TAG: "AIDS/HIV"

Scientists ID potential drug to block AIDS


Gladstone plans to launch Phase 2 trial with existing anti-inflammatory.

Warner Greene

Warner Greene

Research led by scientists at the UC San Francisco-affiliated Gladstone Institutes has identified the precise chain of molecular events in the human body that drives the death of most of the immune system’s CD4 T cells as an HIV infection leads to AIDS. Further, they have identified an existing anti-inflammatory drug that in laboratory tests blocks the death of these cells — and now are planning a Phase 2 clinical trial to determine if this drug or a similar drug can prevent HIV-infected people from developing AIDS and related conditions.

Two separate journal articles, published simultaneously today (Dec. 18) in Nature and Science, detail the research from the laboratory of Warner C. Greene, M.D., Ph.D., who directs virology and immunology research at Gladstone, an independent biomedical-research nonprofit. His lab’s Science paper reveals how, during an HIV infection, a protein known as IFI16 senses fragments of HIV DNA in abortively infected immune cells. This triggers the activation of the human enzyme caspase-1 and leads to pyroptosis, a fiery and highly inflammatory form of cell death. As revealed in the Nature paper, this repetitive cycle of abortive infection, cell death, inflammation and recruitment of additional CD4 T cells to the infection “hot zone” ultimately destroys the immune system and causes AIDS. The Nature paper further describes laboratory tests in which an existing anti-inflammatory inhibits caspase-1, thereby preventing pyroptosis and breaking the cycle of cell death and inflammation.

“Gladstone has made two important discoveries, first by showing how the body’s own immune response to HIV causes CD4 T cell death via a pathway triggering inflammation, and secondly by identifying the host DNA sensor that detects the viral DNA and triggers this death response,” said Robert F. Siliciano, M.D., Ph.D., a professor of medicine at Johns Hopkins University and a Howard Hughes Medical Institute investigator. “This one-two punch of discoveries underscores the critical value of basic science — by uncovering the major cause of CD4 T cell depletion in AIDS, Dr. Greene’s lab has been able to identify a potential new therapy for blocking the disease’s progression and improving on current antiretroviral medications.”

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Sustainable science to promote health in Africa


UCSF establishes regional headquarters in East Africa to anchor research, train local scientists.

When someone is diagnosed with HIV in western Kenya, chances are he will get help from FACES, a network of clinics that takes a family-focused approach to prevention, care and treatment of the virus.

Likewise, a villager in Uganda who wants to know her HIV status is likely to get tested at a traveling clinic from SEARCH, a community-based trial with the goal of stopping the spread of HIV through a strategy known as “test and treat.”

Both projects were launched in collaboration with African scientists by researchers from UC San Francisco, which has been working in East Africa for more than two decades. UCSF scientists and clinicians have provided AIDS, tuberculosis and malaria-related treatment to tens of thousands of people, researched the causes and trajectories of the diseases and trained scientists and physicians throughout the region.\

Now, UCSF’s many and varied efforts – which are spread throughout the African continent, but are most concentrated in Uganda, Kenya and Tanzania – finally have a regional headquarters in Nairobi, Kenya, sponsored by the UCSF/Gladstone Center for AIDS Research (CFAR). CFAR also is supporting the expansion of a core immunology lab at the Infectious Diseases Institute (IDI) at Makerere University College of Health Sciences in Kampala, Uganda.

“This will increase the opportunity for UCSF researchers to get involved in collaborative programs in East Africa,” said Phil Rosenthal, M.D., a professor in the Division of Infectious Diseases at San Francisco General Hospital and Trauma Center (SFGH) and a malaria expert who has been training scientists in Uganda for more than a dozen years.

Like others at UCSF, Rosenthal has approached his scientific work with a dual aim: treat disease while sustainably building up the local health care system. These researchers have been at the forefront of a push toward more sustainable work that was embraced as national policy under the leadership of Ambassador Eric Goosby, M.D., who recently returned to UCSF after serving as Obama’s global AIDS coordinator and head of PEPFAR, the President’s Emergency Plan for AIDS Relief.

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HIV plus HPV leads to increased anal cancer risk in men


Researchers also report that smoking increases risk of infection with specific types of HPV.

Dorothy Wiley, UCLA

Dorothy Wiley, UCLA

Human papillomavirus, or HPV, which can cause cervical cancer in women, is also known to cause anal cancer in both women and men. Now, a study led by researchers at the UCLA School of Nursing has found that older HIV-positive men who have sex with men are at higher risk of becoming infected with the HPVs that most often cause anal cancer.

The researchers also report that smoking increases the risk of infection with specific types of HPV among both HIV-infected and uninfected older men by up to 20 percent. This is the first large U.S. study of a group of HIV-infected and uninfected men between the ages of 40 and 69 who have sex with men. Study participants were examined twice a year for up to 25 years.

“Invasive anal cancer is a health crisis for gay, bisexual and other men who have sex with men,” said Dorothy J. Wiley, associate professor at the UCLA School of Nursing and lead author of the study, which was published Nov. 20 in the journal PLOS ONE. “Right now, invasive anal cancer rates among HIV-infected men who have sex with men surpass rates for seven of the top 10 cancers in men.”

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Taming the global AIDS epidemic


Eric Goosby returns to UCSF intent on applying lessons learned as global AIDS ambassador.

Eric Goosby

Eric Goosby

When Eric Goosby, M.D., arrived in Washington, D.C., to lead the Obama administration’s global effort on AIDS in 2009, the world economy was in free fall. Foreign aid budgets were contracting, and many feared the President’s Emergency Plan for AIDS Relief (PEPFAR), begun by President George W. Bush in 2003, might lose the fight against a disease that had already wiped out a generation in Africa.

Four years later, despite funding cuts, the number of HIV-positive people that PEPFAR has put on life-saving antiretroviral therapy has grown fivefold – to 6.5 million. Since treatment stops transmission of HIV, many now speak hopefully about containing the spread of AIDS.

This month, Goosby returns to UC San Francisco, where he earned his medical degree and completed his residency. He’s intent on applying the lessons he learned as head of the largest public health endeavor in history – with $48 billion invested over 10 years – as resources began to shrink.

At UCSF’s Global Health Sciences, Goosby will lead a new center on implementation sciences, a hot, new field in public health and an emerging specialty at UCSF. It examines the practicalities of running public health programs, applying business-world efficiencies to improve them.

Goosby also will return to Ward 86, the AIDS unit at San Francisco General Hospital and Trauma Center where he worked in the early days of the epidemic, when everyone died for lack of effective treatment.

“We are thrilled that Eric is coming back to UCSF and joining Global Health Sciences,” said Jaime Sepulveda, executive director of UCSF Global Health Sciences. “Eric’s experience at the highest levels of international and domestic HIV/AIDS policy and implementation, and his early career as a doctor on the AIDS ward at UCSF, give him unique insights on what works, from both a local and global perspective.”

Read a Q&A, where Goosby discusses the challenges he faced as U.S. Global AIDS Ambassador and what lies ahead in a world where 35 million people – nearly the population of California – are infected with HIV.

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Collaborators in nursing, public health tackle AIDS in China


Part of international effort to limit spread of disease, improve care of those already infected.

Ann Williams (left) and Roger Detels began to collaborate on AIDS research and treatment in China 15 years ago — around the same time that World AIDS Day, every year on Dec. 1, was established to unite people around the globe in the fight against HIV.

Ann Williams (left) and Roger Detels began to collaborate on AIDS research and treatment in China 15 years ago — around the same time that World AIDS Day, every year on Dec. 1, was established to unite people around the globe in the fight against HIV.

Ann Williams, associate dean for research at the UCLA School of Nursing, has traveled the world for nearly 30 years caring for people with HIV/AIDS and conducting research to improve treatment outcomes. Over that same period, Dr. Roger Detels, professor and chair of epidemiology at the UCLA Fielding School of Public Health has taken a similar route, conducting AIDS research and training epidemiologists.

Fifteen years ago, their paths intersected in China, when Detels was looking to include nursing as part of a training program in HIV research for Chinese health care professionals. A professor, Williams signed on, and they have been collaborating ever since as part of an international effort to limit the spread of HIV-AIDS and improve the care of those already infected.

Recently, each received HIV research training grants from the Fogerty International Center at the National Institutes of Health to help scientists and clinicians in developing countries build much-needed research infrastructure.

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UCSF scientist wins $89M grant to study anal cancer


Study will focus on HIV-infected people.

Joel Palefsky, UC San Francisco

Joel Palefsky, UC San Francisco

A UC San Francisco investigator has won an eight-year grant from the National Cancer Institute for a major investigation into anal cancer, a debilitating and sometimes fatal disease largely concentrated among people with HIV.

The total amount of the award over the life of the grant is projected to be approximately $89 million.

Anal cancer disproportionately affects HIV-infected men and women, but the rate of infection is rising among people who do not have HIV and without active intervention, and the number of cases is expected to continue to grow in the general population.

Like cervical cancer and some oral cancers, most cases of anal cancer are associated with human papillomavirus (HPV). Vaccination has been shown to reduce the risk, but the majority of HIV-infected individuals currently at risk for anal cancer are older than age 26, do not qualify for vaccination, and may already have been exposed to the form of HPV known to cause anal cancer.

“Given these strong biological similarities, it is very possible that biomarkers and treatments identified in the study will be applicable to cervical and HPV-associated oral cancer as well,” said Joel Palefsky, M.D., a UCSF professor of medicine and principal investigator of the anal cancer project.

The study will focus on determining the effectiveness of treating anal high-grade squamous intraepithelial lesions (HSIL), which are caused by chronic HPV infection, in reducing the incidence of anal cancer in HIV-infected men and women.

Combined with the possibility that anal cancer is preventable, the incidence of anal cancer is unacceptably high and calls for urgent intervention, Palefsky said.

“Compared with the general population, the incidence of anal cancer is increased more than 100-fold among some risk groups of HIV-infected persons, including many who are successfully treated with combination antiretroviral therapy,” Palefsky said. “There is evidence that anal HSIL is the precursor to invasive anal cancer, which makes it a great target for prevention.”

Palefsky is founder and president of the International Anal Neoplasia Society, which will hold its inaugural annual meeting Nov. 22- 24 in San Francisco.

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UCLA gets $7M to study links between substance abuse, HIV


Study will focus on minority men who have sex with men.

Pamina Gorbach, UCLA

Pamina Gorbach, UCLA

The National Institute on Drug Abuse has awarded UCLA a $7 million grant to investigate the links between substance abuse and HIV among Latino and African-American men who have sex with men.

Researchers will examine how non-injected drugs and alcohol can directly interact with the virus and other infectious diseases, to damage these men’s health. Enrollment in the study begins in January.

Called MASCULINE (MSM and Substances Cohort at UCLA Linking Infections Noting Effects), the study will be led by Pamina Gorbach, a professor of epidemiology at UCLA’s Fielding School of Public Health and a professor of infectious diseases at the David Geffen School of Medicine at UCLA, and Steven Shoptaw, a professor of family medicine at the Geffen School and director of the UCLA Center for Behavioral and Addiction Medicine.

For the study, researchers will establish and maintain an extensive repository of tissue, blood and fluid samples. This repository will be headed by Dr. Peter Anton, a professor of digestive diseases at the Geffen School. Anton, Gorbach and Shoptaw are also members of the UCLA AIDS Institute.

“Alcohol, non-injection use of cocaine and methamphetamine are linked to HIV sexual risk behaviors and transmission of infectious disease,” Gorbach said. “But little is known about how these substances can affect biology to produce health threats among those living with or at risk for HIV — especially among minority men who have sex with men.”

MASCULINE will be a companion study to the Multisite AIDS Cohort Study, the first and largest study specifically created to examine the natural history of AIDS. It will be conducted through the Fielding School’s Behavioral Epidemiology Research Group.

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Cocaine use can make otherwise resistant immune cells susceptible to HIV


UCLA study shows how drugs can impact the body’s defenses against the virus.

UCLA researchers have found that cocaine can make once-resistant immune cells susceptible to infection with HIV.

UCLA researchers have found that cocaine can make once-resistant immune cells susceptible to infection with HIV.

In many ways, the spread of HIV has been fueled by substance abuse. Shared needles and drug users’ high-risk sexual behaviors are just some of the ways that narcotics such as cocaine have played a key role in the AIDS epidemic in much of the world.

There is, however, relatively little research into how drugs can impact the body’s defenses against the virus. But a new UCLA study published in the October issue of the Journal of Leukocyte Biology examines how cocaine affects a unique population of immune cells called quiescent CD4 T cells, which are resistant to the virus that causes AIDS.

The results: Cocaine makes the cells susceptible to infection with HIV, causing both significant infection and new production of the virus.

“The surprising result was that the changes cocaine induced on these cells were very minimal, yet they were sufficient to fuel infection,” said the study’s senior author, Dimitrios Vatakis, an assistant professor of medicine in the division of hematology–oncology at the David Geffen School of Medicine at UCLA. “We found that cocaine mediates its effects directly, inducing minimal changes in the physiology of these cells and utilizing the same pathways it uses to target the brain.”

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Putting the spotlight on global health


UC Irvine professor Brandon Brown is spreading the word about global health.

UC Irvine professor Brandon Brown (right)

UC Irvine professor Brandon Brown (right)

By Katherine Tam

Every few months, UC Irvine professor Brandon Brown returns to Epicentro Salud, a gay men’s community-based clinic in Lima, Peru, to help the staff brainstorm ways to encourage local men to get tested for HIV.

The stigma around homosexuality often deters the gay community from proactively getting tested in Lima, but Brown and clinic leaders have been working to change that these last three years. With Brown’s help, the clinic landed a USAID grant in October 2011 that provided funds to train HIV counselors and bought vital clinic and laboratory equipment.

“Epicentro staff did a lot of outreach to get started. We recruited on Facebook, on the streets, at bars, and were active in the gay pride parade,” Brown said. “We’re seeing more people visiting the center than ever. It’s a big asset for gay men and transgendered individuals in Peru.”

Whether it’s battling HIV stigma in Peru, finding new tools to diagnose malaria in Thailand, or improving sanitation in Kenya, Brown has made it his mission to spotlight the importance of global health and spread the word about the myriad opportunities here and around the globe that people can make a difference.

“Global health is an exciting field and there are lots of ways to get involved,” said Brown, who teaches global health, public health ethics, honors research, and epidemiology. “It’s easy for people to be comfortable in the bubble they’re in. But even if you’re studying say math, you can still be educated on things outside your area of expertise.”

That’s why two years ago, Brown launched a new initiative to put global health on more people’s radar at UC Irvine.

The initiative, Global Health Research Education and Translation (GHREAT),brings together researchers to collaborate on projects, and encourages students to get involved in global health. GHREAT offers courses students can take to earn a global health certificate. In addition, it also offers a global health mentorship program, seminar series and global health job opportunities.

Brown leads GHREAT on his own time and does not receive a salary for it. Neither do the motivated students and faculty who collaborate with him.

So far, students who have participated in GHREAT have become involved in a variety of projects here and abroad: studying how sanitation interventions can prevent contamination of the water supply in Kenya; investigating mental health issues of Iraqi refugees; identifying perceptions of genital warts in Peru; and producing a photo series chronicling the experiences of people living with HIV.

“I don’t think I could have asked for a better mentor,” said Karen Munoz, who graduated in May with a bachelor’s degree in public health and will seek a master’s degree in the same field this fall. “He’s always willing to help, especially when it’s a student’s passion and has to do with global health.”

Munoz credits Brown with her ability to successfully secure a grant from the Undergraduate Research Opportunities Program for her project, which focuses on access to health care among low-income women in Southern California for early detection of the human papillomavirus and cervical cancer.

“When we were applying for grants for our projects, he helped us revise our papers and showed us examples of his so we learned what to do,” Munoz said. “Many of us had never applied for a grant before.”

UC Irvine professor Brandon Brown (center) works closely with the staff at Epicentro in Lima, Peru to help gay men in the community.

UC Irvine professor Brandon Brown (center) works closely with the staff at Epicentro in Lima, Peru, to help gay men in the community.

When he’s not teaching at UC Irvine or spearheading GHREAT, Brown continues to work on global health projects. In addition to weekly Skype calls, he returns to Peru during the year to continue his collaborations with Epicentro.

Jerome Galea, founder of Epicentro, said the grant Brown helped secure early on was instrumental in getting the clinic off the ground.

“Probably if it weren’t for Brandon, Epicentro would not have a clinic today,” Galea wrote via email. “I’ve worked with Brandon for about 10 years and have found myself looking for projects to do with him – even though we’re on different continents – since he’s one of those people that you know you’ll have a great work experience with.”

Brown is working simultaneously on three research projects, including a study on syphilis among gay men in Peru that could lead to better treatment. And he has partnered with a UC San Diego team to research cervical cancer prevention among female sex workers in Tijuana, Mexico.

He hopes more students will take an interest in global health, whether they choose it as their major or not. Eventually, he plans to ask the university to establish an organized research unit in global health, which would provide more funding for projects, synergize global health efforts, help support student travel, and make researchers less dependent on grants.

“Few know what’s possible in global health and how to get involved,” Brown said. “Making more people aware could mean a big difference for all of us globally.”

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Combo of social media, behavior psychology leads to HIV testing


Technique developed at UCLA may apply to other diseases, prevention efforts.

Sean Young, UCLA

Sean Young, UCLA

Can social media be used to create sustainable changes in health behavior?

A UCLA study published Sept. 3 in the peer-reviewed journal Annals of Internal Medicine demonstrates that an approach that combines behavioral science with social media and online communities can lead to improved health behaviors among men at risk of HIV infection.

The evidence-based approach not only led to increased HIV testing and encouraged significant behavioral change among high-risk groups but also proved to be one of the best HIV-prevention and testing approaches on the Internet, according to the study’s lead investigator, Sean D. Young, an assistant professor of family medicine and director of innovation at the Center for Behavior and Addiction Medicine at the David Geffen School of Medicine at UCLA.

And it’s not only applicable to HIV prevention efforts, he noted.

“We found similar effects for general health and well-being,” said Young, who is also a member of the UCLA AIDS Institute. “Because our approach combines behavioral psychology with social technologies, these methods might be used to change health behaviors across a variety of diseases.”

In an earlier study, published in February and also led by Young, researchers found that social media could be useful in HIV- and STD-prevention efforts by increasing conversations about HIV prevention.

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UC awarded $21M in stem cell grants


Diseases targeted include prostate cancer, autism, ALS and AIDS/HIV.

Alysson Muotri, UC San DIego

Alysson Muotri, UC San DIego

The University of California and its affiliates received seven grants totaling more than $21 million in the latest round of funding from the state’s stem cell agency.

Prostate cancer, autism, ALS and AIDS/HIV are among the diseases targeted by the California Institute for Regenerative Medicine, whose governing board awarded a total of more than $40 million in funding for this round.

Overall, CIRM’s governing board has awarded more than $1.8 billion in stem cell grants, with half of the total going to the University of California or UC-affiliated institutions.

CIRM Early Translation Awards IV:

  • UC Irvine: $4.3 million: Magdalene Seiler
  • UCLA: $13 million: Donald Kohn, Gerald Lipshutz, Robert Reiter, Jerome Zack
  • UC San Diego: $1.8 million: Alysson Muotri
  • UCSF-affiliated J. David Gladstone Institutes: $2.3 million: Steven Finkbeiner

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New intervention reduces risky sex among bisexual African-American men


Holistic approach takes into account cultural considerations.

Nina Harawa, UCLA

Nina Harawa, UCLA

A culturally tailored HIV prevention program developed and tested by investigators at UCLA and the Charles R. Drew University of Medicine and Science has been shown to significantly reduce unprotected sex among bisexual black men.

The innovative approach, called Men of African American Legacy Empowering Self, or MAALES, is described in an article in the peer-reviewed journal AIDS.

The rate of HIV/AIDS among African-Americans is significantly higher than it is among any other ethnic or racial group. (According to the Centers for Disease Control and Prevention, African-Americans accounted for an estimated 44 percent of new U.S. HIV diagnoses in 2010.) Among men who have sex with men, black men account for the largest estimated number of HIV infections. Yet there are few interventions available to reduce those rates, said the study’s principal investigator, Nina Harawa, adjunct assistant professor of epidemiology at UCLA and associate professor of research at the Charles R. Drew University of Science and Medicine.

MAALES takes a holistic approach to minimizing behaviors that could put men at risk for HIV, engaging participants in small-group discussions about popular media, exercises such as negotiating condom use with sexual partners and activities to improve the participants’ knowledge of sexual health. Importantly, the intervention is also culturally relevant, addressing participants’ shared legacies, including social expectations of African-American men, historical discrimination and disenfranchisement, and societal impacts on individual health and sexual decision-making.

“When we first set out in 2004 to develop an intervention for behaviorally bisexual African-American men, the gap between documented need and services was staggering,” Harawa said. “Up to that point, just one prevention intervention tailored for African-American men who had sex with men had been developed and no interventions designed for behaviorally bisexual men of any race or ethnicity had been published.”

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