference between them and you and me."

LiveScience.com

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Health/A Way to Fight the AIDS Virus With a Virus

Image credit: 3d4Medical.com/Corbis

Controlling the spread of HIV, the viral precursor to AIDS, is daunting but essential to getting the as-yet incurable epidemic under control. UC San Diego biochemist Leor Weinberger came up with a novel approach to the problem: he and his colleagues at San Diego and UCLA have engineered a particle that piggybacks on the virus as it moves between individuals and then competes with it once they're both inside a cell.

In simulations, the researchers found that, over 30 years, these therapeutic interfering particles (TIPS) could reduce the number of people in Sub-Saharan Africa infected with HIV to one-thirtieth of the current level. With about 33.3 million people infected worldwide in 2009 and 68 percent of all people living with HIV located in Sub-Saharan Africa -- according to the World Health Organization -- this new technique's potential is tremendous.

TIPS are made from harmless fragments of HIV, omitting some key pieces of genetic information like how to self-replicate. In order to survive then, TIPS need to use DNA from the actual virus to copy themselves, meaning they cannot live on their own without the virus. The particles also contain a few gene sequences engineered to inhibit HIV and, because they derive from it, both viruses use some of the same proteins and must compete for them once inside a cell. This makes replication harder for the HIV. And since TIPS can last for years in a body, they might also help keep AIDS away for an extra 5 or 10 years.

The most rampant-spreaders of HIV tend to be intravenous drug users and sex workers, who are often more difficult to reach for prevention and drug treatment, leading to their disproportionately higher rates of infection. TIPS, with its latent virus-on-virus method of attack, could be a phenomenal way to address HIV infection in this group. Beyond simulations and cell cultures though, TIPS has not yet been tested in humans, though.

Weinberger is speaking to bioethicists and working carefully with his colleagues to asses the risk of using TIPS, since no one knows how these viral particles will evolve and mix with other genetic material once they're let loose. However in the UCSD news release, he did mention that similar transmissible disease-fighting methods, like the oral polio vaccine, are already in use. As the release puts it, “Public health officials see this transmission as a benefit; it is one reason why this form of polio vaccine was chosen for the worldwide effort to eradicate the disease.”

If SLC Puck taught me anything, it was that it's hard to fight the system from without. TIPS -- and perhaps other engineered viruses in the future -- could be modern medicine's way of getting inside an epidemic at the genetic level.

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New potent and broadly effective antibodies against HIV found

A team of researchers at and associated with the International AIDS Vaccine Initiative (IAVI), The Scripps Research Institute, the biotechnology company Theraclone Sciences and Monogram Biosciences Inc., a LabCorp company, report in the current issue of Nature the isolation of 17 novel antibodies capable of neutralizing a broad spectrum of variants of HIV, the virus that causes AIDS.

The new antibodies, large protein molecules that bind to pathogens and flag them for destruction, were isolated from blood serum samples collected in a continuing global search for broadly neutralizing antibodies (bNAbs) launched by IAVI. They should provide researchers with a new set of targets for the design of vaccine candidates that can elicit similar antibodies to protect people from contracting HIV. Some of the bNAbs blocked HIV infection of cells as much as 10 to 100 times as potently as previously discovered bNAbs.

“Most antiviral vaccines depend on stimulating the antibody response to work effectively,” said Dennis Burton, a professor of immunology and microbial science and director of the IAVI Neutralizing Antibody Center at The Scripps Research Institute in La Jolla, Calif. Professor Burton, one of the senior authors of the study, is also a member of the Ragon Institute, in Cambridge, Mass. “Because of HIV’s remarkable variability, an effective HIV vaccine will probably have to elicit broadly neutralizing antibodies. This is why we expect that these new antibodies will prove to be valuable assets to the field of AIDS vaccine research.”

Only a minority of people who are HIV-positive begin to produce bNAbs after several years of infection. Animal studies suggest that such antibodies could block HIV infection if they were elicited by a preventive vaccine. Researchers prize bNAbs because their structural and biochemical analysis can reveal how to achieve a preventive vaccine. Specifically, scientists expect that they can use information about how bNAbs bind to HIV to construct immunogens—the active ingredients of vaccines—that elicit similar antibodies. The potency of bNAbs matter because a highly potent antibody could confer such protection at relatively low levels.

“Solving the neutralizing antibody problem is perhaps the greatest challenge facing the field today,” said IAVI’s chief scientific officer, Wayne Koff. “IAVI concluded many years ago that unlocking the information stored in bNAbs was going to be essential to the fulfillment of our mission—ensuring the design and development of broadly effective AIDS vaccines. This is why we support several laboratories around the world that are designing novel vaccine candidates on the basis of what we’re learning from such antibodies. We have no doubt that these new bNAbs will contribute a great deal to our own immunogen design efforts and, we hope, those of other researchers working on AIDS vaccines.”

In that regard, the new bNAbs are encouraging. Many of them bind hitherto unknown molecular structures, or epitopes, on the surface of HIV. This means that they could significantly broaden the target options researchers have in designing vaccines to elicit similar antibodies.

How the antibodies were discovered

The 17 new bNAbs described in the current Nature report were isolated from four HIV-positive individuals. The effort, sponsored by IAVI, is unprecedented in scale and distinguished by its emphasis on identifying antibodies that neutralize subtypes of HIV circulating primarily in developing countries. It had previously yielded three potent bNAbs, two of which, PG9 and PG16, were isolated by this research team in 2009 and described in the journal Science. Another bNAb was subsequently isolated from these samples by researchers at the Vaccine Research Center of the National Institutes of Health, who have also discovered a set of bNAbs from separate blood samples using an entirely different approach.

Both the previous and current studies used Theraclone Science’s highly sensitive I-STAR™ technology to isolate the antibodies. The new crop of bNAbs, like PG9 and PG16, was rescued from cell cultures derived from single antibody-producing B cells used for antibody discovery and development. Theraclone Sciences Executive Chair and Interim CEO, Steven Gillis commented, “We’re delighted that I-STAR has provided essential support in identifying bNAbs that will contribute to advancing AIDS vaccine development. In this project, and in our own infectious disease and cancer programs, the I-STAR platform continues to demonstrate a remarkably powerful ability to isolate rare antibodies with unique properties. Theraclone values these collaborative opportunities in which I-STAR can be used to help improve treatment for critical diseases.”

Monogram Biosciences, which also participated in the discovery of PG9 and PG16, conducted the neutralization assays essential to isolating the new bNAbs. The serum samples from which they were isolated represent the top 1% of all such samples gathered by IAVI and its partners, in terms of the number of HIV variants they neutralize and the potency with which they do so.

“Monogram has developed a highly skilled scientific team capable of taking on a variety of biomedical challenges,” said Chris Petropoulos, Vice President, Laboratory Corporation of America Holdings, Research and Development, Monogram Biosciences. “Their expertise and innovation has been invaluable to the discovery of these new antibodies. This research illustrates the important role different sectors of the research and health care community can play in supporting global health initiatives.”

The analysis of the new antibodies also hints at how future vaccines ought to be formulated to maximize their effectiveness. On the basis of their analyses, the authors of the report conclude that AIDS vaccine candidates that seek to effectively harness the antibody response should probably attempt to elicit certain combinations of bNAbs if they are to provide truly comprehensive protection from HIV.

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