The National Institute on Drug Abuse is upgrading its use of proteomics to study how drug abuse affects the progression of HIV/AIDS.
Last month, the agency put out a notice seeking proposals for the creation of at least one center, and most probably two, that will use proteomics technologies to study changes at the protein level in individuals with HIV/AIDS who use illicit drugs.
Teams chosen for the grant will share $2 million per year for three years to create such a center or centers. The grant is being provided through a P20 mechanism. Unlike the traditional grant mechanism to fund creation of centers that use conventional and well-accepted methods and technologies, P20 grants are specifically to fund centers using newer, less-established technologies and techniques, such as proteomics.
NIDA had previously funded the creation of two centers, one at the University of Illinois at Urbana-Champaign and another at Yale University, that use proteomics tools to study the study and effects of drug abuse. It also has funded individual projects through R01 grants for researchers using proteomics technologies to study the intersection of HIV/AIDS and drug abuse. But the current grant is the biggest initiative the agency has taken to support such work.
While there has been extensive research done separately in HIV/AIDS and drug abuse, work looking at the link between the two is largely virgin territory. In fact, many studies on HIV/AIDS exclude patients who are characterized as drug abusers, said David Shurtleff, director of the division of basic neuroscience and behavioral research at NIDA.
Indeed, a search on PubMed using keywords such as “proteomics,” “HIV,” “cocaine,” “heroin,” “methamphetamine,” and “crack” brought up only two results dating back to when the database was created — despite knowledge that opioids such as heroin are known to increase some of the co-receptors for HIV/AIDS. In addition, some studies have suggested that abusing such drugs may change the properties of the blood-brain barrier and enable the HIV virus to enter the brain, Shurtleff said.
Evidence also suggests that some drugs of abuse may interact with the virus to further exacerbate symptoms of NueroAIDS, resulting in cognitive alterations and neurotoxicity in the brain.
“What we don’t yet completely understand is some of these protein changes that may be occurring [and] the mechanisms involved,” Shurtleff told ProteoMonitor last week. “And that’s what we’re hoping proteomics may shed some light on; these mechanisms that are involved in host response, immunity, drug-drug interactions — all these things that are likely to occur in patients who abuse drugs and have the virus.”
There has long been a link between HIV/AIDS and drug abuse. In the early days of the virus, sharing needles spread the virus between intravenous drug users. Most recently, crystal methamphetamine has been cited as a leading factor in transmission due to the drug’s ability to lower inhibitions and increase the chances of risky sexual practices.
According to the Centers for Disease Control and Prevention, 681,601 people contracted HIV through heterosexual and homosexual contact between the mid-1980s to 2005. That includes transmissions from sexual contact and IV-drug use. By comparison, 241,364 people contracted the virus during that period through IV-drug use alone.
“The proteomics will help us better understand the molecular mechanisms associated with HIV and drug abuse and may lead to diagnostic and prognostic indicators about how the virus is progressing in these particular patient populations, [and] may lead to new treatment approaches, a whole host of new related applications.”
In fiscal 2007, recognizing that HIV/AIDS and drug abuse are “intertwined epidemics,” Congress and the NIH’s Office of AIDS Research designated $300 million, or 30 percent of NIDA’s total budget, to study the link between the two according to NIDA.
“It’s an area [where] we don’t understand a lot about what happens when the drug abuse interacts with the virus,” said Shurtleff, who considers the use of proteomics technologies to specifically look at how HIV/AIDS interacts with drugs of abuse “a gap in our research portfolio at NIDA.
“We don’t understand how the virus may mutate. We don’t understand the host response to the virus in someone who’s exposed to drugs of abuse. We don’t understand, necessarily, the complex interactions between HAART [Highly Active Antiretroviral Therapy] and drug abuse that may be toxic,” Shurtleff said.
Proteomics, he said, will help NIDA better understand the molecular mechanisms associated with the link between the virus and drug abuse “and may lead to diagnostic and prognostic indicators about how the virus is progressing in these particular patient populations.” He added that the technology “may lead to new treatment approaches, a whole host of new related applications.”
Though the agency said it has no preference for the proteomics technology to be used at the prospective center, it expects the platforms to be “state of the art,” Shurtleff said. He added that the priority is to find someone with expertise in proteomics, rather than HIV/AIDS or drug abuse, to lead the work. The research team will be expected to include individuals with expertise in those two areas, however.
“So it’s really a good opportunity for people who were thinking this might be an interesting idea [but] wouldn’t know how to go about it,” Shurtleff said. “NIDA is providing sort of seed money [or] pilot funding to say, ‘Give it a try.’”
Applicants are expected to have proteomics core facilities and have at least three supporting research projects relevant to what the proposed center would be doing with the NIDA funding. For example, Shurtleff said, an individual could be doing research into HIV replication in drug-abusing populations using biological samples such as plasma, cerebrospinal fluid, or post-mortem brain tissue.
Similarly, the applicant could be using animal models as a way of looking at protein changes in combination with HIV and trying to translate those findings to humans.
Depending on what comes out of the effort after three years, the program may be extended or expanded, Shurtleff said. “But right now, we’re just trying to see what kinds of ideas the community has to address this complex problem,” he said.
Additional Information about the grant and the application process can be found here. Letters of intent are due Feb. 27 while the application is due March 27. The project start date is Sept. 15.
Shurtleff recommended that interested parties discuss their plans with program directors Diane Lawrence and Christine Colvis before applying in order to get a better handle on what NIDA is seeking.