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 lymphocytes.
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.