What’s Up with the Berlin Patient?

Timothy Ray Brown was cured of his HIV infection after receiving two bone marrow transplants, and is widely known in research circles as the Berlin patient. A recent conference presentation has some trying to make sense of the traces of HIV they've reportedly found in some cells of his body.

Brown, 45, had two bone marrow transplants in Berlin in 2007 and 2008 to treat leukemia, according to a recent report on NPR’s Morning Edition. The blood cells for the transplants came from a donor with a genetic mutation that makes his cells immune to HIV—they lack receptors the virus needs to gain entry to cells. The transplants appear to have snuffed out Brown's HIV infection. After an initial spike, the stubborn virus disappeared from his system, even though he is no longer taking anti-HIV drugs. Details about his case were published in the New England Journal of Medicine.

But on June 8 new data were presented at the International Workshop on HIV & Hepatitis Virus Drug Resistance and Curative Strategies in Sitges, Spain, which raise a question about whether there are minute traces of HIV RNA in Brown’s body. Researchers have combed through 9 billion of Brown's cells, retrieved from his blood, lymph nodes, spinal fluid, and intestinal tract. Four different labs could find no trace of HIV in his blood cells. But three groups, using tests at the very limit of detectability, think they have identified bits of HIV genetic material—two from blood plasma and one from intestinal cells.

It could be a false reading, due to laboratory contamination, scientists say. For one thing, the fragments of viral genes don't completely match those of the HIV Brown harbored before his transplants.

“Although the subject has had intermittent evidence for HIV persistence in some assays in some laboratories,” the researchers wrote in a summary, “the extremely low levels of virus which were detected, while pushing the limits of sensitivity and specificity ... make it impossible to conclude that the subject remains HIV-infected.”

Tae-Wook Chun, of the National Institute of Allergy and Infectious Diseases (NIAID) is one of the collaborators who found positive signals for HIV, but he stresses that no one isolated virus that could copy itself, and suggests Brown may simply harbor harmless, defective genetic pieces of the virus.

“We're pushing the limits of detection,” says Chun. “At the end of the day it's clear to us that he has some pretty low residual viremia. I don't really know what to make out of it, other than he's controlling viral replication or he doesn't have HIV that can restart the infection. It's a difficult case to talk about.”

Ideally, the researchers would have shown that the viral pieces they found matched the virus that was previously in Brown. But no such evidence exists. Chun and another collaborator, Robert Siliciano of the Johns Hopkins University School of Medicine, did sequence bits of virus they recovered, but the genetic codes did not match each other—or the virus found in Brown before his transplant.

Scientists at the University of California, San Francisco, who are following Brown most closely, declined to comment publicly, citing his confidentiality as a patient and research subject.

But researchers, and Brown himself, stress that even if the new findings constitute real evidence of HIV in his system, they don't mean he's not cured, though it may be a matter of what sort of cure he has. Scientists hoped Brown had a so-called sterilizing cure, which would mean the HIV has been completely eradicated from every cell in his body.

But long and bitter experience with HIV has shown that the virus can hide out in the genes of very long-lived resting immune cells. As these latently infected cells get activated over the years, HIV might reappear in the form of the whole virus or perhaps pieces of its genes.

If that is happening in Brown, there is no evidence that the virus is actively replicating. To do that, it would need to infect other cells and hijack their genetic machinery to crank out more virus. Since Brown's replacement immune system (from the bone marrow donor) doesn't have the entry portal HIV needs, these new viruses, if they exist, can't spark a new viral conflagration. Therefore, he may have a “functional cure,” even if he's not totally free of HIV.

But according to the NPR report Brown is distressed at the suggestion by some bloggers — in particular, a French AIDS researcher named Alain Lafeuillade of the General Hospital in Toulon — that he's not truly cured.

“It's not the case, but people are spreading it,” Brown told NPR. “That concerns me because I've been told by many people [who have HIV] that I give them hope…And that's what I want to do. I want to be able to continue spreading my message and be able to do that without having the conflicts of people who are misinterpreting the truth.”

Brown is particularly upset at suggestions that he has become re-infected with HIV through unsafe sex. “That is not the case,” he says. “It's very difficult for me to listen to those things and read those things.”

The latest findings are sure to be debated among AIDS researchers and advocates. Their main significance is to show how tricky it will be to determine exactly what constitutes a cure, as researchers devise various approaches to cure HIV/AIDS that are less drastic than bone marrow transplants. The question is, when can they be reasonably sure a cure has occurred?

For his part, Brown says he'll continue to be a guinea pig for as long as it takes if he can help resolve that big question.

“Hopefully one day I won't have to do it anymore,” he says, because he'll just be one of any cured patients. “That would be nice.”

In a report by Jon Cohen on ScienceInsider, Douglas Richman, University of California, San Diego, who chaired the session at the meeting that included Yukl's talk, says Lafeuillade "completely misinterpreted" a thoughtful presentation and subsequent discussion—and that it in no way challenges whether Brown is cured. "[Brown's] been off ARVs for 5 years," says Richman. "That trumps all these assays."

comment top

Obama Administration Urged to End Unfair Gay Blood Donation Ban

Leading members of congress, including Massachusetts Senator John Kerry and Illinois Representative Mike Quigley, have spearheaded a call to revise blood supply regulations that prevent thousands of healthy, willing donors from giving blood.  

In addition, A new petition from SignOn.org calls on Health and Human Services (HHS) Secretary Kathleen Sebelius, the Food and Drug Administration (FDA), Congress, and President Obama to lift the decades-long discriminatory ban forbidding gay men from donating blood, despite blood supply shortages and new tests that make the ban outdated and biased. 

June 14th is World Blood Donation Day.  However, only 5% of Americans are eligible and active blood donors. Despite shortages, a 27-year old policy bars men who have had sex with men any time since 1977 from donating blood. The policy, which was instituted at the height of the AIDS epidemic when no test existed to adequately identify the virus, disregards viable donations from thousands of healthy and willing donors, and ignores the rising rates of HIV amongst populations that are approved for blood donation, including heterosexuals and the elderly.  

Ryan C. Allen, an employee at United Blood Services, the nation’s second largest blood bank, started the petition on SignOn.org. Ryan is unable to give blood himself now because he is an openly gay man.

“Had it not been for those in her community that cared enough to donate their blood, I would not have grown up having a grandmother,” said Allen, who almost lost his grandmother due to complications from breast cancer surgery. “As I grew and continued to work on blood donation-related issues, I began to realize how severe the discrimination towards the LGBT community was in regards to donating blood. The ban on blood donation by gay males made some sense 30 years ago, when very little was known about the HIV/AIDS epidemic. But now, with 14 different tests applied to blood donations, the continued restrictions are biased and dangerous, withholding life-saving treatment from hundreds of Americans who would benefit from transfusions.”  

Earlier this week, Senator Kerry and Congressman Quigley sent a joint letter to Secretary Sebelius, applauding her request for more information on creating a pilot program to reassess blood safety criteria and beginning the process to lift the ban on gay blood donation.  In a statement, Senator Kerry thanked Sebelius for “taking this important step toward ending the lifetime ban on gay men donating blood, and instead relying on the science of today, not the myths of 20 years ago.”

In the letter, Kerry, Quigley, and other politicians who have since signed on, state, “Healthy gay and bisexual men continue to be banned for life, while the FDA allows a man who has had sex with an HIV-positive woman to give blood after waiting only one year. This double standard is inconsistent and indefensible. Our current policies turn away healthy, willing donors, even when we face serious blood shortages.”

Read the full petition from SignOn.org. Read the full letter from Sen. Kerry and Rep. Quigley here.

comment top

HIV Super-infection Rate Comparable to Initial HIV Infection

HIV super-infection may be as common as initial HIV infection and is not limited to high-risk populations, according to a new study led by researchers at the Johns Hopkins Bloomberg School of Public Health and the National Institute of Allergy and Infectious Diseases (NIAID). The results are featured online in the Journal of Infectious Diseases.

In the first large-scale study of HIV super-infection in a general heterosexual population, researchers examined the rate of super-infection among a community of sub-Saharan adults. HIV super-infection occurs when an HIV-infected individual acquires a new viral strain that is phylogenetically different from all other detectable viral strains. Super-infection can have detrimental clinical effects as well as accelerated disease progression, and increased HIV drug resistance even among individuals who were previously controlling their HIV infection.

“We found it remarkable that the rates of super-infection and underlying new HIV infections were equivalent. This raises many interesting questions about the natural immune response and its inability to generate resistance to HIV re-infection,” said Thomas Quinn, MD, MS, co-author of the study, an NIAID senior investigator, a professor with the Bloomberg School's Department of International Health and director of the Johns Hopkins Center for Global Health.

“For years there has been great debate regarding the rate of HIV super-infection among populations, and previous studies have focused on individuals exposed to the virus through high-risk sexual activity or intravenous drug use,” said Andrew Redd, PhD, lead author of the study and a postdoctoral fellow at the Laboratory of Immunoregulation at NIAID. “We were looking to determine the rate of HIV super-infection among a broader, general population using a novel technique sensitive enough to detect even the lowest levels of circulating HIV strains.”

Researchers, in collaboration with colleagues at the NIAID Rocky Mountain Laboratories, the Johns Hopkins Rakai Health Sciences Program in Kalisizo, Uganda, and Makerere University in Kampala, Uganda, used an ultra-deep sequencing technique to examine the blood samples of HIV-positive participants of the Rakai Community Cohort Study. Samples were tested at initial HIV diagnosis and at least one year later, prior to beginning antiretroviral therapy. The rate of super-infection was then compared to an estimated overall HIV incidence rate for HIV-negative individuals during this same time.

Of the 149 individuals tested, Quinn and colleagues identified seven cases of HIV super-infection during follow-up and all were initially infected with some variant of HIV subtype D. In addition, the rate of super-infection was comparable to primary HIV incidence in initially HIV-negative individuals in the general population in Rakai.

“These results also have significant implications for estimations of the age of the HIV epidemic and for phylogenetic modeling of viral evolution because many of these models assume that super-infection is not occurring,” suggest the authors. “In addition, the finding that super-infection is common and occurs within and between HIV subtypes suggests that the immune response elicited by primary infection confers limited protection and raises concerns that vaccine strategies designed to replicate the natural anti-HIV immune response may have limited effectiveness.”

comment top

Treatment Advocate Nelson Vergel to Appear in Oak Forest, Illinois on June 28

Nelson Vergel, renowned treatment, nutrition, exercise and personal fulfillment guru, will present “Living Well with HIV” on Thursday, June 28, from 6:00—8:00 pm at the Oak Forest Health Center. The event, sponsored by the South Suburban HIV/AIDS Regional Clinics (SSHARC), will take place at 15900 S. Cicero Ave. in Oak Forest, Illinois, Building H, 2nd floor Teleconferencing Room.

Positive for 25 years, Vergel is living proof that HIV-positive people can live long, healthy lives by learning how and what to eat, do, and feel in order to get the high-quality life they want. Vergel is the author of Testosterone: A Man's Guide, What You Need to Know About Your Man's Testosterone, and Built to Survive. He is also a frequent contributor to Positively Aware, most recently featured in the Summer 2012 issue, where he is quoted as saying, “My life has been enriched ever since I came out of the HIV closet and started helping others through my work…”

Be inspired by his example and learn how to live your best life with HIV. This event is free and open to the public.

comment top

Photo:Joshua Thorne

FDA Postpones Review of PrEP

In a June 6 email to stakeholders, Gilead Sciences announced that the FDA has extended the target date for its review of Gilead’s application for a prevention indication for daily Truvada (emtricitabine/tenofovir). Originally set for June, a decision regarding approval is now expected by September 14.

Gilead reported that the FDA clarified that the extension allows the agency to complete a detailed review of Gilead's revised Risk Evaluation and Mitigation Strategy (REMS), which reflects changes discussed with the agency after the Advisory Committee meeting on May 10.

Gilead’s proposed REMS for Truvada as PrEP was discussed at length at the May 10 meeting of the FDA’s Antiviral Drugs Advisory Committee, a webcast of which is available here. At the conclusion of that meeting the advisory committee recommended approval for Truvada as PrEP among HIV-negative adult men and women and that FDA pay close attention to the information and strategies in the label language and the REMS.

In a May 17 letter to the FDA, over three dozen HIV/AIDS and health organizations from across the U.S. urged prompt approval of daily Truvada as PrEP, as well as a number of marketing and implementation recommendations.

comment top

©IAS/Marcus Rose/Workers’ Photos

©IAS/Marcus Rose/Workers’ Photos

Organizers of the XIX International AIDS Conference (AIDS 2012) announced on June 13 that President Bill Clinton, South African Health Minister Aaron Motsoaledi, philanthropist Bill Gates, and humanitarian Sir Elton John, will be among the high-level speakers who will join thousands of the world’s top AIDS researchers, community leaders, and other stakeholders in Washington, D.C. this summer.

An estimated 25,000 attendees are expected to attend AIDS 2012, which will take place from July 22 to 27 under the theme Turning the Tide Together. This biennial event is the world’s largest meeting on AIDS, where leading scientists report on the latest AIDS research, and together with implementers, community leaders and policymakers, help to identify next steps in the global response to AIDS.

President Clinton will deliver keynote remarks at the closing session on Friday, 27 July. Sir Elton John will deliver a keynote address on Monday, 23 July.

“We are delighted to welcome the world’s leading AIDS scientists to AIDS 2012, and to have secured these high-level keynote speakers at this crucial time in the global response to HIV,” said Elly Katabira, International Chair of AIDS 2012 and President of the International AIDS Society (IAS).

The theme of AIDS 2012, Turning the Tide Together, has been selected to emphasize how a global and decisive commitment is crucial to change the course of the epidemic now that science is presenting promising results in HIV treatment and biomedical prevention.

“AIDS 2012 represents a unique occasion to mobilize policy makers, governments, NGOs, scientists, people living with HIV and civil society to join forces,” said Dr. Diane Havlir, U.S. Co-Chair of AIDS 2012 and Professor of Medicine at the University of California.

“Despite the global turbulent economic climate we cannot miss this historic moment, and it is vital to continue to attract funding to invest in AIDS research and promote programs based on effectiveness and efficiency in order to optimize the use of resources,” concluded Havlir.

The full AIDS 2012 programme is now available through the conference website and significant parts of the program, including webcasts of key sessions, speeches, slide presentations, abstracts, digital posters, session-specific and daily rapporteur reports, as well as workshop handouts and audio recordings, will also be online during the conference.  

Positively Aware Editor Jeff Berry, Associate Editor Enid Vázquez, and Art Director Rick Guasco will be reporting, posting, and tweeting from the conference.

Get conference updates and share your thoughts and ideas by tweeting @aids2012 or using #AIDS2012. Become a fan of AIDS 2012 on Facebook. If your group or organization is participating in AIDS 2012, post photos and videos of your work on this page.

comment top

Appeals Court Rules that HIV-Positive People’s Saliva Not a "Deadly Weapon"

A panel of judges on the New York Court of Appeals has unanimously overturned a lower court and ruled that if an HIV-positive person spits on or bites somebody, his/her saliva cannot be considered a "deadly weapon or dangerous instrument," as it had been deemed before. (See Sean Strub’s article “Prosecuting HIV” in the May+June issue of Positively Aware.)

David Plunkett was serving a 10-year sentence for punching and biting a police officer in 2006. Plunkett reportedly had a history of mental illness and assaulted one of the responding officers while causing a disturbance as a patient at an Ilion clinic.

In New York, in order for assault to become aggravated assault (which carries a greater penalty), the use of a deadly weapon or dangerous instrument is required. The original judge considered HIV-positive saliva a deadly weapon, making biting an aggravated assault and Plunkett pled guilty to both charges.

However, on June 7, the court dismissed the aggravated assault conviction, stating saliva should be treated the same as teeth, which in 1999 were deemed not to be dangerous instruments on the grounds that body parts come with the person and thus do not increase criminal liability.

comment top

Legislation Watch

Well, we’re all still holding our breath, waiting for the Supremes to issue their ruling. Word from The Hill is that neither Republicans nor Democrats have a plan for what comes next if the Court strikes down either the mandate alone or the whole law in its entirety. Hopefully, there will be a flood of press releases, letters, emails and phone calls from single-payer advocates letting them know what the next plan should be. For sure, DUH will be making some noise!

In the meantime, some co-sponsors were added to some of our favorite legislation.

HR 1116, the Respect for Marriage Act, repealing DOMA, gained Michigan’s Democratic elder statesman John Dingel, Missouri Democrat Russ Carnahan, and Ohio Democrat Marcy Kaptur.

HR 4470, the Routine HIV Screening Coverage Act of 2012, gained its 39th co-sponsor in New York Democrat Elliot Engel.

comment top