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For HIV, Treatment is Prevention

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U=U

For almost four decades, researchers have worked tirelessly to find a cure for the human immunodeficiency virus (HIV), which causes AIDS. There’s still more work to do, but a recent commentary published in JAMA [1] by Anthony Fauci, director of NIH’s National Institute of Allergy and Infectious Diseases, and his colleagues serves as a reminder of just how far we’ve come. Today, thanks to scientific advances, especially the development of effective antiretroviral therapy (ART), most people living with HIV can live full and productive lives. These developments have started to change how our society views HIV infection.

In their commentary, the NIH scientists describe the painstaking research that has now firmly established that people who take ART daily as prescribed, and who achieve and maintain an undetectable viral load (the amount of HIV in the blood), cannot sexually transmit the virus to others. To put it simply: Undetectable = Untransmittable (U=U).

The U=U message was introduced in 2016 by the Prevention Access Campaign, an international health equity initiative that aims to help end the HIV epidemic and HIV-related social stigma. The major breakthrough in combination ART regimens, which successfully reduced viral loads for many HIV patients, came over 20 years ago. But their importance for HIV prevention wasn’t immediately apparent.

There’d been some hints of U=U, but it was the results of the NIH-funded HIV Prevention Trials Network (HPTN) 052, published in The New England Journal of Medicine [2] in 2011, that offered the first rigorous clinical evidence. Among heterosexual couples in the randomized clinical trial, no HIV transmissions to an uninfected partner were observed when ART consistently, durably suppressed the virus in the partner living with HIV.

The data provided convincing evidence that ART not only treats HIV but also prevents the sexual transmission of HIV infection. The public health implications of what’s sometimes referred to as “treatment as prevention” were obvious and exciting. In fact, the discovery made Science’s 2011 list of top 10 Breakthroughs of the Year .

Three subsequent studies, known as PARTNER 1 and 2 and Opposites Attract, confirmed and extended the findings of the HPTN 052 study. All three showed that people with HIV taking ART, who had undetectable HIV levels in their blood, had essentially no risk of passing the virus on to their HIV-negative partners.

Of course, the success of U=U depends on people with HIV having the needed access to health care and taking their medications as prescribed every day of their lives [3]. ART works by preventing the virus from making more copies of itself. It’s important to note that achieving an undetectable viral load with treatment can take time—up to 6 months. Viral load testing should be performed on a regular basis to ensure that the virus remains at undetectable levels. If treatment is stopped, the virus typically rebounds within a matter of weeks. So, strict adherence to ART over the long term is absolutely essential.

Practically speaking, though, ART alone won’t be enough to end the spread of HIV, and other methods of HIV prevention are still needed. In fact, we’re now at a critical juncture in HIV research as work continues on preventive vaccines that could one day bring about a durable end to the pandemic.

But for now, there are more than 35 million people worldwide who are HIV positive [4]. With currently available interventions, experts have predicted that about 50 million people around the world will become HIV positive from 2015 to 2035 [5]. Work is proceeding actively on the vaccine, and also on ways to totally eradicate the virus from infected individuals (a “cure”), but that is proving to be extremely challenging.

Meanwhile, with continued advances, including improved accessibility to testing, adherence to existing medications, and use of pre-exposure prophylaxis (PrEP) in high risk individuals, the goal is to reduce greatly the number of new cases of HIV/AIDS.

References:

[1] HIV Viral Load and Transmissibility of HIV Infection: Undetectable Equals Untransmittable. Eisinger RW, Dieffenbach CW, Fauci AS. JAMA. 2019 Jan 10.

[2] Prevention of HIV-1 infection with early antiretroviral therapy. Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, Kumarasamy N, Hakim JG, Kumwenda J, Grinsztejn B, Pilotto JH, Godbole SV, Mehendale S, Chariyalertsak S, Santos BR, Mayer KH, Hoffman IF, Eshleman SH, Piwowar-Manning E, Wang L, Makhema J, Mills LA, de Bruyn G, Sanne I, Eron J, Gallant J, Havlir D, Swindells S, Ribaudo H, Elharrar V, Burns D, Taha TE, Nielsen-Saines K, Celentano D, Essex M, Fleming TR; HPTN 052 Study Team. N Engl J Med. 2011 Aug 11;365(6):493-505.

[3] HIV Treatment (U.S. Department of Health and Human Services)

[4] HIV/AIDS (World Health Organization)

[5] Effectiveness of UNAIDS targets and HIV vaccination across 127 countries. Medlock J, Pandey A, Parpia AS, Tang A, Skrip LA, Galvani AP. Proc Natl Acad Sci U S A. 2017 Apr 11;114(15):4017-4022.

Links:

HIV/AIDS (National Institute of Allergy and Infectious Diseases/NIH)

Treatment as HIV Prevention (NIAID)

Prevention Access Campaign

Anthony S. Fauci (NIAID)

HIV Prevention Trials Network (Durham, NC)


‘Tis the Season for Good Cheer

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Whether it’s Rockefeller Center, the White House, or somewhere else across the land, ‘tis the season to gather with neighbors for a communal holiday tree-lighting ceremony. But this festive image has more do with those cups of cider in everyone’s hands than admiring the perfect Douglas fir. What looks like lights and branches are actually components of a high-resolution map from a part of the brain that controls thirst.

The map, drawn up from mouse studies, shows that when thirst arises, neurons activate a gene called c-fos (red)—lighting up the tree—indicating it’s time for a drink. In response, other neurons (green) direct additional parts of the brain to compensate by managing internal water levels. In a mouse that’s no longer thirsty, the tree would look almost all green.

This wiring map comes from a part of the brain called the hypothalamus, which is best known for its role in hunger, thirst, and energy balance. Thanks to powerful molecular tools from NIH’s Brain Research through Advancing Innovative Technologies (BRAIN) Initiative, Yuki Oka of the California Institute of Technology, Pasadena, and his team were able to draw detailed maps of the tree-shaped region, called the median preoptic nucleus (MnPO).

Using a technique called optogenetics, Oka’s team, led by Vineet Augustine, could selectively turn on genes in the MnPO [1]. By doing so, they could control a mouse’s thirst and trace the precise control pathways responsible for drinking or not.

This holiday season, as you gather with loved ones, take a moment to savor the beautiful complexity of biology and the gift of human health. Happy holidays to all of you, and peace and joy into the new year!

Reference:

[1] Hierarchical neural architecture underlying thirst regulation. Augustine V, Gokce SK, Lee S, Wang B, Davidson TJ, Reimann F, Gribble F, Deisseroth K, Lois C, Oka Y. Nature. 2018 Mar 8;555(7695):204-209. 

Links:

Oka Lab, California Institute of Technology, Pasadena

The BRAIN Initiative (NIH)

NIH Support: National Institute of Neurological Disorders and Stroke


Zooming In on Meiosis

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Meiosis

Credit: Simone Köhler, Michal Wojcik, Ke Xu, and Abby Dernburg, University of California, Berkeley

Meiosis—the formation of egg and sperm cells—is a highly choreographed process that creates genetic diversity in all plants and animals, including humans, to make each of us unique. This kaleidoscopic image shows cells from a worm exchanging DNA during meiosis.

You can see a protein-based polymer tether (green) from what’s called the synaptonemal complex. The complex holds together partner chromosomes (magenta) to facilitate DNA exchange in nuclei (white). Moving from left to right are views of the molecular assembly that progressively zoom in on the DNA, revealing in exquisite detail (far right) the two paired partner chromosomes perfectly aligned. This is not just the familiar DNA double helix. This is a double helix made up of two double helices!


A Microbial Work of Art

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Sclupture of a bacterial colony

Credit: Scott Chimileski, Sylvie Laborde, Nicholas Lyons, Roberto Kolter, Harvard Medical School, Boston

Bacteria are single-celled organisms that are too small to see in detail without the aid of a microscope. So you might not think that zooming in on a batch of bacteria would provide the inspiration for a museum-worthy sculpture.

But, in fact, that’s exactly what you see in the image. Researchers grew in a lab dish Bacillus licheniformis, a usually benign bacterium from the soil that produces an enzyme used in laundry detergent. The bacteria self-organized into a sand dollar-like pattern to form a cohesive structure called a biofilm. The researchers then took a 3D scan of the living bacterial colony in the lab and used it to print this stainless steel sculpture at 12 times the dime-sized biofilm.


A Scientist and Conservation Photographer

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These stunning images of animals were taken by Susan McConnell, whose photographs have appeared in Smithsonian Magazine, National Geographic, Nature’s Best Photography, Africa Geographic, and a number of other publications. But photography is just part of her professional life. McConnell is best known as a developmental neurobiologist at Stanford University, Palo Alto, CA, and an elected member of the U.S. National Academy of Sciences.

How did McConnell find the time while tracing the development of the brain’s biocircuitry to launch a second career as a nature photographer? Her answer: Every research career has its seasons. When McConnell launched her lab in 1989 at the age of 31, she was up to her eyeballs recruiting staff, writing research grants, and pursuing many different leads in her quest to understand how neurons in the brain’s cerebral cortex are produced, differentiated, and then wired together into functional circuits.


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