Making HIV tests visible to the naked eye

One of the recurring themes in healthcare is that a lot of what works in the developed world doesn't work in the developing world. There may be limited access to basics like power or communications facilities, never mind the medical technologies that make a hospital one of the modern wonders of the world. Beyond simple access to expensive technologies and medicines, even something as basic as a diagnostic test might be too expensive or require skilled technicians to use.

Though cures might remain expensive—drug companies like their profits—every dime saved on diagnosis is a dime more for prevention and cure. That makes cheap, accurate, and simple diagnostic tests very, very desirable.

I was thinking about this when I came across an older paper that somehow didn't attract any attention when it came out. Last year, a group of researchers showed that they could detect HIV at extremely low concentrations. That by itself is nothing special: people are always improving diagnostic tests. What is special is that the test is very much like a pregnancy test, in that a simple visible color change indicates a positive result. Even better, it seems to work in real-life tests.

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Early treatment sometimes lets the body keep HIV in check

C. Goldsmith/UCLA

HIV, the virus that causes AIDS, belongs to a class of viruses that insert a copy of themselves into the genomes of the cells they infect. As long as some infected cells are alive, it is impossible to completely eliminate the virus. As a result, medical research has focused on two areas: vaccines that can prevent infection in the first place, and antiviral medications that keep the infection in check once it's established. Despite incredible successes in the development of antivirals, they'd still be needed for the rest of an infected individual's life, as a lapse could allow the virus to return from cells in which it had established a long-term infection.

Recently, however, came a report that early treatment with antivirals has allowed one individual to keep an HIV infection limited for extended periods of time without treatment. Now, a report in PLOS pathogens suggests that this case may not be as exceptional as we might have thought. In a small population of people treated immediately after infection, about 15 percent managed to keep the virus in check after they discontinued other treatments.

There have been a number of individuals who show a more complicated infection, one in which they never progress to full-blown AIDS. Many of these have a mutation in a gene that the virus uses to latch on to and enter cells. Bone marrow transplants using cells from people with this mutation have now been used in procedures that seem to have eliminated the virus from at least three individuals. Bone marrow transplants are drastic and carry risks (these patients needed them for other reasons), so this doesn't represent a general cure, but it did suggest that the virus might not necessarily get established widely in the body.

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Mississippi doctors “functionally cure” a toddler of HIV

Mississippi doctors are reporting they have "functionally cured" a two-year-old child of HIV, according to findings presented at the Conference on Retroviruses and Opportunistic Infections (CROI) today. "Functionally cured" in this scenario means the child is now without detectable levels of virus and has not demonstrated any signs of the disease after 10 months without antiretroviral therapy. It's the first well-documented case of such results in an infant and only the second person overall documented with a cure. The first occurred in 2012 as Timothy Brown, later known as "the Berlin Patient," was cured through a bone marrow stem transplant.

Research on the case is still on going, and it has not yet been determined whether these results can be replicated in clinical trials with other HIV-exposed children. The National Institute of Allergy and Infectious Diseases (NIAID) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)—both components of the National Institutes of Health—provided funding to support the analysis presented at CROI. The child remains under the medical care of Hannah Gay, M.D., a pediatric HIV specialist at the University of Mississippi Medical Center in Jackson.

When the child came back and showed no signs of HIV, Gay even thought it was a mistake. “My first thought was, ‘oh my goodness. We have been treating an uninfected child,” she told NBC News. "But I checked the records which confirmed she was, in fact, infected.”

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Compounds coax HIV out of hiding so it can be eliminated

HIV "buds" out of immune cells, like this T cell.

Dr. Tom Folks, NIAID

Chemists have built molecules that flush out human immunodeficiency virus (HIV) hiding inside immune cells. While these compounds do not cure the virus that causes AIDS, they could be a powerful addition to current treatments, which cannot eradicate these dormant viruses.

Current HIV treatment requires a cocktail of drugs to kill viruses replicating in T cells, and patients must regularly take their medicine to keep the virus at bay. HIV can hibernate in these cells and reemerge to infect patients if they stop treatment.

Another approach to treating HIV aims to reactivate these dormant viruses, thereby allowing the immune system (or the virus itself) to kill the cells where they are hidden. In conjunction with cocktail therapies that keep HIV under control, this approach has the potential to completely purge the virus from a patient.

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Fighting on after the war is over, HIV contrarian publishes yet another paper

When the world first learned of AIDS, there was a lot of justifiable confusion over what could cause such a confusing array of symptoms. But, over time, the confusion slowly subsided. A virus, HIV, was found that infected the right cells and spread in the right ways to explain the progression of the disease. Public health measures that targeted it slowed its spread, and drugs designed to target the virus helped extend the lives of those infected. By now, the Nobel Prizes have been awarded and the evidence that HIV causes AIDS is so comprehensive, it's treated as a fact.

But not by everyone. As attention first focused on HIV, a handful of scientists very publicly raised questions about whether the scientific evidence was as solid as others thought. And, years later, at least one's still at it: Berkeley molecular biologist Peter Duesberg. Last month, after his latest effort to see his arguments published ended up in a retraction and the firing of an editor-in-chief, Duesberg managed to get it published in the Italian Journal of Anatomy and Embryology.

It's a rather dramatic path to publication for a paper. But anyone familiar with Duesberg's sometimes flamboyant contrarian nature wouldn't be surprised.

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Researchers short-circuit the immune system to block HIV

So far, efforts to develop a vaccine against HIV have failed. It's not that they don't induce people to make antibodies against the virus—they make plenty of those—it's just that most of the antibodies don't usually keep the virus from infecting new cells. Nevertheless, these sorts of antibodies are possible to make. A number of patients that weren't vaccinated but fail to develop AIDS following HIV infection have been identified, and some of them are protected by antibodies that successfully neutralize many strains of HIV.

Since these broadly neutralizing antibodies are the sorts of things we want out of the vaccination process, a team of labs at Caltech and UCLA decided to short-circuit the need for a vaccination, or even antibody-producing immune cells. They created a disarmed adenovirus that contained the genes needed to produce a broadly effective antibody from humans, optimizing the DNA to make sure that the antibody was made in muscle cells, and then secreted into their environment.

The modified virus was then injected into mice that had had their immune systems humanized (the stem cells in their bone marrow were killed off and then repopulated with human cells). The mice were then exposed to levels of HIV many times higher than are normally present during initial infections. Not all antibodies effectively blocked new infections, but at least one did so consistently. The resistance to new HIV infections persisted for the life of the experiments.

The authors are clearly thinking that this isn't just a demonstration that will be limited to the lab, since they argue that "Our results suggest that successful translation of this approach to humans may produce effective prophylaxis against HIV." That translation may be challenging, however, as the use of these viruses in gene therapies has been somewhat mixed. Still, it seems like a promising idea, given that it could mean a one-time needle stick for lifelong protection.

Nature, 2011. DOI: 10.1038/nature10660 (About DOIs).