This week, HIV research made headlines with several independent studies from scientists around the country. One warns of increasing stroke rates for people infected with HIV, while another two point toward new potential treatment drugs.
1. Stroke rate rises for patients with HIV
First, the bad news. Patients infected with HIV are up to three times more likely to suffer a stroke – the third leading cause of death in the US.
Bruce Ovbiagele of the University of California at San Diego and colleagues reviewed a national set of data from all hospital patients diagnosed with stroke between 1997 and 2006.
While the overall hospitalization rate for stroke declined, they found that stroke diagnoses among HIV-infected patients rose 67%. Specifically, they suffered ischemic strokes caused by impaired blood flow to the brain due to clots.
This increase coincided with the widespread use of highly active antiretroviral therapy (HAART) by HIV patients. "The rise in HIV stroke rate may simply be because patients are living longer," Ovbiagele says. “After 55, the risk doubles for each successive decade."
But he also notes that these drugs are associated with complications linked to higher stroke risks – such as cholesterol and glucose levels.
"Patients on HAART will clearly need to remain on the drugs to extend their lives,” Ovbiagele says, “but the challenge will be to clarify whether HAART therapy is an innocent bystander or a direct culprit in this process.”
Overall, the risk for stroke remains low, but patients on these drugs should be aware that stroke is "highly preventable," Ovbiagele says, and should work with their doctors to keep their weight and cholesterol levels under control.
Scientists have mapped out the structure of the HIV ‘capsid’ – the protein container that delivers HIV’s genetic material to human cells. Understanding the capsid will provide a roadmap for developing drugs to disrupt its formation and prevent HIV infection.
When the virus binds to healthy cells, the cone-shaped capsid is delivered into the cell. Once inside, the capsid comes part and releases viral genetic material. That’s how HIV gets the cell to make copies of its genes and proteins.
As new viruses are made, the genetic material is packaged into rounded, immature capsids that HIV uses to flee the infected cell. But before these newly released viruses can infect other cells, the immature capsid must mature into the cone-shaped shell.
If formation of the mature capsid is disrupted, the virus is no longer infectious.
So Mark Yeager and colleagues from the University of Virginia School of Medicine and Scripps Research Institute examined the atomic structures of the cone and created a complete atomic model of the HIV capsid (pictured). The researchers plan to refine the model to identify possible ‘weak’ points they can target using newly designed drugs.
3. Missile-like molecules invade HIV
Molecules made of RNA can seek out and attack cells infected with HIV – in mice.
These molecules are called small interfering RNAs (siRNAs). They’re short, double-stranded RNA molecules that can interfere with the actions of certain genes.
A team led by John Rossi from Beckman Research Institute of the City of Hope and Ramesh Akkina from Colorado State University made the siRNA more effective by adding it onto another short RNA molecule known as an ‘aptamer.’
The combined molecule is like a guided missile they call a ‘chimera.’ The new addition whizzes to the HIV-infected cell and delivers the siRNA. That way, "you're only targeting what has to be targeted,” Rossi explains.
Using infected mice, the team showed that a single injection caused a sharp drop in HIV concentrations in the blood. Several weekly injections completely protected the mice from the decline of immune cells.
The researchers say it could help patients who developed resistance to HIV drugs. But because the chimera doesn't kill infected cells, it won't cure HIV. The next step, Rossi says, is to use the chimera to deliver siRNAs that can kill infected cells and “start purging the infected cell population.”
Image: Owen Pornillos, Barbie Ganser-Pornillos, Kelly Dryden, and Mark Yeager