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The Berlin Patient: The HIV Cure Case Report with a Name

Controversy has been stirring among scientists, activists, and the media during the past week due to developments in the case of the Berlin Patient, Timothy Brown. So far there have been a dozen or more reports that have interpreted new information in a variety of ways. Even expert researchers are not exactly sure what to make of these developments.

The controversy began with a poster and oral presentation of Brown’s case by Steven Yukl from the University of California San Francisco at the International Workshop on HIV & Hepatitis Virus Drug Resistance and Curative Strategies last week in Sitges, Spain. Yukl presented new findings from extensive tests to determine whether HIV eradication has occurred and to define the potential role of various viral reservoir measurements.

Brown became widely known as the only person cured of HIV after he received bone marrow transplants to treat leukemia. His doctor, Gero Hütter -- a hematologist with no special experience in HIV -- found a donor who was both a genetic match and had an uncommon mutation, known as CCR5-delta32, that makes CD4 cells resistant to HIV entry.

Over the last 5 years Brown has endured multiple high-volume blood draws, leukapheresis,flexible sigmoidoscopy with 30 biopsies from the rectum, and a lumbar puncture for this study. His blood plasma, peripheral blood mononuclear cells (PBMCs), and gut and cerebrospinal fluid (CSF) samples were sent to several labs with expertise in detecting extremely small amounts of virus. Researchers including Tae-Wook Chun from the National Institute of Allergy and Infectious Diseases, Douglas Richman from the University of California San Diego, and Robert Siliciano from Johns Hopkins used a variety of different measurements and techniques.

The results showed that Brown's CD4 T-cell counts remained fairly stable and were within the normal range. HIV genetic material was found in plasma by 2 of 4 labs at 3 different time points, and once in a rectal sample, but it was barely detectable by the most sensitive assays and was lower than levels typically seen in patients with viral suppression on antiretroviral therapy.

No HIV RNA or DNA was detected in Brown's CSF, and 2 labs with co-culture experience could detect no replication-competent virus in 9 billion PBMCs obtained through leukapheresis. HIV-specific antibody levels were detectable, but tended to decrease over time.

Furthermore, cloned HIV sequences bore little resemblance to each other or to pre-transplant virus. Even stranger, 2 sequences were almost the same as a common lab strain, suggesting possible contamination.

Like looking for a needle in a haystack, this intensive analysis provided a collection of evidence that investigators hoped would provoke discussion about what tests are useful in people with extremely low-level virus, thereby advancing cure research.

Unfortunately, one researcher -- Alain Lafeuillade from the Department of Infectious Diseases at General Hospital in Toulon, France -- has morphed the conversation into mockery by misrepresenting the results in a blog post on the HIV Reservoirs and Eradication Strategies reference portal and in a widely distributed press release.

Lafeuillade stated that "although HIV could have evolved and persist[ed] over the last 5 years, these data also raise the possibility that the patient has been reinfected. More studies are in progress to know if this seronegative HIV individual can infect other subjects if he has unsafe sex."

As Richard Jefferys from the Treatment Action Group in New York stated in an email, "It is not yet certain if the analyses that did show evidence of HIV genetic material are accurate or represent false positives, but if they do turn out to be accurate it would not be a surprise: HIV can infect multiple different cell types but can only replicate in some of them, and Brown did not have every cell in his body replaced."

Paula Cannon from the University of Southern California Keck School of Medicinetold HIVandHepatitis.com, "The important thing is that Timothy remains free of any replicating or infectious virus, that he continues to have no symptoms of being HIV infected, and that he continues to be in good health -- that he continues to be cured."

Jefferys' and Cannon's statements appear to represent the consensus of cure researchers and activists, yet it depends on what definition of cure is used. The field is so new, with so many unknowns, that what researchers mean by a cure is controversial in itself. However, if Brown is able to control HIV without medication, he is considered functionally cured, despite not being able to completely eradicate every last bit of non-replicating HIV in his body.

Lafeuillade's statement suggesting that Brown may infect other people if he has unsafe sex is "vile," "appalling," and "shameful," according to several AIDS cure activists. Debate is necessary in science -- especially when a field is new -- but when blatant misinterpretation demonizes the patient, the goal is crushed.

I've got to hand it to Timothy Brown, who is still the first person known to be cured of AIDS. As he eventually decided to make his name known to the world, he has had to live with scientific commentary and interpretation, accurate or not. He has had to endure countless tests and procedures, and at least one close call with death. Yet all along he has graciously allowed himself to be poked and prodded, volunteering his body -- his blood, sweat, and tears -- for some of the most important scientific research in the history of AIDS.

6/15/12