Re: RE: Nick Bennett: Ho and Pantaleo 1 November 2004
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Nicholas Bennett,
Infectious Disease Postdoc/Clinician
Department of Pediatrics, University Hospital, Syracuse NY

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Re: Re: RE: Nick Bennett: Ho and Pantaleo

James Madigan and others;

Pantaleo as I recall looked at DNA provirus, in the paper in question. Ho's viral dynamics were based on RNA genomes, so were looking at virions and not provirus (any kind of RT-PCR will have RNA selection, DNA removal and in-built controls to ensure no contamination of that kind occurs). Ho also looked at cellular provirus, in the NEJM paper I referenced, but don't confuse that with the viral replication studies! Viral provirus level doesn't change a great deal after the reservoir is seeded.

Viral load is based on cell-free samples, so again any kind of HIV in lymphocytes should be removed.

The idea of HIV being an activated endogenous virus doesn't really work: there are so many studies comparing infected with uninfected people, tissues, cells...if HIV was present in the human DNA, we'd have found it by now. The fact that Pantaleo DIDN'T find HIV provirus in 75% of lymphocytes in nodes suggests that it can't be endogenous (and remember his work is just one in a whole lot of literature).

Hanz Gelderblom wrote to me with an estimation of how much virus should be present to get an EM of HIV from peripheral blood. He reckoned it would be about 10 billion per ml RNA viral load, and despite several years of attempts never got a sample of sufficient concentration to do that (this is detailed in an old BMJ Rapid Response). Conversely, EM's of HIV from lymph nodes and from cultured (i.e. amplified amounts of) peripheral cells can easily be done, as you suggest by your guess based on the levels of infected cells. The question is then whether you believe the LN and culture EMs. Most do, a few don't (e.g. the Perth Group) - but I can't see that there is a reason to discard that EM data.

As regards Mr Russell's statement: having offered to continue the discussion elsewhere, it's surely obvious that I'm willing to continue to try to explain things - not run away. And I would say that all of Mr Russell's questions have been answered (or explained) elsewhere in the RR's, just not to his satisfaction. So long as the thread remains open I will try to contribute, where I feel my points will be taken on board or the data is being misinterpreted. My hope is that the contributors and editors are more careful about what gets published, in case of gross misrepresentation to the public.

Nick Bennett njb35@cantab.net

Competing interests: None declared