Rather than destroying HIV, a proposed treatment would embrace its infectious abilities, sending the virus into competition with a harmless, stripped-down version of itself.

Dubbed therapeutic interfering particles, or TIPs, these engineered viral scraps would ride with HIV as it spreads from person to person. By out-competing HIV for cellular resources, the TIPs might slow its progression and lower infection rates.

"A virus can't replicate without a host, and similarly TIPs can't replicate without HIV. It would piggyback on the virus," said biophysicist and virologist Leor Weinberger of the University of California, San Diego, who modeled the epidemiology of TIPs in a study March 17 in PLoS Computational Biology. "It's basically a virus of a virus."

Approximately 33 million people now carry HIV, or human immunodeficiency virus, which infects immune system cells that defend against disease. The virus gradually destroys them, taking away the body's ability to protect itself. Without treatment, HIV infection leads to AIDS in about 10 years. Death follows soon after as common diseases overcome the body.

First proposed in 2003 and tested in cell cultures, Weinberger’s TIPs are HIV’s genetic code stripped down to one-third its original size. TIPs lack crucial pieces that allow self-replication, and copy themselves by sneaking into HIV's genetic code and multiplying when it does.

TIPs also contain some HIV-inhibiting sequences and compete for the same virus-building proteins as HIV. As a consequence, TIPs may slow the replication of infectious HIV, fending off AIDS for an extra 5 to 10 years.

Although TIPs have not left the lab and don't represent a cure, Weinberger said they would complement other treatments, including widely used anti-retroviral therapies. By reducing the HIV load in an infected person, TIPs could also reduce the chances it will spread.

To see how TIPs would affect population-wide infection rates, Weinberger's team built a computer model based on their laboratory data and disease data for sub-Saharan Africa, the worst-afflicted region in the world, with HIV prevalence rates in some countries at over 30 percent.

Even in a pessimistic scenario, where TIPs are only partially effective, giving 1 percent of HIV-infected people a TIP treatment dropped HIV prevalence from 29 percent to 6.5 percent after 50 years. A more optimistic simulation of TIP efficacy chiseled HIV prevalence down to 1 percent within 30 years. By comparison, a hypothetical half-protective vaccine given to 95 percent of people only lowered prevalence to 18.7 percent after 50 years.

According to Weinberger, the TIP treatment would get around the problem of "superspreaders," such as drug users and sex workers, who are responsible for a disproportionately large amount of HIV infection. These people are often hard to identify, difficult to reach and apt to refuse treatment. By spreading silently through populations at risk for HIV, TIPs would eventually reach them.__

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However, much remains to be done before TIPs in people are more than hypothetical.

"The concept and computational model are intriguing, but I'd like to see a clear demonstration of this in animal models," said computational biologist Allen Rodrigo of Duke University, who wasn't involved in the study. "So far, it has been almost impossible to design a strategy that HIV can't escape from."

Weinberger argued that even if HIV evolves to escape TIPs, TIPs would adapt to chase HIV. The engineered virus could compete for decades before being outpaced or reverting back into HIV, he said.

Rodrigo also questioned the risk in a treatment that relies on a rapidly evolving virus to spread. The piggybacking TIPs could mutate to form a new and different virus. "Mixing of the genetic material is something to be concerned about. We still don't know much about how that works," Rodrigo said.

Another concern is public perception of a treatment strategy that relies on infection. Doctors and public health officials are accustomed to fighting HIV, not spreading parasites of the virus, and patients may be distrustful.

"This study is all about seeing if it's worth putting money and effort into studying TIPs, or if they're a waste of time. Our conclusion is that it looks like they're worth going after," Weinberger said. "If optimized, they could have an enormous effect."

Images: 1) 3-D model of the human immunodeficiency virus./Visual Science Company. 2) Sub-Saharan HIV prevalence modeled after the start of several therapies including TIP treatment, hypothetical vaccines, and anti-retroviral therapy (ART). Photo: Weinberger et al./PLoS Computational Biology.

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Citation: "Autonomous Targeting of Infectious Superspreaders Using Engineered Transmissible Therapies." Vincent Metzger, James Lloyd-Smith, Leor Weinberger. PLoS Computational Biology, Vol. 7, Issue 3, March 17, 2011. DOI: 10.1371/journal.pcbi.1002015