The Weird Story of the Berlin Patient
The only case of a possible sterilizing HIV cure has been challenged today at the 2012 HIV resistance workshop: the patient, actually, could still be HIV infected!
Eveybody knows the story of the "Berlin patient" (see, in particular, several articles and an interview of him on this website).
As an American citizen he flew back to San Francisco 2 years ago after havin being "cured" in Berlin by Dr Hutter (first publication in the N Engl J Med in 2009, last one in Blood in December 2011).
But it came like a thunder this morning when Dr Steven Yukl presented his talk intitled "Challenges inherent in detecting HIV persistence during potentially curative interventions."
An enigmatic title that hides quite a weird story.
Note that coauthors of this abstract are: T Chun, MC Strain, J Siliciano, E Eisele, R Buckheit, YC Ho, JK Wong, MP Busch, G Hütter, DD Richman, RF Siliciano, SG Deeks.
Actually, most of these people repeated several experiments on this patient blood plasma, blood cells and rectal biopsies...
And the facts are these:
"A large volume apheresis was performed and 9 billion PBMCs evaluated for the presence of replication-competent virus. All wells were negative for HIV p24, indicating that the frequency of replication-competent HIV was therefore estimated to less than one infected cell per 1.4 billion CD4+ T cells. A repeat experiment in a second laboratory confirmed these findings. Using a variety of assays and approaches, very low levels of HIV RNA were intermittently detected in plasma, although sequence analysis of these variants were different from each other and different from those present before the transplant. Digital PCR for HIV DNA was negative for 1 copy per 2 million cells with a 95% confidence limit of less than 1.9 copies per million cells. Collagenase-digested rectal biopsy-derived cells were positive for very low levels of HIV DNA but not RNA; no sequence for confirmatory studies could be obtained. HIV antibodies levels were low and declined over the course of approximately 18 months."
Data were also presented showing that although this patient remained HIV seronegative, he still has antibodies again HIV at a very low level of detection, below the cutoff of current commercially available ELISA tests.
These data raise several questions that are not addressed in the abstract conclusion: "Although the subject has had intermittent evidence for HIV persistence in some assays in some laboratories, the extremely low levels of virus which were detected, while pushing the limits of sensitivity and specificity, and the inability to match sequence with the subject’s pre-therapy virus make it impossible to conclude that the subject remains HIV infected."
First, is that only a matter of PCR contamination or variability of tests at such low levels. I personnaly have serious doubts about this argument because Deeks group did not even mention this variability at last CROI when they reported that Disulfiram was able to exhibit an anti-latency effect, based on very small blips!
Second, it is strange to see that the different research teams do not have any data on soluble markers of inflammation, HIV in semen, or the tropism of the circulating strains...That is ongoing they answered.
Then, there are 2 other alternative explanations to this viral persistence during a "cure": one, the patient has never been cured and is a chimera, second, he has been cured but reinfected. In this direction goes the observation that rectal HIV DNA was negative when he was in Berlin, and now is positive. Also goes the fact that different circulating viral strains were isolated.
A terrific story if there is. It was amazing to see that Steve Yukl, the virologist who never met the patient was at the lectern without a bullet proof suit....and that Steve Deeks sat quietly at the back of the room, the one who currently follows the patient...
To be continued, like TV series say....
Key words: Berlin patient, HIV cure, HIV eradication