Plagues in World History (28 page)

Eventually, full-blown AIDS emerges because the body, left helpless without a properly functioning immune defense system, is prone to opportunistic or secondary infections—far more deadly and aggressive than normal—which is what the AIDS patient usually dies from, rather than from HIV itself. Absent the intervention of some kind of antiretroviral therapy (ART), such cases of full-blown AIDS will typically appear within ten to twelve years from infection with HIV, although considerable variation within that time frame is possible.

Some patients can develop AIDS fairly quickly, within two years from infection due to contributing lifestyle factors (such as drug use) or coinfection with other blood-related illnesses such as hepatitis; but in 5 percent of cases certain “non-progressors” can go for a dozen years or more without manifesting AIDS, perhaps because their immune system is especial y good at fighting HIV or because they are infected with a less reproductive form of the virus. Once a patient does come down with a case definition of ful -blown AIDS, he or she has anywhere from six months (usually in Pattern II countries) to two years to live without treatment. Some of the more typical opportunistic infections in a case definition of AIDS include the fol owing: protozoan il nesses such as toxoplasmosis (which attacks and inflames brain tissue) and cryptosporidiosis (infecting the intestines, causing severe and prolonged diarrhea); fungal diseases such as
Pneu-mocystis carinii
pneumonia (PCP), cryptococcosis (a form of meningitis), and candidiasis (or thrush); and bacterial diseases, particularly tuberculosis. Many of these organisms are already present in the body but are usually kept under control by a normally functioning immune system. AIDS patients are also susceptible to cancers often caused by coinfection by a member of the herpes virus family, such as: Kaposi’s sarcoma, an otherwise rare skin cancer that produces purplish lesions or tumors on the body, similar to the disseminated intravascular coagulation (DIC) of septicemic plague; lymphomas or cancers that originate in the immune system that are caused by the Epstein-Barr virus (which also causes mononucleosis in young adults); and cytomegalovirus infection, which 138 y Chapter 6

commonly leads to blindness. Female patients also often contract cervical cancer. Most of these infections can be treated independently of HIV with antibiotics and chemotherapy; they are also specifically associated with simultaneous HIV infection, since they show up again and again in AIDS patients out of all the diseases to which a compromised immune system is potential y vulnerable.

Furthermore, HIV causes on its own some potential y life-threatening il nesses without help from other microbes. One is called AIDS-dementia complex, in which the patient suffers memory loss, headaches, disorientation, depression, personality changes, and other neurological symptoms due to the fact that HIV

hidden in macrophages can invade the cells of our brain. Finally, the patient will lapse into a coma and die; damage to the spinal cord and peripheral nerves can also cause paralysis and burning, tingling sensations or numbness in the extremities. A couple of other HIV-related conditions include HIV wasting syndrome (also known as “slim disease”), in which the patient suffers dramatic weight loss of 10 percent or more of total body mass, often accompanied by persistent diarrhea, high fever, night sweats, and loss of appetite; and lymphade-nopathy syndrome, whereby the patient suffers prolonged swel ings of the lymph glands in the neck, armpit, or groin, akin to the symptoms of bubonic plague but apparently not as painful.2

Transmission of HIV from person to person is now well understood and documented. Fortunately for us, HIV is a fragile virus that cannot long survive outside the host; therefore, it must be passed directly in certain bodily fluids from one contact to another. Since HIV is mostly present in blood, semen, vaginal secretions, and breast milk (while only present in tears and saliva in trace amounts), this means it can be spread through limited routes of entry into the body that can mostly be regulated by a conscious choice of social behaviors. The most efficient mode of transmission is transfusion of HIV-tainted blood, with a 90 percent infection rate, but since 1985 all blood products in the United States have been screened for presence of the virus (as detected by an antibody test), so this is currently a rare mode of transmission, at least in Pattern I countries. However, blood transfusions may still play a significant role in new HIV infections where screening is not affordable or practical, such as sub-Saharan Africa, and it has undoubtedly contributed to the historic spread of the virus prior to our scientific awareness of it. Some patterns of injected drug use can also mimic the transfusion method of transmission, such as when addicts share syringes with which they have pulled back the plunger to mix their blood with the drug (in order to make sure they have found a vein or that all of the drug is being injected). Reusing of injection equipment in poorer countries with limited supplies is also highly dangerous for the same reason, in that some amount of blood will remain in the syringe after each use. Worldwide, injecting drug users (IDUs) AIDS y 139

account for less than 5 percent of all HIV infections, indicating that this is a problem easily solved by disinfecting needles, where these have to be reused, but until quite recently it has remained the primary mode of transmission in Asia and Eastern Europe. On the other hand, accidental needlestick injury represents a rather low risk of infection, at 0.3 percent (or three out of one thousand incidences), perhaps because actual injection of syringe contents into the victim usually does not take place. Mother-to-child transmission (MTCT) either during pregnancy and birth or afterward by means of breast-feeding is likewise a highly contagious mode of HIV infection: it is estimated that a child has anywhere from a 25 to 50 percent chance of contracting HIV from its infected mother by such means, provided that neither is treated by antiretrovirals. Finally, there is unprotected sexual intercourse as a mode of transmission of HIV; compared to most other methods discussed above, it has a relatively low rate of infection, yet this can be highly variable depending primarily on the way the act is performed and with whom. Vaginal intercourse has the lowest rate of infection, at 0.33 to 1 per 1,000 exposures for men and 1 to 2 per 1,000 exposures for women, but if there are genital lesions due to accompanying venereal infections such as syphilis or gonorrhea, the rate can be much higher. Also, if one has multiple or even daily concurrent sex partners (as in the case of commercial sex workers or prostitutes), the risk of infection will greatly increase. These factors, of course, also hold true with anal intercourse (whether homosexual or heterosexual), which on its own has a much greater rate of infection, at 5 to 30 per 1,000 exposures, than vaginal intercourse, mainly due to the greater risk of trauma to the protective epithelial barrier against the virus (which can not only receive infection but also give it, since HIV-tainted macrophages can be present in mucosal linings). And yet, other sexually transmitted diseases (STDs), such as syphilis and gonorrhea, have an even greater risk of transmission during unprotected vaginal sex than anally passed HIV, at 20 to 40 percent per exposure.3 As we will see, MTCT and heterosexual transmission seem to be the norm in sub-Saharan Africa, while homosexual and IDU modes have historically been the most prevalent in Pattern I and III countries.

The usual strategy of combating an infectious virus like HIV is to develop vaccines, as has been done with smallpox and influenza. However, HIV presents an unusually challenging microorganism to vaccinate against, for both biological and some socioeconomic reasons. As we have already seen, HIV integrates its genome into the DNA of the host cell, where it can lie dormant or hidden for years safe from any antibodies generated by a vaccine. Once activated or triggered, HIV then replicates rapidly within the cell and thus mutates quite easily, making it a moving target for vaccination, much like influenza. There is also concern about whether inactivated HIV used in a vaccine could become active 140 y Chapter 6

again, as does indeed happen in people naturally infected by the virus. Another possibility is that an AIDS vaccine could harm the immune system just as much as priming it against HIV, since antibodies would have to mimic the same CD4

proteins that HIV binds to on T-4 cells and macrophages. Given these difficulties, some have argued for developing a “therapeutic” vaccine rather than a “preventative” one, which would stimulate the immune system to fight and eliminate the virus once it is established inside the body, thus preventing progression to the full-blown disease of AIDS rather than warding off HIV infection itself. This would also have the advantage of reducing the risk of person-to-person infection, including MTCT. But other difficulties besides biological ones have intervened to forestall HIV vaccine development: difficulty in finding animal models and human volunteers to undergo vaccine trials, length of time involved in demonstrating the efficacy of the vaccine, ethical questions with regard to control groups and conducting trials in poorer countries, and economic disincentives such as liability issues and threat of lawsuits, high costs of development, low rates of return in developing countries—where most of the vaccine market is currently located rather than in the more affluent West—and, after years of trying to find a vaccine, simple disillusionment and discouragement in the wake of failure.4

Nonetheless, a six-year trial that concluded in 2009 found that a combined vaccine that stimulated both a cellular T-4 immune response as well as an antibody response had a 26 to 31 percent effectiveness rate in preventing HIV infection, rekindling hopes that eventually a viable vaccine will be found.

Of more proven effectiveness to date have been ARTs that reduce the viral load in the blood. These include reverse transcriptase inhibitors (which interfere with the production of viral DNA), such as azidothymidine (AZT), also known as zi-dovudine or retrovir; protease inhibitors (which interfere with the assembly of the protein coat in new viruses); fusion inhibitors (which prevent HIV from fusing with a host T-4 cell); entry inhibitors (designed to prevent HIV from entering a host cel ); and cytokine-based drugs such as interleukin-2 that help stimulate the production of more T-4 cel s in the body’s race against viral replication. Usual y, a “cocktail” combination of such drugs is prescribed to AIDS patients who can afford it (at a cost of fifteen to thirty thousand dollars in the West) in order to circumvent the potential emergence of HIV resistance. As we wil see, this highly active antiretroviral therapy, known by the acronym of HAART, has greatly prolonged the lives of AIDS sufferers in Pattern I countries and transformed the disease into something that is stil chronic but manageable, instead of one that has invariably spelled impending death. ART has also demonstrated its ability to prevent MTCT. And yet, it must be emphasized that ART is not a cure for AIDS, because HIV will eventually and inevitably acquire resistance to any drug cocktail due to its mutating ability. It is for this reason that new drug therapies must con-AIDS y 141

stantly be devised for HIV—for example, at least ten nucleoside and nonnucleo-side reverse transcriptase inhibitors, such as nevirapine, are currently being marketed in addition to AZT—and why ART is now started only after an HIV-infected patient has become symptomatic, rather than administering it to one whose viral count is already low. Nonetheless, antiretrovirals have made hefty profits for the pharmaceutical industry precisely because they must be administered over long periods of time in ever-changing varieties, as opposed to vaccines that theoretical y confer lifetime immunity after just one dose. Now that al nine genes of the HIV genome have been mapped and identified, gene therapy may provide a promising alternative to drugs or vaccines in the future.5

Last but not least, we should consider the geographical origins of AIDS. This is a controversial topic owing to the stigma attached to any part of the world held responsible for giving birth to so dreaded a disease. We have already seen how, in the nineteenth century, India was blamed as the “home of cholera,” which naturally associated the perceived filthy living conditions of the natives with its fulminant diarrheal symptoms that were so disgusting, at least to Western sensibilities.

But there is also a biological and historical basis for making such identifications, which can help advance our knowledge of the disease and ultimately our ability to combat it. We have to remember that AIDS is still a very new disease in humans, especial y compared to other il s such as plague or tuberculosis that have been around for centuries. With time, the stigma attached to the endemic origin of AIDS in western and central Africa, which currently is still a topic that must be tiptoed around with caution at AIDS conferences, will fade. No one now thinks any less of Central Asia for being the probable origin of the Black Death; it is simply a historical question to be explored and elucidated. We are still coming to terms with living in a world marked by the presence of AIDS.

The scientific evidence for AIDS originating in sub-Saharan Africa is strong.

Much research has been done on the simian immunodeficiency virus (SIV) found in monkeys native to Africa. Three of the SIV strains isolated from chimpanzees have been found to be genetically very close to the three groups of the HIV-1

virus that cause almost all cases of AIDS in humans. (The M group alone is responsible for 99 percent of cases, while the O and N groups have been found in patients in Gabon and Cameroon in West Africa, exactly corresponding to the natural range of chimpanzees harboring the SIV strains.) It is therefore believed that HIV first crossed over into humans from chimpanzees, much like smallpox or influenza have historical y crossed from cows, birds, and pigs. Africa also holds the most genetic diversity of HIV anywhere in the world. It is the only region to contain all ten subgroups of the M version of HIV-1 as well as the most recom-binant strains of these subgroups, and an HIV-2 strain confined to West Africa is practically identical in its genetic makeup to that of an SIV strain found in local 142 y Chapter 6