Overcoming cardiac pacemaker "source-sink mismatch"

Instead of complication-prone electronic cardiac pacemakers, biomedical engineers at Georgia Tech and Emory envision the creation of “biological Read more

Hope Clinic part of push to optimize HIV vaccine components

Ten years ago, the results of the RV144 trial– conducted in Thailand with the help of the US Army -- re-energized the HIV vaccine field, which had been down in the Read more

Invasive cancer cells marked by distinctive mutations

What does it take to be a leader – of cancer cells? Adam Marcus and colleagues at Winship Cancer Institute are back, with an analysis of mutations that drive metastatic behavior among groups of lung cancer cells. The findings were published this week on the cover of Journal of Cell Science, and suggest pharmacological strategies to intervene against or prevent metastasis. Marcus and former graduate student Jessica Konen previously developed a technique for selectively labeling “leader” Read more

AIDS

HIV discordant couples

On Thursday, NPR had a nicely done story on discordant couples (one partner is HIV positive, the other is HIV negative) in Kenya.

It provided a reminder of Susan Allen’s work in Rwanda and Zambia with discordant couples. It also very simply laid out the policy issues connected with treating discordant couples:

Medical workers are http://www.raybani.com/ extremely interested in discordant couples for two reasons. One is that almost half of new infections in Kenya happen in these relationships. It’s one place where HIV is spreading. The second reason is that when couples are open with each other about their HIV status, managing HIV is more successful…

The World Health Organization now recommends that any HIV-positive individual in a discordant relationship be supplied HIV treatment. But discordant couples are still being treated on an ad hoc basis in Kenya, primarily because the funding for the medication just isn’t there.

Allen’s research provided critical data about HIV Ray Ban outlet transmission and prevention methods, and led to the adoption of the WHO guidelines mentioned in the story. She has said that the WHO guidelines were designed to help partners in a stable relationship work together to prevent the uninfected person from getting the virus and that low-tech, inexpensive prevention methods like condoms are just as important as antiretroviral therapy in this effort.

Posted on by Quinn Eastman in Immunology Leave a comment

Fertility: a new frontier in treating those with HIV

HIV

Not long ago, physicians who treated those with HIV focused only on helping their patients stay well. Today some physicians are also beginning to focus on helping those patients conceive.

“Most of the patients who are now diagnosed with HIV are in their reproductive years, and as many as a third express a desire to have children,” says Emory reproductive endocrinologist Vitaly Kushnir, MD.

This emerging area of treatment has been made possible thanks to the growing effectiveness of a combination of drugs known as Highly Active Antiretroviral Therapy, or HAART, used for years to treat retroviruses, including HIV.

“Now that people with HIV are living longer, fertility and HIV is an emerging area of interest,” says Kushnir. “Several studies have indicated that HIV drugs if given early in the course of the disease can reduce the risk of transmission from an HIV-positive person to an HIV-negative person.”

But researchers and physicians know very little yet about how treatments for HIV, the virus itself, and the comorbidities associated with HIV affect fertility. So, Kushnir and his colleague, Emory pathologist William Lewis, MD, decided it was time to explore existing data on how HIV and its treatment affect fertility, especially in women. Their review paper on the subject appears in the August 2011 issue of Fertility and Sterility.

Because there are safety concerns and legal restrictions on fertility treatments in couples in which one partner is HIV positive and the other is not, treatment options often are limited.

“This is becoming more and more of an issue,” says Kushnir. “It’s probably time for us to have a more open discussion about the access these patients have to fertility treatment. I think the current system probably discourages these patients from pursuing treatments that are a lot safer than trying to get pregnant on their own.”

Posted on by Robin Tricoles in Immunology Leave a comment

HIV vaccine design: always a moving target

HIV presents a challenge to vaccine design because it is always changing. If doctors vaccinate people against one variety of virus, will the antibodies they produce stop the virus that they later encounter?

A recently published report on an experimental HIV vaccine’s limited effectiveness in human volunteers illustrates this ongoing puzzle in the HIV vaccine field.

Paul Spearman, now chief research officer for Children’s Healthcare of Atlanta and vice chair for research for Emory’s Department of Pediatrics, began overseeing the study when he was at Vanderbilt. The report is in the April 15 issue of the Journal of Infectious Diseases.

Paul Spearman, MD

The vaccine was designed to elicit both antibody and T cell responses against HIV and in particular, to generate broadly neutralizing antibodies. Unfortunately, it didn’t work. Volunteers who received the vaccine made antibodies that could neutralize the virus in the vaccine, but not related viruses thought to be like what participants in a larger study might encounter.

“High levels of neutralizing antibodies can be raised against HIV, while at the same time, breadth of neutralization has never yet been achieved in a vaccine,” Spearman says. “The essential problem is that the antibodies raised have a narrow specificity, while the virus is extremely variable. In contrast, about 20% of HIV-infected individuals will demonstrate neutralization breadth.”

Last year, scientists demonstrated a method for identifying these broadly neutralizing antibodies in HIV-infected individuals. However, having a vaccine hit that target reliably is still elusive.

Spearman reports that he is in charge of a new trial that will be boosting the same individuals that participated in the previous trial with HIV protein from a clade C virus, starting later this year. Clade C is the predominant HIV subtype in southern Africa, while clade B, used in the published trial, is the predominant subtype in North America and Western Europe.

Posted on by Quinn Eastman in Immunology Leave a comment

One reason why SIV-infected sooty mangabeys can avoid AIDS

Sooty mangabeys are a variety of Old World monkey that can be infected by HIV’s cousin SIV, but do not get AIDS. Emory immunologist and Georgia Research Alliance Eminent Scholar Guido Silvestri, MD, has been a strong advocate for examining non-human primates such as the sooty mangabey, which manage to handle SIV infection without crippling their immune systems. Silvestri is division chief of microbiology and immunology at Yerkes National Primate Research Center.

Research shows sooty mangabeys have T cells that can do the same job as those targeted by SIV, even if they don't have the same molecules on their surfaces

A recent paper in the Journal of Clinical Investigation reveals that sooty mangabeys have T cells that perform the same functions as those targeted by SIV and HIV, but have different clothing.

Silvestri and James Else, the animal resources division chief at Yerkes, are co-authors on the paper, while Donald Sodora at Seattle Biomedical Research Institute is senior author.

One main target for SIV and HIV is the group of T cells with the molecule CD4 on their surfaces. These are the “helper” T cells that keep the immune system humming. Doctors treating people with HIV infections tend to keep an eye on their CD4 T cell counts.

In the paper, the scientists show that sooty mangabeys infected with SIV lose their CD4 T cells, without losing the ability to regulate their immune systems. What’s remarkable here is that sooty mangabeys appear to have “double negative” or DN T cells that can perform the same functions as those lost to SIV infection, even though they don’t have CD4.

CD4 isn’t just decoration for T cells. It’s a part of how they recognize bits of host or pathogen protein in the context of MHC class II (the molecule that “presents” the bits on the outside of target cells). Somehow, the T cells in sooty mangabeys have a way to get around this requirement and still regulate the immune system competently. How they do this is the topic of ongoing research.

The authors write:

It will be important to assess DN T cells in HIV-infected patients, particularly to determine whether these cells are preserved and functional in long-term nonprogressors. These efforts may lead to future immune therapies or vaccine modalities designed to modulate DN T cell function. Indeed, the main lesson we have learned to date from this cohort of SIV-infected CD4-low mangabeys may be that managing immune activation and bolstering the function of nontarget T cells through better vaccines and therapeutics has the potential to contribute to preserved immune function and a nonprogressive outcome in HIV infection even when CD4+ T cell levels become low.

Posted on by Quinn Eastman in Immunology Leave a comment

Study Finds Injection Drug Users Who Live Nearer to Syringe Exchange Programs Are Less Likely to Engage in HIV Risk Behaviors

Hannah Cooper

Hannah Cooper, ScD

Injecting drugs is one of the main ways people become infected with HIV in the United States. It is also the main way of becoming infected with the hepatitis C virus (HCV). Injection drug users (IDUs) become infected and transmit the viruses to others through sharing contaminated syringes and through high-risk sexual behaviors. Now a new study published in the American Journal of Public Health offers evidence that proximity to legal syringe exchange programs and pharmacies selling over the counter syringe plays a role in reducing the risk of HIV and Hepatitis C transmission in the U.S.

In a longitudinal study, Hannah Cooper, ScD assistant professor in the Department of Behavioral Sciences and Health Education at Emory University’s Rollins School of Public Health and colleagues studied the behaviors of more than 4000 drug injectors from across 42 New York City health districts beginning in 1995 to 2006. The scientists set out to determine if the relationship of spatial access to syringe exchange programs and pharmacies selling over-the-counter syringes affected the likelihood that local injectors engaged in less HIV risk behaviors.

“It is a well-established fact that syringe exchange programs reduce HIV and related risk behaviors among injection drug users. Here, what we find is that proximity to a syringe exchange program is a powerful determinant of whether injectors inject with sterile syringes,” says Cooper.

The CDC estimates an individual injection drug user injects as many as 1,000 times a year. This adds up to millions of injections across the country each year, creating an enormous need for reliable sources of sterile syringes. Syringe exchange programs provide a way for those IDUs who continue to inject, to safely dispose of used syringes and to obtain sterile syringes at no cost. Many U.S. cities have just one or two syringe exchange programs, but Cooper and her team found IDUs with access to these services in their local neighborhoods were more likely to inject with sterile syringes.

“Our findings suggest that having a syringe exchange program in your neighborhood matters. We need to dramatically scale up the number of syringe exchange programs operating in U.S. cities to increase the number of injectors who live near such a program,” says Cooper.

Posted on by Wendy Darling in Uncategorized 1 Comment

HIV in metro Atlanta concentrated in four-county geographic cluster

The HIV epidemic in metropolitan Atlanta is concentrated mainly in one cluster of four metro area counties – Fulton, DeKalb, Clayton, and Gwinnett that includes 60 percent of Georgia’s HIV cases, according to a study by researchers in the Emory Center for AIDS Research (CFAR).

In a paper published in the Journal of Urban Health, the researchers found that the rate of HIV in the cluster is 1.34 percent. This fits the World Health Organization’s description of a “generalized epidemic” (>1 percent). Outside the cluster, the HIV prevalence in Georgia is 0.32 percent.

The researchers matched HIV prevalence data from the Georgia Division of Public Health, as of October 2007, to census tracts. They also used data from the 2000 census to examine population characteristics such as poverty, race/ethnicity, and drug use.

The large Atlanta HIV cluster is characterized by a high prevalence of poverty along with behaviors that increase the risk of HIV exposure such as injection drug use and men having sex with men.

The investigators also found that 42 percent of HIV service providers in Atlanta are located in the concentrated cluster, which should facilitate prevention and treatment.

Paula Frew, MPH, PhD

“A major aim of our study was to improve public health practice by informing local planning efforts for HIV services,” says corresponding author Paula Frew, MPH, PhD, assistant professor of medicine at Emory University School of Medicine and an investigator in the Emory CFAR.

With more than 50,000 new HIV infections reported yearly in the United States, according to the Centers for Disease Control and Prevention, the HIV/AIDS epidemic continues to be a major public health problem. The number of HIV/AIDS cases is increasing faster in the South compared to other areas of the country. According to Kaiser State Health Facts, Georgia ranks 9th in the nation in the number of HIV/AIDS cases with more than 3,000 new HIV infections diagnosed in 2007.

The study showed differences between Atlanta and other large cities in the distribution of HIV cases. While cases in several other large cities were concentrated in specific neighborhoods, HIV cases in metro Atlanta are more generalized within the four-county metro area. All the cities, however, were similar in the link between HIV, poverty and men having sex with men.

“Prevention efforts targeted to the populations living in this identified area, including efforts to address their specific needs, may be most beneficial in curtailing the epidemic within this cluster,” Frew says.

Other authors of the paper include Emory CFAR members Brooke Hixson, MPH; Saad B. Omer, MBBS, MPH, PhD; and Carlos del Rio, MD.

Posted on by Holly Korschun in Uncategorized Leave a comment

Another avenue of HIV trickery reveals opportunity

Emory and University of Rochester researchers have discovered an extra way by which HIV adapts to survive in a hiding spot in the human immune system. The results are published in the Journal of Biological Chemistry.

A team led by Baek Kim from the University of Rochester and Raymond Schinazi from Emory found that when HIV faces a shortage of the building blocks it usually uses to replicate, the virus adapts by using different building blocks. The discovery may offer scientists a new way to try to stop the virus.

One of HIV’s favorite hiding spots is an immune cell called a macrophage, whose job is to chew up and destroy foreign invaders and cellular debris. One can think of macrophages as worker bees: they don’t reproduce because they’re focused on getting stuff done.

Raymond Schinazi, PhD, DSc, is director of the Laboratory of Biochemical Pharmacology at Emory's Center for AIDS Research

Normally, HIV uses “dNTPs” (building blocks of DNA), but dNTPs are found at very low levels in macrophages because they’ve stopped dividing and making new DNA. Current drugs generally target dNTPs, and aim at the infection in a different type of cells: T cells.

Macrophages do have high levels of RNA building blocks (“rNTPs”). The team found that HIV uses primarily rNTPs instead of dNTPs to replicate inside macrophages. When the team blocked the ability of the virus to interact with rNTPs, its ability to replicate in macrophages was cut by more than 90 percent.

“The first cells that HIV infects in the genital tract are non-dividing target cell types such as macrophages,” Kim says. “Current drugs were developed to be effective only when the infection has already moved beyond these cells. Perhaps we can use this information to help create a microbicide to stop the virus or limit its activity much earlier.”

Compounds that interfere with the use of rNTPs already exist and have been tested as anti-cancer drugs.

“We are now developing new anti-HIV drugs jointly based on this novel approach that are essentially non-toxic and can be used to treat and prevent HIV infections,” Schinazi says.

Baek Kim, PhD

The first authors of the paper are graduate students Edward Kennedy from Rochester and Christina Gavegnano from Emory. Other authors include graduate students Laura Nguyen, Rebecca Slate and Amanda Lucas from Rochester, and postdoc Emilie Fromentin from Emory.

The research was funded by the National Institute of Allergy and Infectious Disease and the Department of Veterans Affairs.

University of Rochester press release

Posted on by Quinn Eastman in Immunology 1 Comment

National AIDS Strategy: Comments on a coordinated effort

In this month’s issue of the journal Future Microbiology, Emory infectious disease physician/scientists Rana Chakraborty and Wendy Armstrong from Emory School of Medicine summarize and comment on the goals and challenges of the National HIV/AIDS Strategy released July 10, 2010.

The National AIDS Strategy was the result of a directive by the Obama Administration to the Office of National AIDS Policy. The strategy’s overall goals were to reduce the number of people who become infected with HIV, to increase access to care and improve health outcomes for people living with HIV, and to reduce HIV-related health disparities.

“The National HIV/AIDS Strategy calls for a long overdue national coordinated effort to curb the rise in new HIV infections and enhance therapy in those already infected,” write the authors.

While the goals are worthy, the strategy will present many challenges, and the authors address each goal individually, and highlight challenges:

  • The initiatives are expensive, and already resources in the United States are not adequate to treat all patients currently diagnosed with HIV infection.
  • Convincing the general population that HIV is still a major problem and an incurable and often-fatal disease will remain a challenge.
  • Nontraditional testing sites outside clinics or hospitals, such as churches, while central to enhancing testing, may present problems of confidentiality.
  • Increasing the number and diversity of available providers of care is difficult given the current financial realities of the American healthcare system where medical practices with a high percentage of HIV patients often can’t break even financially.

The creation of a strategy is a positive step, say the authors, but it needs a clear financial commitment. The strategy’s strengths include a focus on specific high-risk populations, the concept of re-introducing conventional prevention methods including condom distribution and needle-exchange programs, and creating better outreach between leading HIV/AIDS centers in cities and HIV providers in rural settings.

Posted on by Holly Korschun in Uncategorized Leave a comment

Secrets of the elite: Effective immune control of HIV

A small minority of individuals infected with HIV — about one in 300 – are naturally able to suppress viral replication with their immune systems, and can keep HIV levels extremely low for years. Doctors have named these individuals “elite controllers.”

“These individuals have naturally achieved the outcome sought by HIV vaccine researchers worldwide.  Studying them will ultimately inform the design of a more effective HIV vaccine,” says Vincent Marconi, a physician-scientist at Grady Health System’s Infectious Disease Clinic on Ponce de Leon and an associate professor in the Emory School of Medicine.

Vincent Marconi, MD

Marconi is a co-author (along with investigators at over 200 institutions) on a genomics study of elite controllers published Thursday in Science Express. Led by Bruce Walker at Massachusetts General Hospital and Paul de Bakker at the Broad Institute and Brigham and Women’s Hospital in Boston, the team of researchers scanned through the genomes of close to 1,000 elite controllers and 2,600 people with progressive HIV infection. They identified several sites linked with immune control of HIV, all in a region encoding HLA proteins.

HLA proteins play key roles in activating T cell immunity, and are also necessary for the development of T cells. They grab onto segments of proteins, called peptides, inside the cell and carry them to the cell membrane. In the right context, certain viral peptides can mark infected cells for destruction by “killer” T cells.

Previously, MGH/MIT researchers theorized that people with certain forms of their HLA genes develop T cells with a restricted repertoire, yet broader activity. Their T cells would be more likely to still recognize HIV when the virus mutates. A drawback is that these individuals may have a higher risk for developing autoimmune diseases. The theory is described in more detail in this Nature News article.

Marconi is continuing his part of this research into what makes elite controllers’ immune systems special, which he began at the Department of Defense Infectious Disease Clinical Research Program, in collaboration with Eric Hunter, co-director of Emory’s Center for AIDS Research, and research associate Ling Yue at Emory Vaccine Center. The research is supported by the Center for AIDS Research and the National Institute of Allergy and Infectious Diseases.

Posted on by Quinn Eastman in Immunology Leave a comment

Adjuvants: once immunologists’ “dirty little secret”

Two presentations on Emory research at last week’s AIDS Vaccine 2010 conference concerned adjuvants. These are substances that act as amplifiers, stimulating the immune system while keeping its focus on the specific components of a vaccine.

Charlie Janeway (1943-2003)

Immunologist Charlie Janeway once described adjuvants as immunology’s “dirty little secret,” because for a long time scientists did not know how they worked. Some adjuvants can sound irritating and nasty, such as alum and oil emulsion. Alum is the only vaccine adjuvant now licensed for human clinical use in the US. Over the last few years, scientists have learned that adjuvants rev up what is now known as the “innate immune system,” so that the body knows that the vaccine is something foreign and dangerous.

Rama Rao Amara, a vaccine researcher at Emory Vaccine Center and Yerkes National Primate Research Center, and Harriet Robinson, former head of microbiology and immunology at Yerkes and now chief scientific officer at the firm GeoVax, both described extra ingredients for the DNA/MVA vaccine that Robinson designed while at Yerkes in collaboration with NIH researchers.

Read more

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