Surrogate Marked

The term "surrogate markers" crops up a lot when discussing HIV-AIDS research and the status of HIV infection in a patient. In short, surrogate markers are benchmarks for doctors to monitor the hypothesized progress from HIV to AIDS and the efficacy of the drug treatments they prescribe.

The two AIDS surrogate markers now in use are the "viral load" test and CD4 cell count -- also known as the T4 or T-cell count. The first uses new biochemical techniques like the polymerase chain reaction (PCR) to measure the activity of the virus. (Ironically, the inventor of PCR, Nobel Prize winner Kary Mullis, is an outspoken opponent of the HIV-causes-AIDS hypothesis.) The second tracks one type of cell in the body's immune system that often falls to dangerously low levels in AIDS patients.

However, the tests rely on as many unproven assumptions as the experimental drug therapies they purport to measure.

It is often assumed, for instance, that introduction of a therapy followed by a rise in CD4 count means that the therapy is successful. But, as Dr. David Rasnick of the University of California, Berkeley cautions, that same phenomenon happens all the time outside of AIDS-related medicine: "The CD4 cells are not being produced as a result of killing any virus. They're being squeezed out as the result of an assault to the circulatory system. It has nothing to do with the theory of HIV. It's a common phenomenon. You don't have to have AIDS or anything. If you get an injection, this will happen. If you take a pill this will happen. It happens to people who are healthy. If you have a drug, you will get a boost of CD4 cells."

The assumption that HIV kills CD4 cells, let alone that it causes AIDS, hasn't even been proven. (Three Australian researchers wrote a definitive critique of the hypothesized link between HIV and CD4 counts, which can be found on the worldwide web on the "Rethinking AIDS Homepage.")

Finally, the "viral load" test is still unproven in providing any useful clinical information about an AIDS patient. And yet it's frequently used in conjunction with protease inhibitors, the class of drugs now being touted as a major advancement in the treatment of AIDS. "Researchers are using an unproven test -- the 'viral load' thing -- to assess an unproven drug -- HIV protease inhibitors," Rasnick noted. "And they used HIV protease inhibitors in the same study to validate the test. It's a dog chasing its tail. Or as Don Abrams [Assistant Director of the AIDS Program at San Francisco General Hospital] says, it's like an M.C. Escher print. It's two hands drawing each other."

--Mark K. Anderson