'Berlin Patient' case stirs controversy

  • by Liz Highleyman
  • Wednesday June 20, 2012
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New data about the "Berlin Patient" presented at a conference this month sparked controversy among researchers and advocates about whether Timothy Brown �" known as the only person to be functionally cured of HIV �" might still carry the virus.

Brown, who now lives in San Francisco, appeared to be cured of HIV after he received bone marrow transplants to treat leukemia while living in Germany. His doctor, Gero Hutter, found a donor who was both a genetic match and had an uncommon natural mutation, known as CCR5-delta32, which protects CD4 T-cells from HIV infection by deleting coreceptors that most strains of the virus use to enter cells.

Brown stopped taking antiretroviral drugs the day before his first transplant in 2007. Five years and many tests later, he still had no detectable HIV in his blood, CD4 cells, gut, or cerebrospinal fluid.

In an effort to learn more, Brown's fluid and tissue samples were sent to several researchers with experience using ultrasenstive tests to detect extremely small amounts of virus, including experts at the National Institute of Allergy and Infectious Diseases, Johns Hopkins, and UC San Diego and UCSF.

In early June, Steven Yukl from UCSF presented preliminary findings from this research at the International Workshop on HIV and Hepatitis Virus Drug Resistance and Curative Strategies in Sitges, Spain. The data he reported were inconsistent, demonstrating the difficulty of finding tiny amounts of virus at the limits of detection of current tests.

Two laboratories were able to detect very small amounts of HIV RNA in plasma, but two others did not. One lab found HIV DNA in a rectal biopsy sample, but none was detected in spinal fluid. No replication-competent virus could be detected in more than nine billion T-cells collected via apheresis. Brown's HIV-specific antibody levels were detectable but tended to decrease over time. His CD4 cell counts remained fairly stable and within the normal range.

Sequencing of the few detected bits of viral genetic material showed that they were not similar to each other, nor to the HIV strain Brown carried before his transplants. In one case the sequence matched a strain commonly used in lab tests, suggesting possible contamination.

The researchers concluded that Brown's treatment "has led to viral control ... and possibly eradication of replication-competent HIV ... although the intermittent detection of low-level virus raises the possibility that there has not been complete eradication ... [t]he combination of plasma, blood, and mucosal measures of HIV nucleic acid may not be sufficient to prove or disprove cure."

Despite this noncommittal conclusion, some media reports have implied that Brown still had HIV. One researcher, Alain Lafeuillade from General Hospital in Toulon, France, suggested in a blog post and press release that Brown may have persistent HIV or may have been reinfected; he also speculated that Brown might be able to infect others if he has unsafe sex.

Yukl declined to speak with most reporters due to patient confidentiality, but he did tell Science magazine that at this point "we can't say for sure whether there's been complete eradication of HIV," adding, "[t]he point of the presentation was to raise the question of how do we define a cure and, at this level of detection, how do we know the signal is real?"

"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," Paula Cannon from the University of Southern California told http://www.HIVandHepatitis.com.

Advocates expressed chagrin that Lafeuillade not only publicly misinterpreted other researchers' data, but also inappropriately speculated about a patient's personal life and behavior, which could discourage others from participating in future studies.

"I am not a physician or a medical scientist, but I am told that there was virus found in my blood that was tested to see if it was able to replicate, and there was no replication," Brown told the Bay Area Reporter. "I am still cured. I still do not have to take any medication at all."

"At this stage in cure research it's difficult to define what scientists mean by an actual cure," said treatment advocate Matt Sharp. "As a person with AIDS, if my body could control any level of virus without antiretroviral drugs, I would consider that an incredible advance in science, no matter what it's called."