VANCOUVER, BC--The new more aggressive approach to HIV infection,
using antiviral drugs early and in combination, reflects not only
the availability of new drugs but also the application of new
thinking about HIV infection (see reports "Early Combination
Treatment May Provide HIV Control" and "Researchers
Propose New Treatment Guidlines for HIV"). Initial (primary)
HIV infection causes an acute flu-like syndrome that is followed
by years of relatively asymptomatic disease. This period of "clinical
latency" had been thought to reflect viral latency, but work
by David D. Ho, MD, and his colleagues at the Aaron Diamond AIDS
Research Center, New York, has shown otherwise.
In research done in collaboration with George Shaw, MD, of the
University of Alabama (Birmingham), Dr. Ho showed that HIV continues
to multiply wildly during the "latent" period, producing
about 10 billion new virus particles per day. Most are eliminated
by the immune system, leaving a net "virologic set point"
that remains relatively stable for years.
In his presentation at the 11th International Conference on AIDS,
Dr. Ho said that this steady-state level (which can be measured
as copies of viral RNA per milliliter of plasma) varies from individual
to individual and is predictive of long-term clinical outcome.
Risk of progression to AIDS within 5 years is 62% in patients
with viral loads over 36,270/mL but only 8% in those with viral
loads under 4,350/mL. The new approach to treatment aims to lower
the set-point in individuals with high viral loads.
Dr. Ho also suggested that eradication of HIV might be possible
if the virus were hit hard enough early and if antiviral therapy
were maintained for long enough. This will require action on two
fronts: the clearance of free virions from plasma and the removal
of virus-producing cells such as infected macrophages and CD4
Dr. Ho said that with aggressive antiviral treatment, clearance
of virus down to undetectable levels in plasma can be accomplished
in 1.25 days. Reducing new virus produced by the second "compartment"
to undetectable levels requires about 2 weeks.
This still leaves a considerable pool of infected macrophages,
estimated at 109. Dr. Ho estimated that, absent new sources of
infection, these cells would "burn out" in 30 to 120
weeks. "Even if our estimate is off by several orders of
magnitude, it would not have a major impact. If the pool of infected
macrophages is 100 times greater--1011 cells--they would burn
out in 37 to 146 weeks," he said.