Research links HIV to age-accelerating cellular changes

Study suggests adults infected with virus can develop age-related diseases before peers.

Beth Jamieson, UCLA

By Enrique Rivero, UCLA

People undergoing treatment for HIV-1 have an increased risk for earlier onset of age-related illnesses such as some cancers, renal and kidney disease, frailty, osteoporosis and neurocognitive disease. But is it because of the virus that causes AIDS or the treatment?

To answer that question, researchers at the UCLA AIDS Institute and Center for AIDS Research and the Multicenter AIDS Cohort Study investigated whether the virus induces age-associated epigenetic changes — that is, changes to the DNA that in turn lead to changes in expression of gene levels without changing the inherited genetic code. These changes affect biological processes and can be brought on by environmental factors or by the aging process itself.

In a study published online in the peer-reviewed journal PLOS ONE, the researchers suggest that HIV itself accelerates these aging related changes by more than 14 years.

“While we were surprised by the number of epigenetic changes that were significantly associated with both aging and HIV-infection, we were most surprised that the data suggests HIV-infection can accelerate aging-related epigenetic changes by 13.7 to 14.7 years,” said Beth Jamieson, professor of medicine in the division of hematology/oncology at the David Geffen School of Medicine at UCLA and one of the study’s senior authors. “This number is in line with both anecdotal and published data suggesting that treated HIV-infected adults can develop the diseases of aging mentioned above, approximately a decade earlier than their uninfected peers.”

The researchers examined samples of white blood cells stored by UCLA’s MACS site, which has been collecting biological samples as well as clinical, behavioral and socioeconomic data on men infected with HIV and men at risk for HIV infection since 1983. The scientists selected white blood cell samples from both young (20 to 35 years old) and older (36 to 56) adults who at the time had not started antiretroviral therapy. They divided each group into 12 HIV-infected and 12 age-matched HIV-uninfected samples for a total of 96 samples, and then extracted the DNA from the samples and analyzed it for epigenetic patterns.

They compared epigenetic patterns that are strongly associated with aging to changes that occur during HIV-infection and found significant overlap in the two patterns, and used those overlapping patterns to estimate the biological age of HIV-infected, untreated adults. The researchers found that at the epigenetic level, the adults appeared to be approximately 14 years older than their chronologic age, said Jamieson, who also is director of the UCLA Flow Cytometry Core.

Although the findings demonstrated that HIV infection can accelerate aging-related epigenetics, the researchers could not determine whether antiretroviral therapy restores those patterns to be more age-appropriate or whether the drugs themselves cause additional changes.

Taken together, however, “these data suggest that HIV-1 infection does accelerate some aspects of aging and that general aging, and HIV-1 related aging, work through at least some common mechanisms,” the authors write. “These results are an important first step for finding potential therapeutic approaches to mitigate the effects of both HIV and aging.

The study’s co-authors are Tammy Rickabaugh, Ruth Baxter, Mary Sehl, Janet Sinsheimer, Patricia Hultin, Lance Hultin, Austin Quach, Otoniel Martinez-Maza, Steve Horvath and Eric Vilain, all of UCLA.

The study was supported by a National Institute on Aging grant (1RO1-AG-030327), a UCLA AIDS Institute/CFAR seed grant from the National Institutes of Health (AI-028697) an NIH T032 training grant (5T32GM008243-25) and a National Science Foundation grant (DMS-1264153).

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For most children with HIV, low immune cell count, cells rebound after treatment

Study led by UCLA doctor finds t-cell level returns to normal with time.

Paul Krogstad, UCLA

By Enrique Rivero, UCLA

Most children with HIV who have low levels of a key immune cell eventually recover levels of this cell after they begin treatment, according to a new study conducted by researchers at UCLA and other institutions in the U.S. and Brazil.

The researchers were funded by the National Institutes of Health.

“We were pleased to find that the vast majority of children experience immune system recovery with effective therapy,” said Dr. Paul Krogstad, professor of pediatric infectious diseases and of molecular and medical pharmacology at the David Geffen School of Medicine at UCLA, and the study’s first author. “Our study also provided the most detailed information to date about the timing of this recovery in school-age children.”

Krogstad is also a member of the UCLA AIDS Institute and Center for AIDS Research.

CD4+ t cells are a major target of HIV. In about 15 percent of adult patients, the cells fail to rebound after the virus has been suppressed with medication, a scenario that is associated with life-threatening illnesses.

The new study, which was published online in the journal AIDS, was intended to determine to what extent children who were infected with HIV around the time of birth were at risk for this condition and whether this failure carried with it a major risk for serious infection.

The failure of CD4+ t cells to rebound occurs only infrequently in young children with HIV, said Rohan Hazra, a study author and the chief of the maternal and pediatric infectious disease branch at the NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development, which provided much of the funding for the study.

“The comparatively few children whose CD4+ cells failed to rebound did not appear to be at any greater risk for serious infection than children with higher CD4+ counts,” he said.

Hazra added that the findings do not appear to change treatment recommendations for children with HIV: antiretroviral treatment to suppress the virus and periodic follow-up examinations to detect the first signs of any serious infections.

To conduct their analysis, researchers reviewed data from three research networks caring for more than 3,700 children in the U.S., Central and South America, and the Caribbean who were infected with HIV before or during birth. The researchers followed the CD4+ cell counts of 933 children who were at least 5 years old when they started anti-HIV treatment. Healthy CD4+ cell counts range from 500 to 1,200 cells per blood sample. Fewer than 500 cells per sample is considered low, and 200 or fewer per sample is considered very low. After one year of anti-HIV treatment, 86 percent of children in the study achieved CD4+ counts of 500 or more. After two years of anti-HIV treatment, 92 percent surpassed this threshold.

The researchers also reviewed the children’s records for signs of serious illness during the course of their treatment. Known as CDC Category C events, these illnesses are a sign of the seriously weakened immune system in people with AIDS. A total of nine children experienced such events. The occurrence of these events did not differ statistically between those having CD4+ cell counts below 500 at the time of the event (four children) and those with counts above 500 (five children).

The study authors noted that compared to adults with low CD4+ counts at the beginning of treatment, CD4+ counts in children increase to 500 or more with time after treatment has begun. Yet, despite such increases, some children had Category C conditions or other significant illnesses during the first three years of HIV treatment. The researchers wrote that additional studies are needed to understand this higher risk of illness.

Additional funding was provided by several NIH institutes: the National Institute on Drug Abuse, the National Institute of Allergy and Infectious Diseases, the Office of AIDS Research, the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, the National Institute on Deafness and Other Communication Disorders, the National Heart Lung and Blood Institute, the National Institute of Dental and Craniofacial Research, and the National Institute on Alcohol Abuse and Alcoholism.

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Building mini-brains to study disorders caused by HIV, meth use

UC San Diego scientist wins $2.5M award to create stem cell-derived models.

By Scott LaFee, UC San Diego

A UC San Diego School of Medicine project involving the creation of miniature models of the human brain – developed with stem cells – to study neurological disorders caused by HIV and methamphetamine use has been named one of five recipients of the 2015 Avant-Garde Award for HIV/AIDS Research from the National Institute on Drug Abuse (NIDA).

The project, headed by Tariq M. Rana, Ph.D., professor of pediatrics, will receive $500,000 per year for five years.

“The human cerebral cortex has evolved strikingly compared to those of other species, and no animal model accurately captures human-specific brain functions,” said Rana. “The creation of mini-brains, or organoids, will permit, for the first time, study of the toxic effects of addiction and HIV on the human brain in a dish. This offers us the exciting opportunity to design patient-specific model systems, which could potentially revolutionize drug discovery and precision medicine for central nervous system disorders.”

The Avant-Garde Awards are granted to scientists who propose high-impact research that could open new avenues for prevention and treatment of HIV/AIDS among drug abusers. The term “avant-garde” is used to describe highly innovative approaches that have the potential to be transformative.

“Despite the success of combined antiretroviral therapies, HIV remains a chronic disease with a host of debilitating side effects that are exacerbated in those suffering from substance use disorders,” said NIDA Director Nora D. Volkow, M.D.  “These scientists have proposed creative approaches that could transform the way we think about HIV/AIDS research, and could lead to the development of exciting new tools and strategies to prevent infections and improve the lives of substance abusers infected with HIV.”

The other 2015 recipients are:

  • Don C. Des Jarlais, Ph.D., Mount Sinai Beth Israel
  • Eli Gilboa, Ph.D., University of Miami School of Medicine
  • Nichole Klatt, Ph.D., University of Washington, Seattle
  • Alan D. Levine, Ph.D., Case Western Reserve University

For more information about the Avant-Garde Award Program and 2015 recipients, visit drugabuse.gov/about-nida.

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Birth control shot linked to moderately increased risk of HIV infection

UC Berkeley findings have potentially broad implications.

By Sarah Yang, UC Berkeley

A large meta-analysis of 12 studies in sub-Saharan Africa found that women who used a type of injectable birth control had a moderately increased risk of becoming infected with HIV.

The contraceptive, depot medroxyprogesterone acetate, is sold under the brand name Depo-Provera, and it is administered as a shot every three months.

The findings, published today in The Lancet Infectious Diseases, included data from 39,500 women. The researchers selected the studies based upon methodological rigor, such as whether they accounted for the use of condoms.

In addition to Depo-Provera, the studies also examined other commonly prescribed forms of hormonal contraception, such as the injectable norethisterone oenanthate (sold as NET-EN), combined oral contraceptives and progestin-only pills. The other birth control methods did not appear to increase HIV infection risk for women in the general population.

“We embarked on this study because of the inconsistency in the scientific literature on this topic,” said study lead author Lauren Ralph, who did this research for her UC Berkeley Ph.D. dissertation in epidemiology. “The results have potentially broad implications because hormonal contraceptives remain popular for women worldwide.”

Approximately 144 million women worldwide use hormonal contraception, and of those about 41 million women use injectable forms of birth control instead of the pill.

The study found that women who used depot medroxyprogesterone acetate had a moderate, 40 percent increased risk of acquiring HIV compared with women using non-hormonal methods and those not practicing birth control. The increased risk was slightly lower, 31 percent, among the studies done in women in the general population.

It remains unclear why the increased risk was seen among those using Depo-Provera but not the other forms of hormonal contraception, the authors said. One possibility may be that birth control with higher levels of progestin, the synthetic form of the natural hormone progesterone, changed the vaginal lining or altered local immunity, increasing the risk for HIV infection, though the researchers emphasized that this study did not examine the physiological effects of the different contraceptive methods and more research on potential underlying biologic mechanisms is needed.

The researchers cautioned that the increased HIV infection risk needs to be considered in the context of the risks associated with not using birth control.

“We do not believe that the findings merit withdrawal of this method of birth control for most women,” said Ralph. “There are significant risks associated with pregnancy and childbirth as well. It can be tricky to ensure a reliable supply of contraceptives in sub-Saharan Africa. Removing Depo-Provera doesn’t mean the women will have immediate access to other methods of birth control that are as effective. Ultimately, decisions around which birth control method to use should be made between a woman and her healthcare provider.”

The researchers noted that the results highlight the need for more studies among high-risk populations.  Among the 12 studies analyzed, only two included sex workers or women with HIV-positive partners.

“The most important next steps for women all over the world are to examine ways to broaden women’s contraceptive options and increase uptake of other safe and effective contraceptive methods, and to step up research on new contraceptive methods, especially those that protect against both HIV and pregnancy,” said senior author Nancy Padian, a UC Berkeley adjunct professor of epidemiology.

Other co-authors of this study are Sandra McCoy, a UC Berkeley assistant adjunct professor of epidemiology, and Karen Shiu, who was a research analyst in Padian’s research group at the time of the study.

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New stem cell technique shows promise in HIV resistance

UC Davis research paves way for human clinical trials using gene therapy.

Joseph Anderson, UC Davis

By Charles Casey, UC Davis

Using modified human stem cells, a team of UC Davis scientists has developed an improved gene therapy strategy that in animal models shows promise as a functional cure for the human immunodeficiency virus (HIV) that causes AIDS.  The achievement, which involves an improved technique to purify populations of HIV-resistant stem cells, opens the door for human clinical trials that were recently approved by the U.S. Food and Drug Administration.

“We have devised a gene therapy strategy to generate an HIV-resistant immune system in patients,” said Joseph Anderson, principal investigator of the study and assistant professor of internal medicine. “We are now poised to evaluate the effectiveness of this therapy in human clinical trials.”

Anderson and his colleagues modified human stem cells with genes that resist HIV infection and then transplanted a near-purified population of these cells into immunodeficient mice. The mice subsequently resisted HIV infection, maintaining signs of a healthy immune system.

The findings are now online in a paper titled “Safety and efficacy of a tCD25 pre-selective combination anti-HIV lentiviral vector in human hematopoietic stem and progenitor cells,” and will be published in the journal Stem Cells.

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A sense for biosensors

UC Irvine’s Weian Zhao has created a device that improves detection of bacterial, viral invaders in blood samples.

The Integrated Comprehensive Droplet Digital Detection system invented by Weian Zhao of UC Irvine converts blood samples directly into billions of very small droplets. (Photo by Steve Zylius, UC Irvine)

By Tom Vasich, UC Irvine

As a doctoral student at McMaster University in Hamilton, Ontario, Weian Zhao took part in a Canada-wide research effort to develop bioactive paper that would detect, capture and deactivate waterborne and airborne pathogens.

As part of this project, he helped invent gold nanoparticle-coated paper that could detect common pathogens, such as E. coli, but ultimately, the product didn’t meet his exacting standards of diagnostic speed and sensitivity. With a freshly minted Ph.D. in chemistry, Zhao moved on to a joint postdoctoral fellowship at both the Massachusetts Institute of Technology and Harvard, where he dove into stem cell research, his biosensor work seemingly left north of the border.

But the challenge of creating a technology that could rapidly and selectively identify bacterial and viral invaders in blood samples nagged at the young scientist, even as he joined UC Irvine in 2011 as an assistant professor of pharmaceutical sciences with state-of-the-art lab space in the Sue & Bill Gross Stem Cell Research Center.

And then he met Enrico Gratton. In his Laboratory for Fluorescence Dynamics, the UCI biomedical engineer and colleagues have been developing imaging tools for biomedical applications. Among them is a three-dimensional particle counter that tags low-concentration fluorescent particles in large volumes of solution within several minutes, which drew Zhao’s attention. He knew he was back in the biosensor game.

Employing this particle counter, Zhao created a bloodstream infection test that speeds up diagnosis times with unprecedented accuracy – allowing physicians to treat patients with potentially deadly ailments more promptly and effectively.

Zhao says that the Integrated Comprehensive Droplet Digital Detection system can, in as little as 90 minutes, detect bacteria in milliliters of blood with single-cell sensitivity; no cell culture is needed. He published his latest results in the November issue of Nature Communications.

“We are extremely excited about this technology because it addresses a long-standing unmet medical need in the field,” says Zhao, who also holds a faculty appointment in biomedical engineering. “As a platform technology, it may have many applications in detecting extremely low-abundance biomarkers in other areas, such as cancers, HIV and, most notably, Ebola.”

Bloodstream infections are a major cause of illness and death. In particular, infections associated with antimicrobial-resistant pathogens are a growing health problem in the U.S. and worldwide. According to the Centers for Disease Control & Prevention, more than 2 million people a year globally get antibiotic-resistant blood infections, with about 23,000 deaths. The high mortality rate for blood infections is due, in part, to the inability to rapidly diagnose and treat patients in the early stages.

Recent molecular diagnosis methods, including polymerase chain reaction, can reduce the assay time to hours but are often not sensitive enough to detect bacteria that occur at low concentrations in blood, as is common in patients with incipient blood infections.

The Integrated Comprehensive Droplet Digital Detection technology differs from other diagnostic techniques in that it converts blood samples directly into billions of very small droplets. Fluorescent DNA sensor solution infused into the droplets detects those with bacterial markers, lighting them up with an intense fluorescent signal. Zhao says that separating the samples into so many small drops minimizes the interference of other components in blood, making it possible to directly identify target bacteria without the purification typically required in conventional assays.

“The IC 3D instrument is designed to read a large volume in each measurement, to speed up diagnosis,” Gratton says. “Importantly, using this technique, we can detect a positive hit from hundreds of millions of measurement samples with very high confidence.”

But invention was only the first step. Zhao wants to commercialize IC 3D. At UCI, faculty researchers with an entrepreneurial bent can work with the Institute for Innovation, an interdisciplinary and campuswide center focused on integrating research, entrepreneurship and technology to create real-world applications that benefit the public and drive the economy. The Office of Technology Alliances, part of the institute, helped Zhao patent-protect the IC 3D technology and establish a spin-off company, Velox Biosystems, to test and manufacture a commercial IC 3D device.

Currently, Zhao is focusing on applying IC 3D to cancer treatments – an extension of the research he’s been advancing since joining UCI.

Zhao has been developing stem cell messengers that selectively migrate to cancer sites to deliver tumor-fighting drugs or probes for contrast-enhanced medical imaging. This could, potentially, enable the identification of cancer micro-metastases at their early stages and increase the effectiveness of chemotherapeutic treatments for metastatic cancer while mitigating the symptoms associated with systemic chemotherapy.

For this work, Zhao was included in the MIT Technology Review’s 2012 list of the world’s top innovators under the age of 35, and this year he earned a prestigious National Institutes of Health Director’s New Innovator Award to further his efforts to create stem cell-based detection methods and treatments for cancer.

He’s also collaborating with Dr. Jason Zell, an assistant professor of medicine and co-leader of the Colon Cancer Disease-Oriented Team at UCI’s Chao Family Comprehensive Cancer Center, to use IC 3D to identify biomarkers in colon cancers. This could enable oncologists to gauge the effectiveness of treatment during the cancer’s early stages more accurately than with current methods, which Zell says are not reliable.

Zhao is now seeking business partners to accelerate Velox Biosystems’ growth and hopes to conduct clinical studies of IC 3D’s utility in patient diagnosis and treatment.

“That’s what’s so important about this project,” he says. “We’ve created a multi-platform tool that has the potential to work with a variety of infections and diseases. I’m very excited about its future.”

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Combining social media, behavioral psychology could lead to more HIV testing

UCLA research suggests a valuable tool in fight against the virus that causes AIDS.

Sean Young, UCLA

By Enrique Rivero, UCLA

Social media such as Twitter and Facebook can be valuable in the fight against HIV in the United States, where research has demonstrated they can prompt high-risk populations to request at-home testing kits for the virus that causes AIDS, suggesting a way to potentially boost testing rates.

But does it lead to actual testing, and can it work outside the United States? A new study from the UCLA AIDS Institute and Center for AIDS Research published online today (Dec. 15) by the peer-reviewed journal Lancet HIV suggests that it can. The study, conducted in Peru among men who have sex with men, found that participants in the intervention arm of a randomized controlled clinical trial were more than twice as likely to be tested for HIV than those who joined a social media group and were provided with traditional HIV prevention services.

The intervention, called Harnessing Online Peer Education (HOPE), combines social media with behavioral psychology to encourage people in high-risk populations to get tested, said Sean Young, assistant professor of family medicine at the David Geffen School of Medicine at UCLA and executive director of the UCLA Center for Digital Behavior.

“This shows that it’s not just social media that got people to test, but the HOPE social media interventions and the psychological ingredients it used for changing behavior,” Young said. “In other words, if you’re a public health organization or worker, don’t just think that throwing something on Facebook or Twitter will solve your problems and change people’s behaviors. Social media may be helpful, but the HOPE intervention was significantly more likely to change HIV testing behavior compared to traditional care through social media.”

Though there have been many experimental HIV testing interventions in international settings, none have used social media technologies, said Young, who is also a member of the UCLA AIDS Institute and Center for AIDS Research, the Center for HIV Identification, Prevention and Treatment Services and the UCLA Center for Addiction and Behavioral Medicine. This study was conducted in greater Lima, which reflects the low- and middle-income countries where low-cost interventions such as HOPE could help stem the spread of AIDS.

Previous research by Young and colleagues demonstrated that the HOPE intervention increased participants’ requests for testing, but was too small to determine the rates of actual testing. “That pilot study was a good enough start showing the potential of using the HOPE intervention to change testing behavior,” he said.

This study builds on the prior research by increasing the number of participants by about five times — 556 participants compared to  112 — and it was designed with a verifiable and observable endpoint allowing the researchers to gauge the rates at which participants followed through with requests for kits and got tested.

The 556 Peruvian men who have sex with men were randomly assigned to join control groups or private intervention on Facebook for 12 weeks, with 278 assigned to each group. The control group received an enhanced standard of care, which included standard offline HIV prevention and testing services offered by local clinics and organizations and participation in Facebook groups that provided study updates and HIV testing information.

The intervention group, by contrast, received the enhanced standard of care and also incorporated the HOPE intervention behavior change model, which utilized peer leaders who sent messages, chats and wall posts and engaged the participants in general friendly conversation. The peer leaders also communicated information about HIV prevention and testing to the participants.

Of the 278 participants in each group, 26 from the intervention group  did not complete the follow-up survey and 32 were lost to follow-up on the control side.  Of the 252 from the intervention group who provided complete data, 43 (17 percent) went on to take an HIV test, compared with 16 (7 percent) of the controls. In the study, seven participants who tested positive were linked to care at a local clinic.

Though this research provides evidence that the HOPE intervention can increase HIV testing in low- and middle-income countries, other settings are different from Peru, so the researchers can’t say for certain if these findings are applicable to other countries.

This study, however, suggests that the HOPE intervention and new technologies can be a low-cost solution for populations at risk for HIV in Peru and other similar low- and middle-income country settings, Young said.

“This could set the stage for important future work on being able to use these methods to treat people who have HIV, which is a tremendous issue in settings like sub-Saharan Africa,” Young added.

Grants from the National Institute of Mental Health (K01 MH090884) and the UCLA AIDS Institute and Center for AIDS Research funded this study.

Study co-authors are William Cumberland, Roch Nianogo, and Thomas Coates of UCLA; Luis Menacho of Universidad Peruana Cayetano Heredia (Peru), and Jerome Galea of Epicentro Gay Men’s Community Center (Lima, Peru).

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Marking World AIDS Day

Physician from UC San Diego’s HIV specialty care clinic gives talk on HIV preventive pill.

UC San Diego hosted a viewing of portions of the AIDS Memorial Quilt as part of World AIDS Day. (Photo by Erik Jepsen, UC San Diego)

By Christine Clark, UC San Diego

UC San Diego recognized World AIDS Day Dec. 1, embracing the “Getting to Zero” theme to convey the global community effort needed to achieve zero new HIV infections, zero stigma against those living with HIV/AIDS and zero AIDS-related deaths.

This is the third year in a row the campus has marked World AIDS Day with the “Getting to Zero” theme. “We have known for years that this theme, in a number of ways, is a must for us to be effective in the fight against HIV,” said Shaun Travers, director of UC San Diego’s LGBT Resource Center and chair of the World AIDS Day planning committee.

The day included a variety of free and public events, including a viewing of portions of the AIDS Memorial Quilt, which is the largest ongoing community arts project in the world. In conjunction with the theme, the day also featured a talk from Dr. Ankita Kadakia, an HIV/AIDS specialist from UC San Diego’s HIV specialty care clinic, the Owen Clinic. Kadakia gave a presentation about the new once-a-day pill to help prevent HIV infections, Pre-Exposure Prophylaxis (PrEP), which may be the most effective way for people who do not have HIV to prevent HIV infection.

UC San Diego has been on the cutting edge of testing the effectiveness of the PrEP pill (brand name Truvada). In 2012, UC San Diego researchers received a $5.6 million grant to test PrEP’s ability to keep high-risk individuals from becoming infected with HIV.

“PrEP is one of the most promising new ways that we can achieve the goal of stomping out HIV/AIDS, and Kadakia’s presentation is a great way the World AIDS Day theme is being brought to life through research right here at UC San Diego,” Travers said. “This will be the generation that stops HIV/AIDS.”

When the first clinical reports of AIDS emerged more than 30 years ago, those diagnosed with the then-mysterious disease faced a looming death sentence. Most had just months to live. Kadakia explained how much has changed since them. “This is a very exciting time to be in this field,” Kadakia said.

Today, scientists and physicians better understand the pathology of HIV/AIDS and the advent of antiretroviral drugs (prescribed in the early stages of infection) can often render HIV/AIDS a chronic but livable condition. Patients can live relatively normal, full lives for decades after diagnosis and now, for the first time, there is a drug to prevent people from getting infected with HIV.

The PrEP pill contains two medicines (tenofovir and emtricitabine) that are used in combination with other medicines to treat HIV. When someone is exposed to HIV through sex or injection drug use, these medicines can work to keep the virus from establishing a permanent infection.

Kadakia explained how multiple studies followed individuals who were considered high risk for contracting HIV. These subjects, who were followed over the course of multiple years, were prescribed with either a placebo or PrEP and all were given strategies on how best to prevent HIV infection.

Those considered high risk, including the subjects in the PrEP studies, are: individuals who have multiple sex partners without using a condom, persons who are using or recently used intravenous drugs, and people living in areas where there are high levels of HIV/AIDS infection in the population.

The studies ultimately revealed that when taken consistently, on a daily basis, PrEP has been shown to reduce the risk of HIV infection in people who are at high risk by up to 92 percent. PrEP is much less effective if it is not taken consistently.

Kadakia emphasized, the most effective way to prevent HIV infection through sexual intercourse (99 percent) is by using a condom.

“I can’t stress enough the importance of using a condom,” Kadakia said. “PrEP is not a miracle pill. It also cannot stop pregnancy, nor can it prevent the transmission of other sexually transmitted diseases.”

Kadakia explained why the PrEP pill has not been widely distributed in the U.S. yet. “Though, the information on PrEP has been available for years, the medical community is not ‘putting it in the water’ because of concerns over people building a resistance mutation if they developed HIV,” she said. “However, those who are considered high risk for contracting the virus should ask their doctor about the PrEP pill.”

Kadakia says she expects the drug to undergo more studies in the coming years.

“Is PrEP the next step we’re taking toward ending HIV? Possibly,” Kadakia said. “Education is going to continue to be a really important tool in this battle. What I tell my patients is ‘protect yourself. Wear a condom. You can’t protect your partner from getting HIV, but you can protect yourself. It’s the safest method.’”

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Related links:
-UC San Diego recognizes World AIDS Day with memorial quilt display and other events
-UCLA: Q&A: David Gere and the fight to end AIDS
-UC San Francisco: Then and now: How nurses shaped care for HIV/AIDS patients

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To stop spread of HIV, African governments should target hot zones

UCLA develops strategy using a complex mathematical model.

By Mark Wheeler, UCLA

While Ebola has attracted much of the world’s attention recently, a severe HIV epidemic rages on around the world and in sub-Saharan Africa in particular. Globally, more than 34 million people are infected with HIV; in sub-Saharan Africa alone, 3 million new infections occur annually.

In an attempt to stop the spread of HIV, governments in the region are considering providing antiretroviral drugs to people who do not have the virus but are at risk for becoming infected. Such drugs are known as pre-exposure prophylaxis, or PrEP.

Although the conventional strategy — attempting to attempt to distribute the drugs to people in every city and village — might seem logical and equitable, researchers at UCLA have devised a plan they say would be much more effective in reducing HIV transmission.

The strategy, developed using a complex mathematical model, focuses on targeting “hot zones,” areas where the risk of HIV infection is much higher than the national average. In South Africa, where 17 percent of the population is infected with HIV, the model predicted that targeting hot zones would prevent 40 percent more HIV infections than using the conventional strategy — and would therefore be 40 percent more cost-effective.

“Stopping the HIV pandemic is one of the greatest challenges facing the global community,” said Sally Blower, the paper’s senior author and the director of the Center for Biomedical Modeling at the UCLA Semel Institute for Neuroscience and Human Behavior.

The report appears in the current online edition of Nature Communications.

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David Gere and the fight to end AIDS

As we commemorate World AIDS Day on Dec. 1, is the end in sight?

Michel Sidibé, executive director of the Joint United Nations Programme on HIV/AIDS, actress Charlize Theron and professor David Gere, head of the UCLA Art and Global Health Center, gathered at Glorya Kaufman Hall for an announcement of a UNAIDS plan to end the AIDS epidemic by 2030. (Photo courtesy of UNAIDS/AFP News Agency)

By Mary Daily and Cynthia Lee, UCLA

Through the UCLA Art and Global Health Center he created, visionary director and professor David Gere of the Department of World Arts and Cultures has used art and a network of artists to communicate his message about ending the AIDS epidemic around the world. On Tuesday, Nov. 18, before World AIDS Day 2014 (Dec. 1), Michel Sidibé, the executive director of the Joint United Nations Programme on HIV/AIDS (UNAIDS), came to Glorya Kaufman Hall to announce a plan to accomplish just that by 2030. South African and American actress Charlize Theron, the founder of an Africa outreach project and a designated UN Messenger of Peace, also talked about the progress that’s being made in Africa. More than 100 people, from UCLA students to longtime researchers associated with the UCLA AIDS Institute, were at the event hosted by Gere and sponsored by the center. The new UNAIDS report, “Fast-Track: ending the AIDS epidemic by 2030,” maintains that nearly 28 million new HIV infections and 21 million AIDS-related deaths would be averted if the 2030 plan succeeds. 

UCLA Newsroom editor Cynthia Lee talked to Gere about the UNAIDS effort while UCLA Magazine editor Mary Daily spoke with him earlier about how he became an AIDS activist through art for a Q&A that ran in the magazine

How would you characterize the UNAIDS plan to end the epidemic? Is it a realistic goal?
I would characterize the 2030 goal as “aspirational,” based on exciting data indicating that early treatment to reduce viral load substantially lowers infection rates. At the announcement, UNAIDS director Michel Sidibé  took out a strip of red paper as a visual aid to explain that global efforts have already managed to bend down the rising arc of the AIDS infection, but that now we need to “break” it so that it doesn’t spring back — a graphic and telling image.

Will the UCLA Art and Global Health Center play a role in bringing this goal to fruition?
Absolutely. The whole purpose of the Art and Global Health Center is to get creative people — artists — sitting at the table with medical and public health professionals. My argument is that artists can do three very important things: communicate life-saving information memorably, influence policymakers to do the right thing and reduce the stigma of HIV so that people will get themselves tested and treated. Early treatment is the key to the UNAIDS strategy.

Why did UNAIDS decide to make this announcement at UCLA?
The significance of that choice was not lost on me. UCLA doctors identified the first cases of a rare immunodeficiency, later called HIV or AIDS, in 1981. Now, in 2014, it’s up to us to commit to watching over the last cases of AIDS.

Let’s look at how your intervention in the AIDS epidemic began. I understand it wasn’t until you got to San Francisco at the height of the epidemic that you began to see art as a way to address a grievance or save lives.

When I arrived in 1985, it seemed that all the new art and performance in the U.S. was a response to the AIDS crisis. Joe Goode’s dances were about his dead friends. Ross Bleckner’s paintings looked like his search for a parallel spirit world. But it wasn’t just the new art. I would go see “Giselle” at the San Francisco Ballet, in which the main character, who had died from heartbreak, comes back as a haunting. I realized that everybody in the audience was thinking that this ballet, made more than 100 years ago, was about us and the hauntings we felt from the loss of our friends. That was when I knew that art could do more than be pretty.

Why was dance particularly well-suited to address HIV and AIDS?
A: In the mid-1980s, there were a lot of gay men in dance and a lot of gay men affected by HIV, though it’s certainly not a gay disease. The HIV retrovirus has no idea of your sexuality, your profession or who you are. But those in the dance world were deeply affected, and it was their chosen profession to use bodies to make their point. The body is where ideas, feelings and activism implode. The AIDS crisis brought out the latent potential in dance.

How did you end up at UCLA?
A: In 1993, World Arts and Cultures sponsored some performances by Meredith Monk, a multimedia artist and the subject of my master’s thesis. I came to give some lectures before her shows. A year or so later, the department chair Judy Mitoma invited me back as a visiting assistant professor to teach dance history. And I never left.

How did the initiative “Make Art/Stop AIDS” start?
A: While teaching at UCLA, I got my Ph.D. in dance history and theory at UC Riverside and wrote my dissertation on dance in the AIDS era. My UCLA department was supportive of my developing a course on that topic. We named it “Make Art/Stop AIDS,” and it is still bringing together students from all across campus, many different majors. It’s amazing to see them begin to think of themselves as artists and then to think about putting their creativity into world-changing activity.

When did you take your program abroad?
A: As I was turning my dissertation into a book, I thought maybe I wouldn’t work on HIV and the arts anymore because it was exhausting. But then I read a newspaper article about fears that HIV was about to explode in India. I had spent considerable time in India after college and still felt connected to it. I began to wonder whether some of the things artists were doing here might be applicable in India, where there’s a long tradition of activist art-making. So I went there on a Fulbright to find the artists intervening in the AIDS epidemic.

With a grant from UNAIDS, my friend Rajeev Varma and I assembled about 60 Indian artists in Calcutta, plus some UCLA faculty and grad students. We called the gathering “Make Art/Stop AIDS.” That was the birthing for me of a movement in which artists would marshal their creativity to try to stop the AIDS epidemic.

To commemorate World AIDS Day 2014, the UCLA Art and Global Health Center is presenting an evening of art, performance, storytelling and media on Dec. 1 from 7 p.m. to 9 p.m. at Glorya Kaufman Hall, Room 200. There will be art exhibits, a special appearance by the UCLA Sex Squad, and a presentation of photography and real-life stories from “Through Positive Eyes,” a project in which people living with HIV/AIDS share their stories to fight stigma across the globe. Tickets are $6 and can be purchased here.  

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Filmy suppository could help in inhibiting HIV infection

NIH supports UC Merced-led research with $2.3M grant.

Biochemistry professor Patricia LiWang calls it a stroke of luck that she has become enmeshed in HIV research, but her developments are no accident.

The National Institute for Health (NIH) apparently agrees, awarding her more than $2.3 million over the next four years to continue working toward a new method of preventing HIV from infecting humans.

The developments coming from LiWang’s lab and her collaboration with three other universities could have global implications in the war against HIV and AIDS.

LiWang studies chemokines, signaling proteins that are secreted by cells. On their own they are HIV inhibitors, preventing the virus from binding itself to cells.

“But the natural ones in our bodies aren’t so great at it,” she said. “So we started working on the biochemistry to make them better.”

LiWang, with the School of Natural Sciences, thought there must be a way to improve the chemokines’ natural abilities through biochemistry, and began making several variants. She also started working on another inhibitor called griffithsin. But the big question when working with proteins is how to make them into medicine that can be used by people. They can’t be swallowed or the stomach would digest them, she said.

That’s when she got the idea to partner with a bioengineer at Tufts University in Massachusetts who designed a silk-protein film that could carry the HIV inhibitors to places in the human body that are most likely to be invaded by HIV – the reproductive and digestive tracts.

HIV preventatives have been tested in the forms of pills, gels and creams, and have been introduced in places like eastern and southern Africa, where HIV and AIDS are still at epidemic proportions.

However, refrigeration there is a challenge and the creams and gels aren’t popular with at-risk populations, so getting people there to use the inhibitors regularly has proved to be a problem. Gels and creams are messy and must be used every time someone engages in sexual activity that could transmit the virus.

LiWang’s team has come up with a different delivery system – an easy-to-use, filmy suppository that melts with body moisture and is stable for months, even when temperatures exceed 120 degrees. The team is working on making the inhibitor time-released, too, so people could use it biweekly or monthly, making it more likely they would use it at all.

Professor Satya Dandekar at the California National Primate Research Center, chair of the Department of Medical Microbiology and Immunology in the School of Medicine  at UC Davis, plans to test the inserts in macaques to see if the silk films – which are known to be nontoxic – cause any inflammation. HIV feeds on inflammation, so that is a side effect that would not be acceptable.

Meanwhile, a researcher at Imperial College in the United Kingdom is using human reproductive and digestive tissue samples to test the silk films, looking for the same issues.

“At the end of the day, the question is: Will this work in humans?” Dandekar said.

She’s excited to be part of the collaboration partly because it’s a novel opportunity to test the inhibitors on systems that are the closest to human systems possible, but also because AIDS originated in monkeys. She believes primate testing could hold the key to HIV inhibition.

“We’ve probably cured every kind of cancer in mice, but we can’t cure all those cancers in humans,” she said. “We need to use animal models that are relevant to humans, and the primate reproductive systems are very similar to humans – and most appropriate for evaluating preventative measures for infectious diseases.”

Many studies are carried out in test tubes and petri dishes, too, Dandekar said, but those also do not present the full picture of what is happening in the whole body.

“All of this is a precursor to human trials,” LiWang said. “If we are ever going to be lucky enough to make the leap to human clinical trials, we need to find the optimal protein, make sure the silk films don’t cause problems, find out how long they can be used and whether there are side effects and work on the time-release aspects.

“But this shows how important basic research is. This work could, eventually, help people.”

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South African ‘Mentor Mothers’ help improve perinatal health outcomes

Community-based interventions lead to better health outcomes in both mothers and children.

The Mentor Mother program trains women to provide health information and conduct home visits to pregnant women and to help the mothers raise healthier children.

The incidence of HIV infection in South Africa tops that of any nation in the world, with some 6 million of the country’s nearly 50 million residents infected. Sadly, young women — and particularly young pregnant women — suffer some of the highest rates of HIV infection. More than one-fourth of pregnant South African women are infected with the virus; in some communities, the infection rates are even higher.

But a new study conducted by UCLA’s Mary Jane Rotheram-Borus, the director of the UCLA Global Center for Children and Families at the Semel Institute for Neuroscience and Human Behavior, and her colleagues from Stellenbosch University in South Africa found that community-based interventions could improve the health of children in those contexts. A paper about the randomized controlled trial appears in the current edition of the journal PLoS One.

The study found that regular home visits of pregnant mothers, and later of those mothers and their infants, by specially trained lay community mothers from the “Mentor Mothers” program led to significantly better health outcomes 18 months later in both the mothers and their children.

The Mentor Mother home visiting program, developed by South Africa’s Philani Maternal, Child Health and Nutrition Project, has been in existence for the past 15 years. Mentor mothers are trained to provide health information and health intervention (such as a home visit), support mothers to improve healthy births, and to help mothers develop coping mechanisms that enable them to raise healthier children. The program currently operates at eight clinic sites in Cape Town and out of Zithulele Hospital, located in a deeply rural part of the country’s Eastern Cape region.

Among other outcomes, the study found that Mentor Mother home visits led to a 50 percent improvement by mothers in completing tasks designed to prevent mother-to-child transmission of the HIV virus, compared to mothers in the control group of the study who did not receive home visits, just clinic-based pre- and postnatal care. The virus-transmission prevention tasks included pregnant mothers knowing their own HIV status and asking their sexual partners to be tested; mothers taking anti-retroviral drugs for the six weeks prior to childbirth and during labor; babies receiving anti-retroviral drugs for at least six weeks, until they can be tested for the virus; and mothers using one feeding method (breastfeeding or formula) for the first 6 months of their infants’ life, and, when possible, exclusively breastfeeding.

In addition, the study found that mothers who received regular home visits breastfed longer and, among HIV-infected mothers, were more likely to breastfeed exclusively for six months.

“There also tended to be fewer low birth weight babies, a condition which results in life-long problems,” said Rotheram-Borus, the Bat-Yaacov Professor of Child Psychiatry and Biobehavioral Sciences and the director of the Center for HIV Identification Prevention and Treatment Services at UCLA.

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