News

August 19, 2010

New Strategy Could Eradicate Latent HIV-Infected Cells

Researchers report that they have taken the first step toward killing cells that are latently infected with HIV—cells that serve as a reservoir of persistent HIV reproduction and that current antiretroviral (ARV) drugs can’t reach. Their findings have been accepted by the open-access journal AIDS Research and Therapy.

Combination ARV therapy is incredibly potent. Numerous studies have shown that the therapies in widest use today can suppress all but the tiniest amount of HIV. However, the miniscule amount of HIV that remains—likely coming from reservoirs, such as resting CD4 cells, that aren't always reached by ARV therapy—can completely reseed the body with virus as soon as a person stops taking his or her treatment.

Those resting cells have snippets of HIV DNA integrated into their own DNA, but they aren’t actively making new virus. Unfortunately, ARVs don’t affect cells that aren’t actively reproducing, and the amount of HIV DNA in the CD4s is so small that it doesn’t trigger the cell’s natural self-protection mechanism, which causes cells to self-destruct when their DNA gets altered too much.

Now, a group of Israeli researchers believes they have developed a method for getting to those latent cells and killing them. The group, led by Abraham Loyter, PhD, of Hebrew University in Jerusalem, is looking at ways to force the virus to integrate in multiple places in the cell’s DNA, triggering the cell’s chemical panic button and causing it to kill itself, a process called apoptosis.

Loyter and his colleagues developed two chemicals—dubbed INS and INrs peptides—that can prompt this process and combined them with an experimental protease inhibitor. The group then treated HIV-infected human immune cells for two weeks with the compounds, which they called the “mix.” Loyter’s group then allowed the remaining cells to grow out for an additional two weeks. HIV DNA levels were measured at three time points: before treatment with the mix, after two weeks of treatment, and then again two weeks after treatment was stopped.

Loyter’s team found that the “mix” worked as they’d hoped. After two weeks of treatment with the combination, no HIV DNA could be found, and this remained the case for an additional two weeks after the last dose of the treatment was added to the cells. The authors caution it is possible that some residual integrated HIV DNA was still present in the cells. Nevertheless, their results are encouraging.

“Stimulation of viral integration by the INS and INrs peptides, combined with the prevention of virion production by the protease inhibitor, not only resulted in blocking of HIV-1 infection but also in extermination of the infected cells by invoking apoptosis,” the authors concluded.

“Whilst this research is promising, a major caveat with these studies is that they are preliminary,” Loyter cautioned. “So far these experiments have only been shown to ‘cure’ HIV from small dishes of cultured cells in the authors’ laboratory, but the findings are an exciting development in the quest to eradicate this devastating global pandemic.”

August 23, 2010

Two Approved Cancer Drugs Fight HIV

August 20, 2010

New HIV Microbicide Candidate Has Unique Properties

An experimental HIV entry inhibitor might be particularly well suited for use as a preventive microbicide—due to the area of the virus it targets and its potential to avoid being quickly broken down by the body. Scientists announced their findings about the drug, which is still in early development, on August 18 in an online article in the journal Virology.

Encouraging HIV prevention news was recently shared at the International AIDS Conference in Vienna, where researchers reported a study involving a microbicidal tenofovir gel that protected nearly 40 percent of females users it from HIV infection. In women who used the gel most frequently, the protective effect exceeded 50 percent.

There is a downside to the tenofovir gel, however. The drug in its oral form (as Viread, Truvada or Atripla) is one of the most widely used HIV treatments in developed countries. This poses two problems. First, the gel might not be protective if the HIV-positive sex partner carries a tenofovir-resistant strain of the virus. Second, there’s a small chance that if a person becomes infected with HIV and continues using the gel, the virus could develop resistance to tenofovir, which would remove that drug from the person’s list of treatment options. Thus, researchers are looking for other drugs that could be incorporated into microbicides.

Brett Welch, PhD, from the University of Utah, and his colleagues have found a new microbicidal candidate, called PIE12-trimer. The drug is made up of three D-peptides: long chains of proteins designed to block a pocket on the outside coat of HIV.

Because the PIE12-trimer binds to an HIV pocket that doesn’t readily mutate, Welch’s group is hoping that HIV will be less likely to become resistant to the drug. What’s more, D-peptides are sturdy, hence they will likely have a longer therapeutic effect in the body than other peptides.

Studies so far have only occurred in cells in the lab, but Welch and another University of Utah colleague, Debra Eckert, PhD, have formed a company called Kayak Bioscience to develop the drug for human testing.

Though the authors state that the drug could theoretically work as a treatment for HIV, most current peptide drugs must be injected because they can’t survive the passage from the gut to the blood stream. This doesn’t necessarily kill PIE12-trimer’s chances as a treatment for HIV—if it only has to be injected weekly or monthly, people might not mind it—but does give it a higher hurdle to jump over.