Wall Street Journal 17 March 1993

As one of a small but growing group of AIDS heretics, I was very pleased to see that the recent National Research Council report on AIDS challenged the orthodoxy. It said that HIV infection and AIDS will remain limited to specific geographic areas and risk groups identified at the beginning of the epidemic: gay men and more particularly an ever-growing population of urban, drug-addicted, poverty-ridden, malnourished, hopeless and medically deprived people.

The political and social implications of the National Research Council report have received massive press coverage over the past few weeks. But it is the scientific and medical implications, unaddressed in the report, that are truly revolutionary. As the World Health Organization's working group on AIDS pointed out in 1984, if everyone is not equally susceptible to AIDS, factors other than HIV alone must govern who becomes infected and whether infection results in disease. This basic medical principle is as old as the germ theory of disease itself.

There is absolutely no doubt that some people are much more susceptible to HIV and AIDS than are others. Perhaps the most striking data concern female prostitutes in Western nations. Early in the epidemic, it was assumed that female prostitutes would become the vectors by which HIV and AIDS would be spread to the heterosexual community. A single, HIV-infected female prostitute might, it was thought, infect dozens of heterosexual men, and equal numbers of women through these men.

In fact, between 5% and 10% of female prostitutes are HIV-infected in major U. S. cities such as Los Angeles and New York. But there are two striking facts about these prostitutes. First, HIV-infected prostitutes, with only a few exceptions, are intravenous drug abusers. Cases of sexually acquired HIV among drug-free prostitutes are almost unknown. Second, in literally only a handful of cases are female prostitutes thought to have transmitted HIV to a client, and drug abuse by both the prostitute and the client has been documented in almost all of those cases.

In consequence, every major review of female prostitution by the medical authorities of Western nations has concluded that drug-free female prostitutes are not susceptible to HIV and are not, and will not be, the means of infecting the general population. Immunologically healthy individuals seem to be immune. This is hardly the behavior expected of a typical sexually transmitted disease.

Further evidence that AIDS is controlled by more than just HIV comes from studies of the development of disease following active HIV infection. The average time from infection to overt AIDS (based on studies of gay men and intravenous drug abusers) is 10 years. If HIV alone controlled AIDS, then about half of the people infected with HIV in 1983 should have developed AIDS by now, regardless of their mode of exposure. Yet this is not true of hemophiliacs.

It is estimated that 90%, or some 15,000, of the hemophiliacs in the U. S. were infected with HIV between 1981 and 1984. One would expect at least half of these hemophiliacs to have developed AIDS by now. But only 1,500 cases of AIDS have been recorded among hemophiliacs during the entire epidemic. Moreover, hemophiliacs under the age of 20 and those with less severe manifestations of hemophilia progress to AIDS at a fifth the rate of older and more severe hemophiliacs. If anything proves that HIV alone does not control the development of AIDS, this is it.

An even more striking fact is that, like female prostitutes, hemophiliacs have not become vectors for spreading AIDS into the heterosexual population. So-called secondary cases of AIDS, in which a person not in a primary risk group acquires AIDS from someone in such a group, constitute only 3% of all AIDS cases ever reported in the U. S. Cases of AIDS transmitted by hemophiliacs total only 104 (as of January 1992), and most of the affected individuals have documented assaults on their immune systems beyond HIV exposure.

Tertiary cases of AIDS are completely unknown. No documented case of AIDS exists anywhere in the Western world of a drug-free heterosexual who contracted AIDS from a primary carrier (for example, a hemophiliac) and then transmitted the disease to a healthy, drug-free third party. Again, this phenomenon is unparalleled in any previous epidemic.

The prostitute and hemophiliac data argue strongly for the conclusion that healthy, drug-free people do not get AIDS. The people who do get both HIV and AIDS have many additional immunosuppressive factors at work on them that predispose them to disease. These include:

• Semen-induced autoimmunity following unprotected anal intercourse.
• Blood transfusions or infusions of blood-clotting factors.
• Multiple, concurrent infections.
• Chronic use of recreational and addictive drugs.
• Prolonged or high doses of many antibiotics, antivirals and antiparasitics, anesthetics, opiate analgesics or steroids.
• Malnutrition and anemia.
• A particular type of autoimmunity, in which one part of the immune system is triggered to attack the same T cells that are the target of HIV in AIDS.

Every person with AIDS for whom there is sufficient documentation has some subset of these risk factors. Consider, for example, the immunologic risks of blood transfusion patients. It is often said that their only risk of AIDS is HIV. But they would not need a blood transfusion unless they were already at death's door. The blood that they receive itself suppresses their immune systems; the greater the amount of blood transfused, the greater the immunosuppression. If the blood contains HIV or other viruses, such as cytomegalovirus, Epstein-Barr virus, or one of the hepatitis viruses, there is additional suppression of the immune system.

Most people receive transfusions because they require surgery. Surgery and the anesthetics that accompany surgery suppress the immune system. So do the opiate analgesics (e.g., morphine) and the high doses of antibiotics that are very often prescribed afterward. In some cases, the transfusion triggers an immunologic civil war in which antibodies attack white blood cells. Individually, none of these factors would cause AIDS, but together they can prove deadly.

Similarly, drug addicts have many more immunologic risks than simply HIV acquired from shared needles. The drugs they use often suppress the immune system. Most addicts are concurrently infected with a variety of viruses, including hepatitis viruses; bacteria; and recurrent sexually transmitted diseases. The majority chronically abuse antibiotics obtained through their drug dealers, and are therefore much more likely than the average person to acquire drug resistant strains of infections, such as tuberculosis. Most have autoimmune conditions in which their antibodies target their white blood cells. Most are malnourished, some severely so, and do not have the nutrients required to mount an effective immune response.

Worse yet, if the blood transfusion patient or drug addict is pregnant, she may pass on not only HIV, but all of her immunosuppressive risks to her infant. The fetus, too, is exposed to the transfusion, the anesthetics, the drugs, the malnutrition, the viruses and sexually transmitted diseases, the antibiotics. It even inherits its immunity for the first few months of life from its mother, and therefore inherits impaired immunity if that is all the mother has to offer.

AIDS, in short, is more than just HIV. This conclusion is both scary, in that we must recognize that we have been addressing only part of the cause of the epidemic, and it is exciting, because it gives us new targets for controlling AIDS.

Recent reports indicate that eliminating risk factors for HIV-infected people can be more effective in preventing the development of AIDS than treating HIV. Swiss and Italian studies, for example, show that eliminating drug use and malnutrition among HIV-infected addicts slows their rate of progression to AIDS by an average factor of three to 10 compared with addicts who continue to abuse drugs. Many of the drug-free former addicts have remained healthy.

Similarly, purifying blood-clotting factors for hemophiliacs has been extremely beneficial. Blood-clotting factors normally are made from the blood of hundreds or thousands of donors and inevitably contain huge amounts of cellular, viral and other contaminants. The new ultrapurified or recombinant-DNA-produced factors have totally stabilized immunologic functions in all of the treated hemophiliacs. Many of these HIV-infected hemophiliacs have even had their immunologic functions return to normal.

Controlling the factors that make one susceptible to HIV and AIDS may therefore turn out to be easier and more effective than targeting HIV itself. This is the medical implication of differential susceptibility to AIDS. It is time we recognize its importance. *

Mr. Root-Bernstein is an associate professor of physiology at Michigan State University and author of "Rethinking AIDS," just out from Free Press.