New data on the Berlin patient: interpret with caution

Steve Yukl from UCSF presented new data on the case of Timothy Brown, the ‘Berlin Patient.’

Yukl described multiple experiments performed by several independent laboratories with the aim of searching intensively for any signs of residual HIV infection in plasma, peripheral blood mononuclear cells (PBMC) and biopsies from the gut and cerebrospinal fluid (CSF). The nature of these analyses is a testament to Brown’s extremely laudable willingness to undergo an array of unappealing procedures in order to advance research into curing HIV.

No infectious HIV was detectable in any sample (including samples containing huge numbers of cells). In most cases, no HIV RNA or DNA could be found either, but there were some exceptions: a minority of samples, analysed by some labs, intermittently tested positive for extremely low levels of HIV RNA. A very small proportion of the rectal samples also tested positive for very low levels of HIV DNA. Genetic sequencing results were not available but the abstract indicates that the RNA positive samples did not show any relationship with each other or the original infecting HIV (a finding perhaps suggestive of PCR contamination). Levels of antibodies against HIV have continued to decline over 18 months of follow up, while CD4 and CD8 T cell counts have reached near normal levels. The researchers make it very clear that because the assays being used are at the limits of their sensitivity and specificity, it cannot and should not be concluded from these data that Brown is still infected. Although it is possible that there is some residual virus present and that Brown is a case of a “functional cure” rather than complete HIV eradication (or “sterilising cure”), further work will be needed to explore that possibility. But it is far more likely that—as the study authors state—these new results are just evidence of the technological challenges associated with looking for miniscule amounts of viral genetic material.

Unfortunately, it is all too easy to envision the mainstream media picking up news of this presentation and wildly misinterpreting it (e.g. “Man Said Cured of HIV Still Infected!”). Alain Lafeuillade, who runs the biannual HIV Persistence Workshop and the HIV Reservoir Portal website, has not helped matters by writing a bizarrely misleading post on the study which suggests that the authors interpretation of the data is wrong and that Brown is either not cured, or—in an even stranger piece of speculation—that he may have been reinfected. The evidence supports neither claim.

In a related development, on 7th June 2012, the scientist Lawrence Petz held a press conference with Timothy Brown at a symposium in San Francisco on the use of cord blood to facilitate stem cell transplants. Petz revealed that around 100 cord blood donors homozygous for the CCR5 delta-32 deletion have been identified (out of 17,000 tested), and one HIV-positive individual in the Netherlands has recently received such a transplant as part of a course of treatment for another disease. Another similar transplant is to be performed soon for an HIV-positive individual in Madrid. These cases will be carefully followed to see if the beneficial outcome experienced by Timothy Brown can be duplicated.

Yuki SA et al. Challenges inherent in detecting HIV persistence during potentially curative interventions. International Workshop on HIV & Hepatitis Virus Drug Resistance and Curative Strategies, Sitges, Spain, 5-9 June 2012.