Monkeys infected with a close relative of HIV can ramp up production of T cell that lowers resistance to viruses.

Barbara Shacklett (left) and Julie Shaw, UC Davis

Tissue in monkeys infected with a close relative of HIV can ramp up production of a type of T cell that actually weakens the body’s attack against the invading virus. The discovery, in lymph nodes draining the intestinal tract, could help explain how the HIV virus evades the body’s immune defenses.

If the same pattern is found in people infected with HIV, the finding could lead to a treatment strategy that slows the production of this restraining type of T cell. This would let the immune soldiers go after the virus more aggressively.

The scientists don’t know if the simian virus is directly causing the build-up of the inhibitory T cells, called regulatory T cells, but in any case, reducing regulatory T-cell production could boost the body’s resistance to the evasive virus.

The research was a collaboration among scientists at the UC Davis School of Medicine, Cincinnati Children’s Hospital and the California National Primate Center.

Regulatory T cells, or Tregs, normally tamp down immune-system attacks, presumably to prevent an over-active assault that can cause harmful inflammation or auto-immune disease. The scientists suspect that the high number of Treg cells in the infected primates might prevent their immune systems from mounting a full-on attack against the virus.

The researchers focused on immune cells called dendritic cells that interact with Tregs in preparation for their policing duty. This occurs in lymph nodes throughout the body’s lymphatic system — the part of the circulatory system that also drains many organs of fluids, fatty acids and other substances.

The study found that mature dendritic cells were particularly active in promoting Treg production, and that these promoters were in high concentration in nodes draining the intestine, or mucosa. The intestinal mucosa is the site of early infection and aggressive transmission for both the primate virus and HIV, making it the first line of defense against the invasion.

“The intestinal mucosa contains highly activated ‘helper’ T-cells that are prime targets for the HIV virus, so it is important to understand how the body fights HIV in this under-studied tissue,” said Barbara Shacklett, associate professor of medical microbiology and immunology at the UC Davis School of Medicine.

“We consider the GI tract as a major ‘battlefield’ between the immune system and HIV. If we can better understand what happens there, we may finally learn how to eradicate the virus,” said Shacklett.

Shacklett is a co-author of a paper on the research, entitled “Myeloid dendritic cells isolated from tissues of SIV-infected Rhesus macaques promote the induction of regulatory T cells,” published Jan. 28 in the journal AIDS. Julia Shaw, a graduate student in Shacklett’s lab, co-led the research with Pietro Presicce of the Cincinnati Children’s Hospital Research Foundation.

An editorial in the same issue of AIDS highlights the new research and related studies that are clarifying the interaction between the simian version of HIV and the Treg cells that can control attacks against them.

Shacklett stressed that Tregs usually increase when the immune system is at risk of over-reacting. Their high numbers lead to a reduced immune attack, although the mechanism is not well understood.

But in persistent infections — when a strong immune response is called for — Tregs should decrease in number, taking a “hands-off” approach and freeing the immune army to advance. HIV may sabotage this control by prompting increased Treg production as if the body need not rally its defenses against the virus.

The research draws on earlier research by Shacklett, Shaw and colleagues comparing Treg counts in rectal mucosa of people with high and low HIV viral load. They showed that high viral load was associated with increased frequencies of immunosuppressive Treg in the gastrointestinal mucosa, suggesting these Tregs might be thwarting the body’s immune defenses.

Other coauthors on the new research paper are Claire Chougnet, an associate professor of molecular immunology at University of Cincinnati College of Medicine, and Christopher Miller of the California National Primate Research Center.

The research was supported in part by the California National Primate Research Center’s Pilot Project award funded by BaseGrant NCRR-RR-000169 and the National Institutes of Health grants AI8227, AI068524 and AI057020.

The UC Davis School of Medicine is among the nation’s leading medical schools, recognized for its research and primary-care programs. The school offers fully accredited master’s degree programs in public health and in informatics, and its combined M.D.-Ph.D. program is training the next generation of physician-scientists to conduct high-impact research and translate discoveries into better clinical care. Along with being a recognized leader in medical research, the school is committed to serving underserved communities and advancing rural health. For more information, visit UC Davis School of Medicine at medschool.ucdavis.edu.

Research may improve performance of DNA detectors and aid diagnostics for HIV or cancer.

Kevin Plaxco (left) and Alexis Vallée-Bélisle, UC Santa Barbara

Over their 3.8 billion years of evolution, living organisms have developed countless strategies for monitoring their surroundings. Chemists at UC Santa Barbara and University of Rome Tor Vergata have adapted some of these strategies to improve the performance of DNA detectors. Their findings may aid efforts to build better medical diagnostics, such as improved HIV or cancer tests.

Their research is described in an article published this week in the Journal of the American Chemical Society.

Nature often serves as a source of inspiration for the development of new technologies. In the field of medical diagnostics, for example, scientists have long taken advantage of the high affinity and specificity of biomolecules such as antibodies and DNA to detect molecular markers in the blood. These molecular markers allow them to monitor health status and to guide treatments for diseases, including HIV, cancer and diabetes.

Kevin W. Plaxco, a professor of chemistry at UCSB, whose group carried out the research, notes that despite their great attributes, a main limitation of such biosensors is their precision, which is confined to a fixed, well-defined “dynamic range” of target concentrations. Specifically, the useful dynamic range of typical biomolecule binding events spans an 81-fold range of target concentrations.

“This fixed dynamic range complicates — or even precludes — the use of biosensors in many applications,” said Plaxco. “To monitor HIV progression and provide the appropriate medication, for example, physicians need to measure the levels of viruses over five orders of magnitude. Likewise, the two orders-of-magnitude range displayed by most biosensors is too broad to precisely monitor the concentrations of the highly toxic drugs used to treat many cancers. Our goal was, therefore, to create sensors with extended (for applications needing a broad dynamic range) or narrowed (for applications needing high measurement precision) dynamic ranges at will.”

The key breakthrough underlying their new approach came from the simple observation of nature. “All living organisms monitor their environments in an optimized way by using sensing molecules that respond to either wide or narrow change in target concentrations,” said Alexis Vallée-Bélisle, a postdoctoral fellow and the first author of the study. “Nature does so by combining in a very elegant way multiple receptors, each displaying a different affinity for their common target”.

Inspired by the optimized behaviors of these natural sensors, the UCSB research group teamed up with Francesco Ricci, professor at the University of Rome Tor Vergata to do their own mixing and matching of biomolecules to manipulate biosensors’ dynamic ranges. To validate their approach, they used a widely employed DNA-based biosensor used for detecting mutations in DNA called a “molecular beacon.”

By combining sets of molecular beacons all binding the same target molecule but with differing affinities, the international team was able to create sensors with rationally “tuned” dynamic ranges. In one case, they developed a sensor that monitors DNA concentrations over a six orders of magnitude range. In another example, they developed an ultrasensitive sensor that precisely detects small changes in target concentration over only a five-fold dynamic range. Finally, they also built sensors characterized by complex, “custom-made” dynamic ranges in which the sensor is insensitive within a window of desired concentrations (e.g., the clinically “normal” concentration range of a drug) and very sensitive above or below this “appropriate” concentration range. The researchers believe that these strategies can be in principle applied to a wide range of biosensors, which may significantly impact efforts to build better point-of-care biosensors for the detection of disease biomarkers.

This work was funded by the National Institute of Health, the Fond Québécois de la Recherche sur la Nature et les Technologies, the Italian Ministry of University and Research (MIUR) project “Futuro in Ricerca.”

Researchers call for increased screening for patients taking the the medication.

Tenofovir, one of the most effective and commonly prescribed antiretroviral medications for HIV/AIDS, is associated with a significant risk of kidney damage and chronic kidney disease that increases over time, according to a study of more than 10,000 patients led by researchers at the San Francisco VA Medical Center and the University of California, San Francisco.

The researchers call for increased screening for kidney damage in patients taking the drug, especially those with other risk factors for kidney disease.

In their analysis of comprehensive VA electronic health records, the study authors found that for each year of exposure to tenofovir, risk of protein in urine — a marker of kidney damage — rose 34 percent, risk of rapid decline in kidney function rose 11 percent and risk of developing chronic kidney disease (CKD) rose 33 percent. The risks remained after the researchers controlled for other kidney disease risk factors such as age, race, diabetes, hypertension, smoking and HIV-related factors.

For individual patients, the differences in risk between users and non-users of tenofovir for each year of use were 13 percent vs. 8 percent for protein in urine, 9 percent vs. 5 percent for rapidly declining kidney function and 2 percent vs. 1 percent for CKD. “However, these numbers are based on the average risks in our study population, and patients with more risk factors for kidney disease would be put at proportionately higher risk,” said principal investigator Michael G. Shlipak, M.D., M.P.H., chief of general internal medicine at SFVAMC and professor of medicine and epidemiology and biostatistics at UCSF.

[Related: Tenofovir: Q&A for patients and providers]

Patients were tracked for an average of 1.2 years after they stopped taking tenofovir. They remained at elevated risk for at least six months to one year compared with those who never took the drug, suggesting that the damage is not quickly reversible, said Shlipak. “We do not know the long-term prognosis for these patients who stop tenofovir after developing kidney disease,” he cautioned.

The implications for patients already on or starting antiretroviral therapy are “mixed,” said Shlipak. “The best strategy right now is to work with your health care provider to continually monitor for kidney damage. Early detection is the best way to determine when the risks of tenofovir begin to outweigh the benefits.”

Shlipak noted that HIV, itself, increases the risk of kidney damage, while modern antiretroviral treatments clearly reduce that overall risk. “Patients need to be aware of their kidney disease risks before they start therapy, and this should influence the medications that they choose in consultation with their doctor,” he said. “For an otherwise healthy patient, the benefits of tenofovir are likely to exceed the risks, but for a patient with a combination of risk factors for kidney disease, tenofovir may not be the right medication.”

Tenofovir is used to decrease viral load and increase immune cell count in people infected with the virus. It is currently considered the preferred first line treatment for HIV because of its potency, overall low toxicity, and convenience of dosing. It is sold under a variety of names, by itself and in combination with other medications.

The study examined the medical records of 10,841 HIV-positive veterans in the national VA health care system who were new users of antiretroviral therapy from 1997 to 2007. It was published electronically in the journal AIDS on Jan. 9.

Lead author Rebecca Scherzer, Ph.D., a researcher and statistician at SFVAMC and UCSF, said that the observational study was the largest and most conclusive indication so far of tenofovir’s association with kidney damage. “There have been a number of previous, smaller studies suggesting that this drug might be associated with kidney disease, but the results were mixed,” she said. “Those studies may have missed this association because they were too small, lacked appropriate lab data or excluded subjects with pre-existing renal impairment or risk factors for kidney disease.”

To be sure that tenofovir was the culprit, Scherzer and her colleagues looked for associations between 18 other antiretroviral medications and the same three measures of kidney disease:  protein in urine, rapid decline in function and progression to CKD. None were associated with higher risk.

Shlipak noted that the study results are particularly strong because two of the risk factors — decline in function and CKD — indicate kidney function, while protein in urine indicates physical damage to the kidney. “These are independent markers,” he said. “To see the same drug cause both types of kidney disease gives you a very objective signal that something real is happening here.”

Shlipak emphasized that, despite tenofovir’s association with progressive kidney disease, it is an important component of effective antiretroviral therapy that may be required in many patients to control viral load.

The VA is the largest provider of HIV care in the United States, said Shlipak. “We could not have done this work without access to the VA’s system of electronic medical records,” he said. “In particular, the data kept by the VA Clinical Care Registry, located at the VA Palo Alto Health Care System, were essential to this study.”

Co-authors of the study are Michelle Estrella, M.D., of Johns Hopkins School of Medicine; the late Andy I. Choi, M.D., M.A.S., of SFVAMC and UCSF; Steven G. Deeks, M.D., of San Francisco General Hospital; and Carl Grunfeld, M.D., Ph.D., of SFVAMC and UCSF.

The study was supported by funds from the National Institutes of Health, the National Center for Research Resources, the American Heart Association and the Department of Veterans Affairs, some of which were administered by the Northern California Institute for Research and Education.

NCIRE — The Veterans Health Research Institute — is the largest research institute associated with a VA medical center. Its mission is to improve the health and well-being of veterans and the general public by supporting a world-class biomedical research program conducted by the UCSF faculty at SFVAMC.

SFVAMC has the largest medical research program in the national VA system, with more than 200 research scientists, all of whom are faculty members at UCSF.

UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care.

Analysis of Kenya study shows simultaneously confronting AIDS, malaria and waterborne illness improves health.

A volunteer in 2008 shows people from the Lurambi District in Western Kenya how to use incecticide-treated bednets to prevent the spread of malaria

The great paradox of global health efforts is that regions of the world most plagued by poverty, poor infrastructure and rampant disease are often the most difficult to support. Now, scientists have demonstrated that confronting several diseases at once can make the most of thinly-stretched donor dollars and national health care budgets, to help to save lives.

A new analysis published this week in the open-access journal PLoS ONE (Feb. 3) focused on a combined public health campaign in Western Province, Kenya led by the Swiss-based company Vestergaard Frandsen, the Kenyan Ministry of Health and the U.S. Centers for Disease Control and Prevention (CDC). The analysis looked at the cost effectiveness of simultaneously confronting the problems of HIV/AIDS, malaria and diarrhea caused by waterborne pathogens.

The researchers used the results of the campaign to build an analysis of the impact such efforts could have if carried out more broadly. The analysis found that for every 1,000 people reached through such campaigns, some $16,015 in health care costs would be avoided and more than 16 lives would be saved. As a result, local populations would gain hundreds of years of healthy life. The cost would be $32 per person, but averted health care costs would be greater, leading to the net savings.

“That’s a very attractive deal,” said James G. Kahn, M.D., M.P.H., a professor of health policy, epidemiology and global health at the University of California, San Francisco, who is the senior author on the PLoS ONE study and led the economic aspect of the research. “This kind of a campaign is an excellent use of global health dollars.”

Health care workers distributed “CarePacks” at 37 locations in Kenya over seven days in 2008. These packs contained insecticide-treated bed nets to reduce the spread of malaria, water filters for preventing diarrheal diseases, and condoms.

Some 47,000 people ultimately received the packs, which also contained educational information as incentive for local residents to participate in a voluntary HIV testing and counseling program.

By combining efforts to reduce the burdens of malaria, diarrhea and HIV/AIDS, the program efficiently stretched the impact of its funds, Kahn said, which is important in areas where per capita health expenditures may amount to little more than a few dollars a year. Combining these public health efforts into one program also saved a great deal of time, he added.

“This program was implemented in seven days, reaching 80 percent of the local population,” Kahn said. “This rapid implementation means more health benefits were quickly achieved.”

Other co-authors of the article, “Integrated HIV Testing, Malaria, and Diarrhea Prevention Campaign in Kenya: Modeled Health Impact and Cost-effectiveness” are N. Muraguri, B. Harris, E. Lugada, T. Clasen, M. Grabowsky, J. Mermin and S. Shariff.

Kahn is based in the UCSF Philip R. Lee Institute for Health Policy Studies, the Department of Epidemiology and Biostatistics, and Global Health Sciences.

In addition to UCSF, authors on this study are affiliated with the Kenyan Ministry of Public Health and Sanitation, CHF International, the London School of Hygiene & Tropical Medicine, the ESP/UN Foundation, and the CDC.

The analysis was funded by the U.S. National Institute on Drug Abuse and by the company Vestergard Frandsen, which managed the campaign and manufactured the water filters and bed nets distributed.

UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care.

UC Merced biochemist is working to find a new way to block HIV.

Patricia LiWang, UC Merced

Patricia LiWang put two and two together last year. The UC Merced biochemist combined bits of two proteins to create the potential ingredients of a powerful new microbicide.

If all the kinks are worked out, and the ingredients make it into a tube and onto a shelf, they can block HIV from entering and infecting human cells in a sexual setting. Their potency is up to 100 times greater than existing HIV inhibitors. While most of the glamour these days is associated with vaccine research, LiWang is hopeful microbicides still have a chance in a world that needs every tool possible to prevent HIV infection.

LiWang grew up in a small working-class town in Pennsylvania and never knew she wanted to be a scientist until she went to MIT. “I thought I wanted to be an electrical engineer, because that’s what everyone did back then. Of course, they make you take a chemistry course for engineering, and I thought, wow, I really love this. I kept putting off the engineering courses and taking the chemistry courses,” she says.

LiWang went on to do research at the National Institutes of Health, and to professorships at Purdue and Texas A&M. Her husband does biochemical research on the mysteries of “clock” proteins, the timers in the human body researchers think affect when we wake and sleep, or even when a heart attack hits. “We have side-by-side labs,” says LiWang. “It’s very hard to get a job for two professors in same town, so we’re lucky to be at UC Merced.”

Read Q&A

See also this story about Patricia LiWang: UC Merced professor launches diaper drive to help the poor

UCSF-led research may reveal new ways to design future HIV/AIDS drugs.

Nevan Krogan, UC San Francisco

In perhaps the most comprehensive survey of the inner workings of HIV, an international team of scientists led by researchers at the University of California, San Francisco, has mapped every apparent physical interaction the virus makes with components of the human cells it infects—work that may reveal new ways to design future HIV/AIDS drugs.

Explored this week in back-to-back papers in the journal Nature, the survey reveals a pathogenic landscape in which HIV’s handful of proteins makes hundreds of physical connections with human proteins and other components inside the cell.

In one paper, the team details 497 such connections, only a handful of which had been previously recognized by scientists. Disrupting these connections may interfere with HIV’s lifecycle, and the existence of so many new connections suggests there may be several novel ways to target the virus.

“Have we identified new drug targets?” said Nevan Krogan, Ph.D., who led the research. “I believe we have.”

Krogan is an associate professor of Cellular and Molecular Pharmacology at UCSF and an affiliate of the California Institute for Quantitative Biosciences (QB3). He is also a faculty member at the UCSF-affiliated J. David Gladstone Institutes in San Francisco. Drawing upon the expertise of several laboratories that are world leaders in this area of research, Stefanie Jager, the lead author from the Krogan lab, collaborated with several other labs in the UCSF School of Medicine and the UCSF School of Pharmacy – including those of Andrej Sali, Alan Frankel, Charles Craik, Alma Burlingame, Ryan Hernandez and Tanja Kortemme – to carry out the global analysis.

In a companion paper, Krogan and collaborating labs of John Gross (UCSF) and Reuben Harris (University of Minnesota) investigated one such connection in detail. They discovered that an HIV protein called Vif makes a physical connection with a human protein called CBF-β, hijacking its function. This virus requires this action to function, said Krogan, which suggests that disrupting the connection may be a viable way to design new HIV/AIDS therapies.

“This is a good example of how biophysical studies can improve our understanding of disease and point the way to the exploration of potential therapeutic targets,” said Judith H. Greenberg, Ph.D., acting director of the National Institute of General Medical Sciences (NIGMS).

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Accomplished UC Irvine scientist and award-winning mentor.

Sheryl Tsai, UC Irvine

Most professors will say that they look at the “Rate My Professor” website with trepidation. It’s easy to get discouraged if a student complains that your grading isn’t fair, or you have dandruff or, even worse, that you’re boring.

Sheryl Tsai has no such fears. Her reviews are unanimous raves, and she has the teaching awards to prove it. “She’s hilarious,” writes one student. “She actually enjoys talking about biology with her students!” writes another.

An associate professor at UC Irvine, Tsai works in the hot new field of chemical biology, harnessing a compendium of scientific disciplines to the task of discovering new drugs.  In 2006, she was named a Pew Scholar for her research on the genetic modification of polyketides, natural products of plants, fungi and bacteria that can form the basis for new treatments for HIV, diabetes and cancer.

Her research has gained international recognition, but she’s just as proud of the teaching awards she’s earned at UC Irvine, including the prestigious Golden Apple Award for Teaching in the Biological Sciences. She mentors five or six students each year through UC Irvine’s Undergraduate Research Opportunities Program.

The UC Berkeley-educated Tsai grew up in Taiwan. (Her first name, Shiou-Chuan, informally became Sheryl after she arrived in the U.S.) By the time she was in high school, cultural and political ferment was loosening the grip of the island’s leaders and, as a result, Tsai says that when she arrived in Berkeley, the famously liberal city felt like home — almost.

Q: Your undergraduate and master’s degrees are from the University of Taiwan. Is university education different there?

A: Most of the professors have Ph.D.s from the United States, so it was very Americanized. Taiwan is a very open country with a big influence from the United States.  I grew up watching “The A-Team” every night.

Q: Berkeley isn’t exactly like the rest of America. Was it a shock?

A: Not really. I think the reason I felt comfortable at Berkeley was the emphasis on social justice. That year, the city of Berkeley increased parking fees, and to show their opposition, people knocked the heads of the parking meters off and planted flowers in them. Everywhere in the city, you saw flowers planted in the beheaded parking meters.

Amyloid fibrils in semen, shown here in red, enhance HIV infection by helping HIV — shown in green -- find and attach to its target, CD4 T white blood cells.

Breakthrough by Gladstone Institutes offers new hope in fight against global pandemic.

Scientists at the Gladstone Institutes have discovered new protein fragments in semen that enhance the ability of HIV, the virus that causes AIDS, to infect new cells—a discovery that one day could help curb the global spread of this deadly pathogen.

HIV/AIDS has killed more than 25 million people around the world since first being identified some 30 years ago. In the United States alone, more than one million people live with HIV/AIDS at an annual cost of $34 billion.

Previously, scientists in Germany discovered that HIV transmission is linked to the presence of an amyloid fibril in semen. This fibril—a small, positively charged structure derived from a larger protein—promotes HIV infection by helping the virus find and attach to its target: CD4 T white blood cells. In tomorrow’s issue of Cell Host & Microbe, researchers in the laboratory of Warner C. Greene, M.D., Ph.D., who directs virology and immunology research at Gladstone, describe a second type of fibril that also has this ability. Gladstone is affiliated with UC San Francisco.

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New programs that use HIV drugs to prevent infection can help reduce drug resistance when implemented properly, UCLA researchers say.

A new weapon has emerged to prevent HIV infection. Called pre-exposure prophylaxis, or PrEP, it is a strategy of providing medications to at-risk people before they are exposed to the virus. Having shown great promise in recent phase 3 clinical trials, PrEP may soon be rolled out for public use.

Because PrEP is based on the same drugs used to treat HIV-infected individuals, the big public health fear is that the dual use of these drugs will lead to skyrocketing levels of drug resistance. But in a new study, UCLA researchers say the exact opposite is likely to happen.

Sally Blower, director of the UCLA Center for Biomedical Modeling and a professor at the Semel Institute for Neuroscience and Human Behavior at UCLA, and colleagues used sophisticated computer modeling to determine that a PrEP prevention program used alone, or current HIV treatment programs used alone, could indeed, separately, increase drug resistance. But if used together, the researchers say, resistance is likely to decrease.

Their findings appear in the current online edition of the peer-reviewed journal Scientific Reports, published by Nature Publishing Group.

“This was a very big surprise,” said Blower, the study’s senior author. “We found that this counterintuitive effect will only occur if adherence to the PrEP prevention program, where individuals have to take a daily pill, is very high. This counterintuitive effect occurs when the beneficial effect of PrEP in preventing infections is so great that it overcomes both its own detrimental effect on increasing resistance and the detrimental effect of current HIV treatments on increasing resistance.”

Africa is ground zero for HIV and AIDS, a continent where the death rate is simply “awful,” Blower said. Since the country of Botswana was one of the sites for the PrEP drug trial, Blower and her colleagues chose it for their modeling. Botswana has the best health care system in Africa, they said, yet 30 percent of women and 20 percent of men are infected with HIV.

“Botswana is likely to lead the way in rolling out PrEP,” said Virginie Supervie, first author of the current study and a former postdoctoral fellow in Blower’s laboratory. “So officials there are worried about increasing levels of resistance.”

Most health officials feel that if you have a good treatment program in place, it makes sense to establish a good prevention program in the same place. Health officials plan to implement PrEP prevention programs only where treatment programs are highly successful and levels of resistance are low, the researchers said.

But in a second counterintuitive finding, the UCLA researchers say this conventional approach is actually the worst strategy. Instead, they suggest, PrEP programs should be rolled out around treatment programs that are having little success and where rates of resistance are high. Their model shows that this unconventional approach would prevent the maximum number of infections and result in the greatest decrease in drug resistance.

“By cutting down infections, the PrEP programs will decrease the number entering treatment programs, and therefore, fewer individuals will acquire drug resistance,” Blower said. “So introducing PrEP around the worst treatment programs will have the most impact on reducing resistance.”

A PrEP clinical trial that involved men who had sex with men and transgender women who had sex with men found that PrEP reduced the risk of acquiring HIV infection by 44 percent. Two other PrEP trials, which involved heterosexual men and women, showed significant reductions in risk, ranging as high as 73 percent.

“These results are very promising,” Supervie said. “Our model shows that if the roll-out of PrEP is carefully planned, it could decrease resistance and increase the sustainability of treatment programs. But if it is not, resistance could increase, and the sustainability of treatment programs in resource-constrained countries could be compromised.”

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From research to global outreach, UCSF commemorates three decades of AIDS.

UC San Francisco has been working for the past 30 years as a leader in AIDS basic and clinical research, patient care, policy development and community and global outreach – efforts that continue today. With World AIDS Day this week, UCSF commemorates three decades of AIDS.

Thirty years after the first cases of HIV/AIDS were reported in San Francisco, Los Angeles and New York, experts believe the epidemic has reached an important crossroads, where new infections can be warded off in a wide variety of ways. Read more.

As physicians working on the frontlines of HIV/AIDS since its start 30 years ago near retirement, UCSF is looking to attract and train the next generation of doctors to specialize in HIV/AIDS medicine. Read more.

A cheaper laboratory test that helps guide anti-retroviral drug treatment for people with HIV/AIDS may be just as effective as a more sophisticated test, a group of international researchers has found – a discovery that could be particularly important in rural Africa. Read more.

The New Generation Health Center, which seeks to reduce the number of unintended pregnancies and sexually transmitted infections among high-risk youth in San Francisco, is hosting a fundraiser on Dec.1 to support its community outreach activities. Read more.

Ellen Schell, R.N., Ph.D., director of International Programs for the Global AIDS Interfaith Alliance and an associate adjunct professor in the UCSF School of Nursing, reflects on the uphill battle to combat AIDS in Malawi, a tiny, impoverished country of 15 million. Read more.

For more information: View UCSF’s special package of AIDS stories, media coverage, timeline and historical facts

Related coverage:

• UC San Diego’s Douglas Richman discusses AIDS/HIV advances
• UCTV programs on AIDS/HIV

The gel could significantly reduce HIV transmission.

Peter Anton, UCLA

A topically applied microbicide gel containing a potent anti-HIV drug has been found to significantly reduce infection when applied to rectal tissue that was subsequently exposed to HIV in the laboratory, according to a new study by the UCLA AIDS Institute. The gel was also found to be safe and acceptable to users.

The first-ever phase 1 clinical trial of the rectal HIV-prevention drug known as UC781, a non-nucleoside reverse transcriptase inhibitor, is described in the current edition of the online journal PLoS ONE.

HIV in bloodstream at undetectable levels not associated with increased markers of inflammation or risk of death.

Phyllis Tien

Low level HIV viremia — the presence of HIV in the bloodstream at levels undetectable by standard tests — was not associated with increased blood markers of inflammation or coagulation, or with increased risk of death, in adults taking highly active anti-retroviral therapy (HAART) for HIV infection, in a study led by researchers at the San Francisco VA Medical Center and the University of California, San Francisco.

“This answers an important question in the HIV research and patient community, namely whether low level viremia is associated with persistent immune activation in patients being treated for HIV,” said senior investigator Phyllis C. Tien, M.D., an SFVAMC physician and an associate professor of medicine at UCSF.

Persistent immune activation can lead to inflammation and coagulation, which in turn can increase the risk of cardiovascular disease, clotting and stroke, said Tien. “We did not find that patients with low level viremia have increased inflammation and coagulation, which means that we need to focus on other possible mechanisms by which HIV increases inflammation and coagulation,” she said.

The study was published Wednesday (Nov. 2) in PLoS One.

Patients on HAART generally are monitored every three months, said Tien, with the goal of maintaining their virus levels below the limit detectable by standard tests — 50 to 75 copies of virus per milliliter of blood, depending on the test. However, she said, studies have shown that even among patients on HAART with low levels of virus, elevations in markers of inflammation and coagulation are associated with an increased risk of cardiovascular disease and death. Thus, she said, “researchers have been wondering whether circulating virus below the lower limit of detection might be associated with immune activation and inflammation.”

Tien and her team analyzed blood samples from 1,116 HIV-infected participants in the Study of Fat Redistribution and Metabolic Changes in HIV Infection, an ongoing nationally representative longitudinal study of HIV-infected adults in the United States — making it “the largest study to date to look at this question,” said Tien.

The testing was performed by Roche Molecular Diagnostics, which used a newly approved assay to measure the presence of virus below the clinically approved limit of 20 copies of virus per milliliter of blood.

“Contrary to presumptions in the field,” said Tien, the assay did not find that low level viremia was associated with elevated levels of IL-6, a marker of inflammation, or fibrinogen, a marker of coagulation. Furthermore, there was no association between any level of virus and the presence of C-reactive protein — another marker of inflammation — or increased risk of death.

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