For the approximately 37 million people worldwide who are infected with the Human Immunodeficiency Virus, HIV, the newest cocktails of anti-retroviral drugs have come a long way in beating back the retrovirus and keeping an infection in check. Still, those drugs are no cure.
While the treatments snarl the viral assembly line and thwart new infectious particles from invading the body’s cells, HIV itself is still there, hunkered in the DNA of a patient’s genome until there is an opportunity for a comeback—say, when a patient goes off their medication.
As long as there is lingering HIV, patients must keep taking the drugs, which cause side-effects, make for high prescription bills, and raise the threat of drug resistance. At least, that is the case for now. In a new study, scientists reveal a possible way to literally hack those lurking viruses out of a person’s DNA strands.
With a custom enzyme made through coerced evolution, researchers selectively and reliably sliced HIV sequences from a number of cell types: bacteria, human cell lines used in research, in cells collected from patients with HIV infections, and in “humanized” mice with HIV. Though the strategy is early in development—far from clinical use—the data so far points to an effective and safe way to help drug treatments completely finish off HIV infections. This is a “promising strategy for future clinical applications,” the authors report.
The method relies on an enzyme that researchers forced into targeting a highly conserved, 34-base sequence of genetic code that flanks HIV genomes when they’re lodged in human DNA (these implanted sequences are called proviruses).
Of course, not every HIV provirus has these 34-base sequences—but most of the ones infecting humans do. The sequence, found in most HIV-1 subtypes, is estimated to occur in 82 percent of individuals infected with HIV.
The HIV-targeting enzyme, dubbed Brec1 (for broad range recombinase 1), originally sought out and snipped a completely different genetic sequence. But the researchers coaxed it into chopping HIV by making mutated versions. Then, researchers screened the mutants for the ability to cut sequences related to the conserved HIV sequence. Then, they repeated the process, gradually shifting the target sequence until it matched HIV.
With each cycle, the researchers would fish for a mutated version of the enzyme that got closer and closer to cutting the specific string of genetic bases in the HIV provirus. After 145 cycles, they had Brec1 that cut the exact provirus sequence and only that exact sequence.
Once Brec1 slashes the flanking HIV sequence, the whole provirus gets extracted and trashed. Then the enzyme patches up the DNA break it’s created.
There are other genetic scissors that researchers can use to cut out specific genetic elements, such as proviruses. Most notably, there is ZFN, TALEN and CRISPR. But those methods can accidentally cut non-target genetic sequences, a dangerous possibility in living humans. And they don’t patch up their cut, leaving damage that can trigger cells’ emergency DNA repair systems, creating other cellular mayhem. Brec1 so far seems to avoid both of those problems.
In lab tests, researchers found that Brec1 could cut the HIV sequence out of every cell type they tested. And, the enzyme worked to carve out HIV without any toxic or genetic side effects, the researchers carefully noted.
They also reported success in mice, specifically “humanised” mice. The researchers engineered the animals to carry human immune cells that can be infected with HIV. Given a dose of Brec1—delivered via a genetically hollowed out, harmless virus—HIV infection in the mice declined over time to the point where HIV was no longer detectable, even though uninfected human cells persisted in the animals.
If the result holds up in humans, the enzyme may finally offer a solution to lingering HIV infections in patients on drug treatments. “Complete elimination of replication-competent HIV, including latent viral reservoirs, may be the only way to achieve a genuine cure,” the authors conclude.
Nature Biotechnology, 2015. DOI:
• Nearly 37 million people are now living with HIV.
• 2.6 million are under the age of 15.
• In 2014, an estimated 2 million people were newly infected with HIV.
• 220,000 were under the age of 15.
• Every day about 5,600 people contract HIV—more than 230 every hour.
• In 2014, 1.2 million people died from AIDS.
• Since the beginning of the pandemic, nearly 78 million people have contracted HIV and close to 39 million have died of AIDS-related causes.
• As of March 2015, around 15 million people living with HIV (41% of the total) had access to antiretroviral therapy.
The Regional Picture
More than two-thirds (70 percent) of all people living with HIV, 25.8 million, live in sub-Saharan Africa—including 88 percent of the world’s HIV-positive children. In 2014, an estimated 1.4 million people in the region became newly infected. An estimated 790,000 adults and children died of AIDS, accounting for 66 percent of the world’s AIDS deaths in 2014.
Asia and the Pacific
In Asia and the Pacific, nearly 340,000 people became newly infected in 2014, bringing the total number of people living with HIV there to 5 million. AIDS claimed an estimated 240,000 lives in the region in 2014.
Approximately 13,000 people became newly infected in the Caribbean in 2014, bringing the total number of people living with HIV there to 280,000. AIDS claimed an estimated 8,800 lives in 2014.
There were an estimated 87,000 new HIV infections and 41,000 AIDS-related deaths in Latin America in 2014. This region currently has 1.7 million people living with HIV.
North Africa and the Middle East
Approximately 240,000 people are living with HIV in this region and an estimated 22,000 people became newly infected in 2014. An estimated 12,000 adults and children died of AIDS in 2014.
Eastern Europe and Central Asia
Some 140,000 people were newly infected with HIV in 2014, bringing the number of people living with HIV to 1.5 million. AIDS claimed 62,000 lives in 2014.
Western and Central Europe and North America
In 2014, there were 85,000 new cases of HIV, bringing the number of people living with HIV in Western and Central Europe and North American to 2.4 million. An estimated 26,000 people in these regions died of AIDS in 2014.
Source: UNAIDS Report: How AIDS changed everything, 2015; UNAIDS 2014 Global Statistics.