POSITIVELY AWARE November/December 2012
Aware of the heart
People with HIV may develop heart disease earlier than HIV-negative individuals and they may also have a greater risk of dying from it, reported two separate research teams.
“[Our] study was done to evaluate whether or not HIV-positive patients were receiving the same consideration for cardiovascular disease by their health care providers as HIV-negative patients,” Charles Hicks, MD, of Duke University, wrote in a statement summarizing his team’s findings. “We hypothesized that if they were not, then coronary disease would be diagnosed later in the disease process—often after having already suffered a heart attack or developing unstable angina (impending heart attack)—rather than through earlier evaluation of chest pain or other symptoms.
“This is in fact what was found,” he continued. “54% of HIV-positive patients did not have coronary catheterization until the time of an acute coronary event, as compared to 34% of controls. Since the current quality of HIV treatment now allows most HIV-infected patients to live into old age, and given the concern that HIV itself and/or the medications used to treat it may increase cardiovascular risk, failure to aggressively treat cardiac risk factors and to identify heart disease early could have significant consequences for the growing population of HIV-infected persons.”
His team looked at first-time cardiac catheterization, or cath (insertion of a catheter, or tube, into a chamber or vessel of the heart, for either diagnostic or treatment purposes), in patients with unstable angina (chest pain) or suspected coronary artery disease (CAD).
The HIV patients were an average of 49 years old. This made it very difficult for the team to put together an age-matched control group for comparison purposes, because few HIV-negative individuals had a cath done around that age.
These patients, whether HIV-positive or negative, were already in stable care, with at least three medical visits in the previous year, “so we felt it wasn’t an access to care issue so much as failure to recognize the risk factors in HIV and the fact that the higher proportion of HIV patients with cardiovascular disease weren’t recognized until a coronary event was about to happen or already underway,” said Dr. Hicks.
The good news was that once CAD was diagnosed, HIV-positive patients received the same care as HIV-negative ones, such as bypass surgery or getting a stent. The patients came from Duke University and the University of North Carolina at Chapel Hill.
Daniel D. Pearce, MD, of Loma Linda University in Loma Linda, California, reported a higher rate of death for heart attack patients who had HIV compared to those who were HIV-negative. His team looked at the Nationwide Inpatient Sample, a huge national database on hospitalized people.
”We found the hazard ratio of dying was 1.83 times greater if you have HIV,” said Dr. Pearce. (A hazard ratio of 1.0 would be an equal risk between the two groups. A hazard ratio of 1.83 represents an 83% higher risk.)
Furthermore, 4% of the HIV-positive heart attack patients died vs. 2% of the HIV-negative ones.
Unlike Dr. Hicks’ team, Dr. Pearce’s group found inequality in the way people with HIV were treated. They were significantly less likely to get typical heart attack medications and procedures. The team looked at patients hospitalized for at least a day.
Dr. Pearce agreed with Dr. Hicks when he said that medical providers should be aware of these differences found in the HIV-positive population, an issue long raised by specialists. He noted various biological dysfunctions promoting heart disease which have been found in HIV-positive people, saying research looking at what causes these problems needs to continue.
There could be other concerns, as well.
“It could be a bias on the doctor’s part,” he continued, “like we had a bias against women and we weren’t treating women correctly, or it just could be some systemic thing or that HIV or the medications are causing them to be sicker and they won’t qualify for the intervention.”
He said the findings raise the question of having an echocardiogram earlier for HIV-positive patients or considering aspirin therapy for them, and Dr. Hicks urged medical providers to start considering heart disease in HIV-positive patients with chest discomfort. “Because the patients are young, we may not think of cardiovascular disease,” he said.
“We don’t want people to have the procedure after they’ve already had injury to their heart,” he added.
You can see a panel presentation with the two men, along with Kristy Kaiser, MD, of Georgetown University (who worked in Dr. Hicks’ study) at here.
Black people experience less viral suppression
A group of patients in France who became infected with HIV and then started on antiretroviral therapy (ART) early in the post-infection period have shown no signs of a resurgence of their HIV infection seven years after being taken off therapy.
“These results suggest that…antiretroviral treatment should be started very early after infection,” said Charline Bacchus, lead researcher of the study at the French National Agency for Research on AIDS and Viral Hepatitis (ANRS).
The patients in the ANRS EP47 VISCONTI cohort (known as the Visconti Cohort) have an extremely low reservoir of HIV in their cells similar to that of “HIV controller” patients. HIV controllers are those who are able to control their HIV infection without the use of ART for an extended period of time, and represent about one out of every 300 people who have HIV.
In the study, 12 patients started therapy within 10 weeks of infection, were on therapy for an average of three years, and were able to control HIV after an average of seven years off therapy. At a press conference Asier Saez-Cirión, one of the study investigators, said they were interested in finding out whether HIV controller status could be induced. He estimated that 5–15% of those treated early could eventually control HIV off therapy. But don’t stop those HIV meds just yet—not only would we need to figure out how to identify who would have this type of response to early treatment, but also get those individuals onto treatment immediately following infection. The other question one might ask is, could some of those in the study already have been HIV controllers to begin with? While the genetic alleles commonly associated with HIV controllers was not found in these patients there may be other factors playing a role, which researchers now are trying to uncover.
Another study looked at two men who had been infected with HIV for many years, on suppressive antiretroviral therapy (ART), and who underwent treatment of lymphoma via an allogenic (meaning foreign, or from another donor) stem cell transplantation. Both patients received a milder form of chemotherapy, known as the conditioning regimen, prior to transplant, which allowed them to stay on their ART during and after the transplant. One patient was on Atripla, the other on Isentress/Truvada. HIV was detectable in their cells immediately after the transplant, but the transplanted donor cells replaced the patients’ own lymphocytes over time. The amount of HIV DNA in their blood cells decreased and became undetectable, for up to two years now in one patient and three-and-a-half years in the other. CD4s declined in both patients initially, followed by a robust CD4 increase in one patient, and the stabilization and no further decline of CD4s in the other.
Unlike Timothy Ray Brown, the “Berlin” patient, who received cells that were resistant to HIV because they lacked the CCR5 receptor, these patients received cells that were CCR5+. It is believed that the antiretroviral treatment protected the donor cells from becoming infected, leading one researcher to refer to it as “a form of PrEP [pre-exposure prophylaxis] at the cellular level.” Further tissue sampling and analytic treatment interruption will need to be conducted to assess the full extent of the reduction of HIV in the reservoir.
At a press conference held the same day these two studies were presented, David Margolis, MD, University of North Carolina at Chapel Hill, was asked by a reporter about the media’s role in reporting on cure advances responsibly and accurately, while at the same time not giving too much hope or creating complacency.
“That’s your job,” said Margolis. “We are very careful about what we say [as researchers], and we’ve defined cure several different ways. Different kinds of cure and eradication mean different things to different people, and have different levels of value. Perhaps we should come up with a word, like ‘complicated-eradication-chemo-immunotherapy,’ to slow people down. But you can’t argue with the goal and you can’t get there without working on it—and I can’t say how long it will take.”
Long-acting drug in development
Complera, the newest single tablet regimen (STR), comprised of rilpivirine (Edurant) plus emtricitabine/tenofovir (Truvada), continues to hold its own. Previously, it had been shown to be non-inferior to Atripla, another STR, made of efavirenz (Sustiva) plus emtricitabine/tenofovir. This time, however, it has been shown to maintain an undetectable viral load (of less than 50 copies/mL) in people who were switching from a Norvir-boosted protease inhibitor (PI) combination.
These were 24-week results in nearly 500 individuals, of whom two-thirds were switched to Complera and the rest maintained on their PI regimen. Overall total cholesterol, LDL (“bad cholesterol”), and triglycerides decreased to a greater extent among those switched than on those maintained on their PI. The differences were statistically significant.
“We all know that regimen simplification improves quality of life,” said Frank Palella, MD, of Northwestern University when he presented these results from the SPIRIT study.
Also continuing to do well: the still investigational elvitegravir and dolutegravir, both integrase inhibitor medications (INSTIs). In 96-week results from Study 145, elvitegravir continued to be non-inferior (as it was in earlier 48-week results) to Isentress, the only INSTI currently on the market. Development of INSTI drug resistance was low (about 7%) and similar with both medications. The 700 participants in this study were treatment-experienced, so they were less likely to achieve undetectable viral load. Overall, 47.6% of the 351 participants on dolutegravir had undetectable viral loads, compared to 45% of those on Isentress.
In 48-week results from the SPRING-2 study, dolutegravir was as effective as Isentress, with 88% vs. 85% of participants in the two groups achieving undetectable viral load. The participants were treatment-naïve (first time on HIV therapy), See more dolutegravir news in Briefly.
Once-daily pills improve outcomes
The investigational drug cobicistat (COBI), which boosts drug levels (a “pharmacoenhancer”), was given with Reyataz plus Truvada and compared to Norvir-boosted Reyataz plus Truvada, a preferred regimen under U.S. treatment guidelines. In Phase 3 study results after 48 weeks, cobicistat-boosted Reyataz was non-inferior to Norvir-boosted Reyataz, with high rates of virologic success (viral loads of less than 50 copies per mL) and similar safety and tolerability. Nearly 700 individuals participated in Study 114.
“Cobicistat appears to be an effective drug for boosting protease inhibitor levels, with greater potential for co-formulation,” said presenter Joel Gallant, MD, MPH of Johns Hopkins University School of Medicine. He noted the various co-formulations of cobicistat with protease inhibitors that are in development. Moreover, he pointed out that, “[Norvir]-boosted Reyataz is known to be a lipid-friendly regimen and cobicistat is no different.”
“This is all good news,” said session co-facilitator Christine Katlama, MD, of Hospitalier Pitie-Salpetriere in Paris, “because all the drugs work and when they don’t work there is no resistance.”
Zinc finger gene therapy continues to show promise
Several sessions looked at abuses that put sex workers at risk for HIV—and we’re not talking sex.
Instead, it’s police actions around the world—including here in the United States—to confiscate condoms and to use them as evidence of prostitution that puts sex workers at risk for HIV. Advocates said the situation is such that many sex workers are afraid to carry condoms because of the police harassment this can cause. In fact, even outreach workers have been followed by the police so that sex workers can be arrested when they take the condoms offered. As advocates pointed out, it is not illegal to carry condoms. Rather, confiscation serves as another avenue of illegal detention and intimidation.
Moreover, criminalization of consensual sex work keeps workers under dangerous conditions. In the “Criminalizing Condoms and Sex Work” session, Acasia Shields, author of Criminalizing Condoms, a report from the Open Society Foundation, said, “Police routinely search sex workers to confiscate and destroy condoms. This affects their ability to practice safe sex and they know it.”
Of the U.S. sex workers surveyed, 52% said they were afraid to carry condoms because of fear of police harassment. Shields said other abuses include threats of arrest to exhort sex, and beating or raping sex workers.
Discussing the findings from the first national congress of sex workers in Bangladesh, Simon Risen, MD, MPH, PhD, of Save the Children, said, “Violence against female sex workers spreads far beyond individual incidents and factually is gender-based violence.” Among other recommendations, Save the Children in Bangladesh says behavioral change campaigns should be aimed at changing community perceptions and creating acceptance of sex workers in mainstream society, and that maternal and child services should focus more on issues related to sex workers.
Darby Hickey of the of the Best Practices Policy Project of Washington, D.C., said, “We think sometimes that countries like the United States are a world apart from countries like Bangladesh, but unfortunately, we face the same issues. It is about law and about policy change, but also about how police operate outside the range of law. So we need to change policies, holding police accountable, and address the wider societal indifference and downright hostility.” She said efforts to “rescue and save” sex workers should be called “arrest and abuse.”
In the session titled “The Oldest Profession: Is Sex Work Work?,” Naomi Akers said equating sex work with human trafficking is insulting and hurts both sex workers, who are targeted by raids, and victims of trafficking, who aren’t helped at all. “When you’re doing sex work, of course you see it as work. It buys you food and helps you take care of your family,” she said, calling trafficking “horrible.”
Deanna Kerrigan of the Johns Hopkins Bloomberg School of Public Health in Baltimore detailed findings of higher HIV risk among sex workers around the world, and said support for sex workers’ groups, as well as human and health rights is critical for all sex workers, including men and transgender people. Labor rights, the focus of the session, would help to eliminate stigma and discrimination and increase HIV prevention efforts for this group of workers, she said. Richard Howard of the International Labour Office (ILO) said, “Decent work [as outlined by ILO] should exist for all human beings, regardless of whether it’s legal or not, whether it takes place in a formal or informal environment.”
Underscoring the human rights issues affecting sex workers were protests against the U.S. Consulate for denying them visas to attend the conference.
In the final analysis, the sex workers movement advocates for decriminalization of sex work as the most important way of protecting their human rights.
“The epidemic is not driven by the lack of a pill or a gadget, the epidemic is driven by repression,” said plenary speaker Cheryl Overs, Senior Research Fellow at the Michael Kirby Centre for Public Health and Human Rights at Monash University in Melbourne.
She founded a sex workers’ rights organization in Australia in the ‘80s and the Global Network of Sex Work Projects in the ‘90s. She has worked in HIV policy and programming for male, female, and transgender sex workers in more than 20 developing countries. “And that brings me to law and policy,” she continued. “Sex workers from Sweden to Singapore to Swaziland all say that the greatest threat to their health and human rights is the law that makes it impossible to find safe places to work, and prevents them from having the same protections as other workers and other citizens.”
Reyataz and kidney stones
With an annual budget approaching $31 billion, the National Institutes of Health (NIH) is the medical research agency of the federal government and the largest source of funding in the world for medical research. The NIH is also a driving force behind AIDS and HIV vaccine research; 10% of the agency’s budget—$3 billion—goes toward HIV/AIDS, funding research conducted at academic, commercial, and private labs, as well as at NIH headquarters in Bethesda, Maryland.
Some 75 buildings are scattered throughout the 312-acre NIH campus. During the International AIDS Conference, the agency hosted a press tour of two of those buildings, offering a closer look at the role the NIH plays in clinical research and treatment.
Opened in 2000, the Vaccine Research Center is a five-story facility where research is done to find vaccines not only for HIV, but for influenza, Ebola virus, and other diseases that pose global health risks.
Gary J. Nabel, MD, PhD, director of the Vaccine Research Center, opened the tour, explaining how the facility serves as an “intellectual hub” by putting all the stages of vaccine research and development under one roof.
Basic research is first conducted to find a promising vaccine candidate. A vaccine is of little use, however, if it can’t be efficiently and safely mass-produced, so it undergoes test production for good manufacturing practices and quality control. From there, a successful candidate then goes to clinical trials to determine how safe it is for patient use. Results from the trials are reviewed in a series of assessments. If the vaccine candidate doesn’t pass this process with flying colors, it goes back to basic research, and the cycle begins again. The three-phase cycle can take 10–18 years for a would-be
vaccine to complete.
Nabel said that the search for a vaccine has been elusive, because, “HIV is constantly mutating, changing its genetic make-up and protein structure.”
“HIV is a sugar-coated virus,” Nabel explained. Sugars produced by the body are converted into proteins by the virus. “This makes it invisible to the body’s immune system, which does not perceive the virus as a threat.”
However, Nabel offered some perspective on the search for an HIV vaccine. Although it took 17 years to develop a vaccine against hepatitis B, he pointed out that a polio vaccine took 45 years.
“A vaccine is at least 10 years into our future,” Nabel said. “What we’ve learned is that HIV is a very crafty virus.”
While one or two vaccine candidates look promising, it will be at least until mid-2013 before an assessment can be made, and a little longer to evaluate more mature data, Nabel said. Even if a vaccine were discovered today, it would take at least four years of additional testing and evaluation before it could become publicly available.
Next stop on the tour was the Mark O. Hatfield Clinical Research Center, a hospital where 1,500 clinical trials for a variety of illnesses (including HIV/AIDS) are conducted. Opened in 2005, the Hatfield Clinical Research Center is connected to the Warren Grant Magnuson Clinical Center, built in 1953, to form the largest hospital in the U.S. dedicated to clinical research.
The Clinical Research Center has spawned numerous treatments, from the first pediatric chemotherapy to development of AZT, the first anti-HIV drug. The center houses an HIV clinic that treats 500 patients, only one or two of whom are ever in-patients.
Dr. Henry Masur is the research center’s Director of Critical Care Medicine, but has focused the major part of his career on HIV and its associated complications. Although a research institution, Masur said the clinic recognizes the importance of keeping HIV-positive patients connected to care. That’s why while half the clinic’s nursing staff is in research, the other half of the nurses are also case managers.
Hepatitis C is a major concern for people who are HIV-positive, Masur said. There are 3–5 million people who have hep C out of 314 million Americans. While the current standard of care for hepatitis C can sometimes be difficult to tolerate and only helps to clear the virus in about one-third to one-half of patients, recent advances have raised the cure rate to 75% and higher. Masur said advances in treatment look even more promising, comparing them to the advent of protease inhibitors and combination therapy for HIV that came in 1995.
As people are now living longer with HIV, Masur said the research center is beginning to look at aging and other complications. “We’ll soon be examining neurocognitive issues,” he said. “Beyond anecdotally, does it happen, and if so, what can we do to reverse it?”“Knowledge is bi-directional,” Masur said. “What we learn in the lab will help patients. But there is a lot we can learn from patients and put to use.”