When we think of the AIDS epidemic, many of us turn to the developing world, overlooking the fact that HIV is very much a problem here in the United States. Every year some 50,000 people in this country are newly diagnosed with HIV, and many of these individuals previously had no idea they were infected with the virus.

To help prevent further spread of the disease, which affects an estimated 1.2 million Americans, the U.S. Preventive Services Task Force has issued (.pdf) a final recommendation that every adult between 15 and 65 be screened for the virus. Younger adolescents and older adults considered at risk also should be screened, as well as all pregnant women in labor whose HIV status is not known, the task force suggests.

“Treatment for HIV has advanced remarkably, helping people live longer and healthier lives, and reducing HIV transmission,” Stanford professor Douglas K. Owens, MD, one of the members of the task force, told me last week. “Treatment is most effective when offered early in the course of HIV disease, typically well before people have symptoms, and screening enables people to learn they have HIV in time to get the full benefit from treatment.”

“Screening is especially important because up to quarter of people who have HIV do not know they have it,” Owens added.

Studies have shown that people who are infected with the virus are significantly less likely to pass it along if they are receiving ARV treatment, which reduces the amount of virus circulating in the blood. Moreover, people who are infected are more likely to do better - suffering fewer opportunistic infections - if they receive treatment early on, rather than wait until symptoms occur and the disease becomes more advanced. For these reasons, identifying infected individuals through universal screening makes good public health sense.

The task force’s latest recommendation, published in the new issue of the Annals of Internal Medicine, is in keeping with the guidelines of the American College of Physicians, the American Academy of Pediatrics and the federal Centers for Disease Control and Prevention. Owens talked more about this issue with me last fall, after the task force’s draft recommendations were released.

Previously: Stanford expert discusses recommendation for universal HIV screening, Task force issues draft recommendation for universal HIV screening and National HIV screening and testing could be very cost-effective

As a reporter for a Palo Alto newspaper in the early 1980s, I interviewed Ed Engleman, MD, director of the Stanford Blood Center, about the blood center’s introduction of a novel HIV screening test, the first of its kind in the country.

Thirty years later, I revisited the test - and all the controversy surrounding it – as it would prove to be a landmark period in blood-banking history. What I discovered is detailed in a new story in the latest issue of Stanford Medicine magazine.

Fortunately I was able to plumb the memories of Engleman, who is still directing the blood center, as well as Herbert Perkins, MD, now 94, who directed the Irwin Memorial Blood Bank in San Francisco at the time. Because San Francisco was then an epicenter of the epidemic in the United States, Perkins was in the eye of the storm, trying to protect the blood supply while respecting the civil rights and privacy concerns of those in the gay community, where HIV was prevalent.

The debate about how to ensure the safety of blood supplies took place at a time when very little was known about HIV/AIDS. It was a true scientific mystery, with researchers speculating about the cause of this strange and deadly illness, which then had no name, and postulating about the potential for its spread through blood transfusion.

Another interesting perspective for the story came from Jeff Lifson, MD, now a leading AIDS researcher at the National Institutes of Health, who was a resident at Stanford working in Engleman’s lab during the crisis. He and Engleman both remembered the feeling of being ostracized by blood banking colleagues for introducing what they believed was - and what would later prove to be – a life-saving test.

Previously: New issue of Stanford Medicine magazine asks, What do we know about blood?

In the last few days, there has been much talk about the baby born with HIV who was reportedly cured of the disease – only the second documented case of an AIDS “cure.” Like a good scientist, Yvonne Maldonado, MD, a pediatric AIDS expert at Stanford, is a bit skeptical and says there are many questions yet to be answered.

“It brings a lot of promise and hope but there are lots of details to be looked at before the next step can move forward,” said Maldonado, chief of pediatric infectious disease at Stanford and Lucile Packard Children’s Hospital. She has been doing research on mother-to-child HIV transmission for many years, working with a group of women in Zimbabwe.

According to news reports, the Mississippi mother came to the hospital in labor, and tests showed she was HIV-positive. Because the mother had never been treated for HIV, doctors knew the chance was high that she would transmit the virus to her baby. So within 30 hours of the baby’s birth, they took the unusual step of treating the infant aggressively, with a full cocktail of antiretroviral drugs. The child continued treatment for 18 months, then stopped. And when the mother brought the two-year-old back for a checkup, tests showed – remarkably – that the baby was virus-free.

One pressing question, Maldonado says, is whether the baby was truly infected. Babies can acquire HIV from their mothers in several ways – either in utero, during labor and delivery or as a result of breastfeeding.

Did this child become infected in utero with the virus, which was ultimately eliminated by the antiretrovirals? Or did the child simply carry some circulating virus from the mother in its blood – and the drugs stopped the virus from establishing itself in the baby?

“Those are two different things,” Maldonado told me. In the first case, “That would be a functional cure. The other would be preventing early post-partum infection,” a form of prevention, rather than cure.

She said there have been anecdotal reports of babies who have been able to clear the virus from their bodies. “You can find virus in infants that then disappears because they haven’t become infected,” she said.

If, on the other hand, this is truly a functional cure, then that has many implications for treatment of infants down the road. “If in fact that was the case, maybe that means instead of giving light therapy to prevent infection, all these babies (of HIV-positive mothers) should be getting heavy-duty therapy right from the start.”

Maldonado notes that pediatrics has routinely led the way in HIV prevention and treatment, as unlike adults, one can often identify when a baby became infected – and then quickly move to intervene. She said it’s unfortunate the latest case, reported at a scientific meeting, occurred during the weekend of the budget sequester.

“Our capacity to study this will be limited,” she said. “NIH will be flat-funded, and yet here’s an opportunity to look at these paradigm-shifting concepts. But these things need resources. It may be a serendipitous finding, but it will be just that if you don’t do more science-based inquiries.”

Previously: International AIDS Conference Day Three: Daring to talk about a cure and Experts discuss German patient who appears cured of HIV

People with HIV have to take a cocktail of drugs daily to keep the lethal virus in check. But a novel gene therapy approach, now under development at Stanford, could make patients resistant to the virus and free them from this lifelong dependence on drugs, which have adverse side-effects.

In a new study, the researchers describe their technique of using “genome editing” to make T cells, key cells of the immune system, resistant to the virus. In studies done in the lab, the technique effectively blocked the virus from entering the cells through one of two receptors, known as CCR5 and CXCR4. These are the two common entry points for the virus.

In one instance, the researchers used genetic manipulation to deactivate the CCR5 receptor gene. And for added protection, they were able to introduce three known anti-HIV genes into the receptor genes. This blocked both CCR5 and CXCR4. These modified T cells had more than 1,200-fold protection, and in some instances more than 1,700-fold protection, against HIV; unmodified cells succumbed to infection in a matter of weeks, the researchers reported.

The research is still in the early stages and has to go through animal testing, as well as clinical trials. But it is a very encouraging step forward in the field of gene therapy for HIV, Matt Porteus, MD, the lead investigator told me.

“I feel this is a significant improvement in the first generation application. So I’m very excited,” he said.

Interestingly, as I left Porteus’ lab, located in the Lorry I. Lokey Stem Cell Research Building, I ran into another HIV researcher and mentioned the work, which was entirely new to him. That’s how innovative this technique is.

Porteus, a pediatrician, is interested is using the approach to treat other diseases as well. A hematologist and cancer biologist, he treats children at Lucile Packard Children’s Hospital and is hoping some of his patients, such as those with sickle cell anemia, might someday benefit from a gene therapy approach along these lines.

Eight months ago, I went gluten-free. People often ask me why and how I manage, especially with all the treats that present themselves during the holidays.

First, I do not have celiac disease. I chose to avoid gluten on the advice of a nutritionist who I consulted because of thyroid issues. I have Hashimoto’s disease, a disorder of the thyroid. I learned that thyroid problems have been linked to gluten. Apparently, the molecular structure of gluten resembles that of the thyroid gland, so ingesting gluten may trigger an immune response that tells the body to attack the thyroid. Or so the theory goes.

So the nutritionist suggested I stop eating products with gluten and see whether my thyroid function improved. I honestly can’t tell if avoiding gluten has had any impact on the thyroid, but I do know it has led to many other positive changes.

For one, my joints began to feel a lot better. Gluten is said to cause inflammation; in my gluten-free travels, I have met people with arthritis who told me their symptoms disappeared after they stopped ingesting gluten, as presumably the inflammation went away. I don’t have arthritis, but I do exercise regularly and used to have to take a day off in between workouts because my joints were sore. Now I don’t experience that — I can go to the gym every day and feel OK.

My digestion also improved. One of the symptoms of low thyroid is digestive problems, especially constipation. On my new gluten-free regimen, this is never a problem. I also noticed that when allergy season came around this year, I didn’t get the sniffles, as I usually do. And, I began to feel a lot more energetic.

How do I manage food-wise? Well, I discovered a whole new world of wonderful gluten-free products. And I check restaurant menus online before I go out to dinner to make sure there is something there I can eat. I bring my favorite gluten-free crackers, nuts and other snacks to parties just in case there’s nothing on the table for me. I have even brought Tamari, a gluten-free soy sauce, to Chinese restaurants, some of which will prepare gluten-free meals for me. I have to admit that the moments that challenge me most are at restaurants that serve delicious breads before the main meal; it’s hard to stare those breads in the face when you’re hungry.

I’ve learned to avoid most desserts. I know I can always go home and eat a piece of chocolate or nibble on my favorite flour-free chocolate cake, which I often keep on hand for such emergencies. And honestly, I stick with this plan in part because it’s a great weight-control method. When presented with a vast array of gluten-filled tempting treats, I just look the other way. I just remind myself how good I feel.

Previously: Using your cell phone to test for food allergens, A discussion on going gluten-free, From frustration to foundation: Embracing a diagnosis of celiac disease and Guest post: Flying the friendly skies while navigating the challenges of eating gluten-free
Photo by Whatsername

If you give laboratory mice the fodder to make a home, they’ll not only be happier but also save you a lot of money in the bargain.

Joseph Garner, PhD, a mouse admirer and advocate, has found that giving mice the simple means to build a cozy little nest helps the animals warm themselves and produce more, healthier pups. For the small cost of nesting material – 62 cents a cage – mice will reproduce babies worth several thousand times that amount within six months, he and colleagues found in a recent study.

“I think that’s a pretty good return on investment,” Garner told me. Garner is an associate professor of comparative medicine at Stanford who’s been studying animal welfare for more than two decades.

He notes that laboratory mice are kept in cold conditions because it suppresses their aggressive tendencies. But as the mice labor to warm themselves, it changes their physiology – and the outcome of valuable experiments. That may be one reason, Garner theorizes, that so many drugs tested in mice end up not working in people.

In a previous study, he and fellow researchers found that if mice are supplied with shredded paper, they’ll build a comfortable little nest that allows them to naturally regulate their temperatures. Nest-building also helps the animals decrease their stress and anxiety levels, he says. Now, he and colleagues find that nest-building is also very cost-effective and could save laboratories many thousands of dollars. In their latest study, nude mice (so-called because they have no fur) that were provided with nesting material produced significantly more pups, and more of the pups survived in the warmer environment.

Continue Reading »

When the International AIDS Conference was held in Washington, D.C. this summer, it cast a spotlight on the U.S. epidemic, which continues apace. Every year, there are some 50,000 Americans newly diagnosed with HIV – a figure Anthony Fauci, MD, the nation’s top AIDS doctor, has called “embarrassing.”

To help contain the epidemic, which affects an estimated 1.2 million Americans, the U.S. Preventive Services Task Force today issued a new draft recommendation that urges everyone in the country – adolescents and adults between 15 and 65 – to get an HIV test. The task force has recommended screening in the past but only among those considered at increased risk. And the federal Centers for Disease Control also has advised routine voluntary screening, but has allowed people to opt out.

We think it’s important for everyone to screen once because treatment helps people live longer, healthier lives and also prevents transmission to others

Doctors and patients may be reluctant to test because they don’t see a reason to do so or are afraid to broach a topic that still carries a lot of stigma. But there are as many as 250,000 people in this country who are HIV-positive and don’t even know it. They could benefit from treatment - and so could the rest of the population, if this epidemic is to be brought under control.

“We think it’s important for everyone to screen once because treatment helps people live longer, healthier lives and also prevents transmission to others,” task force member Douglas K. Owens, MD, a professor of medicine at Stanford, told me.

In recent years, the science of AIDS has advanced to the point where it’s clear that early testing and treatment can make a big difference. People who are diagnosed early – even before symptoms show up – and then receive antiretroviral treatment can reduce their odds of getting serious AIDS-related complications. And a landmark study also has shown that treatment drives down the amount of circulating virus in a person’s blood to the point where the infected person is significantly less likely to pass the virus on to others.

Also, once people know their HIV status, they are more likely to take steps to reduce the risks of transmission, such as using condoms, studies have shown. All these factors, taken together, point to the need for a universal testing program, Owens says.

Previously: International AIDS conference ends on an optimistic note and National HIV screening and testing could be very cost-effective

I’ve been in the medical writing business for about 25 years, and there are few issues that have been as contentious as one I tackled recently for my article in Stanford Medicine magazine – the PSA test for prostate cancer. It is understandably an emotional issue for men, as it deals with an insidious disease that is responsible for 28,000 deaths a year. No man wants to hear that he has prostate cancer. But the question is, is the PSA a truly useful way for men to learn their status?

The perspectives on both sides could not be more divergent. Some argue the PSA, which is not a very precise test, represents a classic case of overscreening – an overused test that adds millions in unnecessary health care costs. Many men whose PSA numbers are high may not have cancer at all or a cancer so benign that it does not demand treatment, critics say. And yet those men, fearing the worst, may opt for treatments that can cause them permanent harm, such as impotency or incontinence. For that reason, the U.S. Preventive Services Task Force (USPSTF) has strongly recommended against the test, saying it causes more harm than good.

On the other side are those who believe the PSA is still a worthwhile tool, a good predictor of who is likely to develop the disease, particularly aggressive disease. In the two decades since it’s become widespread, they note, more men with advanced disease have been spared from death. One reader also criticized the USPSTF’s methodology, saying the group used faulty statistics to overstate the harms of screening.

James Brooks, MD, a professor of urology at Stanford and expert on prostate cancer, takes a middle ground. He believes the test is an indicator of risk, just as a blood pressure test is an indicator of risk for heart disease. But he doesn’t press his patients to pursue treatment just because their PSA numbers seem questionable at first, especially if a biopsy suggests they have low-grade disease; rather, he encourages those to consider active surveillance, in which the cancer can be regularly monitored.

There is one point on which both sides agree: It’s important for men to make informed decisions. Men should talk to their doctors before they get tested and if they do, spend some quality time afterwards discussing the results before they pursue treatment. And the other point of agreement: We need better tests.

Previously: The money crunch: Stanford Medicine magazine’s new special report, Ask Stanford Med: Answers to your questions on prostate cancer and the latest research and To screen or not to screen? When it comes to prostate and breast cancers, that’s still the question

A nonprofit started by Stanford graduates is gearing up to test its latest low-cost prosthetic – the ReMotion JaipurKnee – which is designed for amputees who live on $4 a day or less.

The knee prosthesis will be fitted to 1,000 patients in Latin America and Southeast Asia to make sure it works as hoped. D-Rev (Design Revolution), designer of the device, ultimately hopes to have it available in clinics across the globe.

“Mobility is synonymous with independence and opportunity, and they suffer, too, when a person loses a limb,” Vin Narayan, the company’s product manager, told me. “With the Re-Motion JaipurKnee, D-Rev combines user-centric design with our partners’ local expertise to give amputees around the world a chance to get back their mobility, as well as the independence and opportunities they’ve lost.”

The move to create a low-cost prosthetic for use in the developing world started with a graduate student project at Stanford in 2008. Students Joel Sadler, Eric Thorsell and two others designed the first JaipurKnee for use in India. The invention was named one of the Time magazine’s 50 Best Inventions of 2009.

The project took off and the students joined with Narayan to start a company to develop the prosthetic, which was initially field-tested in 3,500 people. The group has significantly refined the prosthetic and launched the 1,000 Knees Campaign to fund clinical trials of the latest version. Testing begins in 2013.

The company is partnering with local clinics to fit amputees with the knees and collect data on fit, training, user reaction and distribution. The prosthetics will initially be supplied to clinics free of charge, but once available on the market, the device’s target price will be $80. Users, however, will only pay what they can afford.

Previously: Biotech start-up builds artful artificial limbs
Photo by ReMotion JaipurKnee

Less than 10 years ago, I remember hearing French virologist Francoise Barre-Sinoussi, PhD, winner of a Nobel Prize for co-discovering the virus, express deep pessimism about whether it would be possible to develop an AIDS vaccine, the holy grail of the epidemic.

But as Barton Haynes, MD, director of the Duke Human Vaccine Institute, said at the International AIDS Conference today, the field of vaccine research is enjoying a revival, with hopes renewed, thanks to a series of new developments in just the last few years.

“I can assure you the HIV vaccine field is invigorated. We are treating this problem as a global emergency,” said Haynes, who has been working in the field for 27 years and leads the NIH’s Center for HIV/AIDS Vaccine Immunology.

One of the challenges of vaccine development is that HIV is an extraordinarily diverse virus, changing its character every time it replicates. An infected person may harbor hundreds of thousands or millions of different variations of the virus. So a vaccine needs to generate an immune reaction that is clever enough to recognize all of these variants.

I can assure you the HIV vaccine field is invigorated.

Vaccine researchers were encouraged in their quest by the results of a trial among 16,000 people in Thailand, reported in 2010, which showed a 31 percent reduction in infections. The vaccine was all too limited in its effectiveness, but it nonetheless pointed the way forward.

Since then, researchers have been following some of the trial participants and identified some immune “correlates” - clues on what it is about the immune response that can help predict whether a vaccinated person will be protected or not, Haynes said.

At the same time, scientists have identified several potent new neutralizing antibodies with broad ability to recognize different viral strains, Haynes said. These can be combined with so-called adjuvants, which boost the immune response, to form the basis for new clinical trials.

Haynes likened the struggle for a vaccine to the global arms race: Every time a weapon is introduced, a new, more powerful one is built. In HIV, every time an antibody attacks a virus in the body, a new “escape” virus is created, and HIV wins.

Now, he said, “We hope to create the human HIV arms race with a vaccine and a strong adjuvant so the vaccinee wins.”

Ruthann Richter is a Scope contributor and writer in the medical school’s communication office. She is attending the International AIDS Conference in Washington, D.C. and is posting periodic updates on the happenings there. You can see all of her updates in our HIV/AIDS category.