Reports for NATAP

1st International AIDS Society (IAS) Conference on HIV Pathogenesis and Treatment

July 7-11, 2001 Buenos Aires, Argentina

Report 1 from IAS (Intl AIDS Society) Conference Buenos Aires July 7-11 2001
     Reported by Michael Norton, PA

Key Note Speeches: Opening Ceremony 1st International AIDS Society Conference on HIV Pathogenesis and Treatment

After a Buenos Aires winter day that included lots of sunshine and temperatures in excess of 60 degrees, the delegates gathered away from where the conference would take place in a large metal structure near an airport for the opening ceremonies. Except for the occasional noisy interruptions and the shacking of the structure when jets landed or took off, the delegates listened keenly to remarks from Argentine dignitaries and public health officials, from the conference host organizer Dr. Pedro Cahn, from the past and present International AIDS Society presidents, and 3 key note lectures.

I have chosen to focus on one of the keynote lectures. Dr. David Ho of the Aaron Diamond AIDS Research Center and Rockefeller University in New York City delivered this lecture. Dr. Ho's title was: Learning Basic Science from Clinical Trials. As is his usual style at these sort of conferences, Dr. Ho reviewed for the audience he and his collaborators predominant focus of the past decade: Viral and T-cell Dynamics with an emphasis towards Viral Eradication. A few of the important highlights are listed below:

• Review points, Dr. Ho emphasized prior to launching into his groups current work: It is estimated that the half-life of a free virion is 30 minutes. The number of virions produced per day ranges from 1010 1012 virions/day. And the T-cells produced per day in response to this viral infection ranges from 107 109 cells/day.
  
  
• Historically the published data, from at least two independent sources (Ho & Shaw), have shown the half-life of a productively infected T-cell to range from 0.9 - 1.5 days. Productively infected T-cells are the source of the overwhelming majority of virus seen in the plasma of a patient not on antiviral therapy. This pool is responsible for the first phase of viral decay seen when a patient begins therapy. Once again, historically, this first phase of viral decay, after the start of HAART, was complete after 7 14 days. At the time this original work was published, it was generally accepted that the HAART regimen chosen (RTV based) was as potent as possible leading to a maximum decay rate in this pool. In new work being done at the Aaron Diamond Center, Ho showed using a regimen of Tenofovir, Kaletra, efavirenz, and 3TC he was able to accelerate this first phase decay rate of plasma viremia into a steeper decline then had previously been described. In the patients on this novel regimen, the first phase of viral decay was now over in a range of 4 10 days. Ho stated that this work has implications regarding the half-life of a productively infected T-cells, which he estimated at .7 days, down from the previous estimate of .9 - 1.5 days.
  
  
• Also of note, Ho stated that one can only speculate about where the residual replication, found among patients who are aviremic by the currently available assays, is taking place.

Commentary: This work further confirms the inadequate potency of the current 3 drug HAART regimens in stopping viral replication. One can look at this work through both the eyes of a skeptic or optimist. A skeptic might argue that this is yet another nail in the coffin of curing someone from HIV. Arguably this productively infected T-cell pool, which is quite accessible to drugs, should have been the easiest to understand and purge of HIV. If our success here is limited, how can we ever expect to understand and possibly purge the long-lived and latently infected cells. Whereas an optimist might see that the scientific understanding of why we failed in our earlier attempts at cure are now fully open. That to date we've been relegated to utilizing inadequate therapeutics to rapidly and fully extinguish viral replication thus perhaps patients are constantly re-seeding long-lived and as well as latently infected cellular compartments. The optimist also likes the fact that the regimen used in this group, showing greater potency, contains 4 or 5 drugs depending upon how you count RTV but is a total of <10 pills per day and can be taken without regard to food on a twice per day dosing schedule.