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Rx for Survival — A Global Health Challenge

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Deadly Diseases

HIV/AIDS

On June 5, 1981, a weekly report from the U.S. Centers for Disease Control and Prevention described a disturbing trend: Doctors in the United States had begun to see an unusual number of rare cancers and pneumonias among homosexual men. It was the first warning of a new pandemic that would take millions of lives over the next quarter century.

Doctors at UCLA Medical Center had evaluated blood samples from some of these patients using a recently developed test that could count the number of immune system cells in the bloodstream. These tests revealed that all the victims had one thing in common: severely compromised immunity to all diseases. The cause of the abnormality remained unknown.

Initially referred to as gay-related immune deficiency syndrome (GRID), a name which immediately stigmatized the condition in the eyes of politicians and much of the public, the disease soon made its presence felt among two other sub-groups of the population: intravenous drugs users and hemophiliacs. By the following summer the condition had acquired a new official name: acquired immunodeficiency syndrome (AIDS).

This name change was more than a political correction; it was prescient. Over the next few years, aggressive medical detective work would reveal that this deadly condition, first recognized among gay males in a highly developed nation, was caused by a rapidly evolving, blood-borne virus that first invaded the human species in a very different context: the rainforests of West Africa, possibly in the central highlands, and probably during the waning decades of the colonial era just before World War II. Finally isolated in 1983 and confirmed in 1984, the newly discovered pathogen was given the name HIV, the human immunodeficiency virus.

How did this killer emerge and spread, and why was such a lethal development not noticed until decades later? It is likely that subsistence hunters were the first humans exposed to the virus. Inhabitants of the African forests, living off the land, often fed themselves and their families on "bush meat." Those handling the bloody carcasses of two of humankind's closest primate cousins, mangabey monkeys and chimpanzees, were unknowingly exposing themselves to variants of a virus very similar to HIV. Considerable genetic evidence now supports the theory that at least two variants of a simian immunodeficiency virus (SIV) successfully adapted themselves to human hosts at some point during the first half of the century, with the Chimpanzee SIV becoming the source for HIV-1, the most virulent strain affecting humans. The first confirmed hospital death from HIV infection has now been traced back to West Africa in 1959.

As to why detection of this killer took decades, the primary reason is that AIDS kills indirectly, rendering the body defenseless against other, opportunistic infections. In an equatorial setting, these maladies are many and varied, and in turbulent postcolonial Africa, modern health services were scarce, recordkeeping was inconsistent, and communication systems limited. The emergence of a new and deadly killer "behind the scenes" simply went unnoticed, allowing the virus to evolve.

How did it spread during this early phase? HIV as we now know it shows up in all bodily fluids of infected people, but only semen, blood, breast milk, and vaginal discharge contain sufficient quantities to transmit infection; saliva, tears, and sweat do not. The virus can't be passed, for example, through sneezing, sharing utensils, or kissing casually.

The HIV virus is readily transmitted, however, via unprotected sexual intercourse, be it heterosexual or homosexual, as well as through direct contact with infected blood. Mothers may also pass HIV to their unborn children or to infants through breast-feeding.

The earliest cases in the developed world, unrecognized at the time, struck individual medical missionaries, sailors, and transport workers returning from extended tours in Africa. HIV appeared in Europe and America after new African highways spurred in-country travel, and just as international travel exploded with the jet age. At the same time, changing mores, political activism, birth control pills, and widespread use of recreational psychoactive drugs all helped to unleash a sexual revolution in modern secular societies.

During the years when the pandemic first gained a foothold in America, Europe, and China, medical procedures also abetted transmission; they may have done so in Africa as well. Before accurate screening methods were developed, infected people who became blood donors unwittingly transmitted the virus to patients receiving hospital transfusions. This accounts for the early prevalence of AIDS among American hemophiliacs, who need frequent infusions of human blood products to keep their blood functioning normally.

Several factors make HIV so lethal. First and foremost, it is a retrovirus, a specialized type of virus that not only penetrates the defenses of host cells, but injects its own genetic material into their DNA via a process that makes frequent "mistakes." When the host cell's genetic machinery is turned on, it replicates the HIV virus instead of itself, and the "mistakes" ensure that successive generations contain many variants. Some fail to reproduce at all, but a select number turn out to be incredibly effective at hijacking the host organism and perpetuating their kind.

Second, the HIV retrovirus is superbly adapted to penetrating the very cells that normally function to suppress such viral attacks. These are the helper "T" cells of the human immune system that control key defensive responses. As HIV replicates and accelerates its own evolution, it also manages to destroy its most potent enemy in the human body.

Third, serious symptoms of this breakdown of the immune system can take years to reveal themselves. While a victim often experiences uncomfortable early signs of infection, such as fever, aches, and swelling of the lymph nodes in the neck, groin, or armpit, these soon pass.

During the long incubation period that follows, the victim may look and feel healthy, but he or she is highly infectious to intimate companions. In cultures where intravenous drug addiction is prevalent or relaxed norms of behavior encourage, or at least condone, sexual promiscuity, HIV spreads silently and quickly. This is also true in societies where traditional gender roles, extreme poverty, or widespread imprisonment permit individuals little control over their bodies as far as the sexual gratification of others is concerned.

Months or years may pass, but each victim's immune system will finally exhaust its resources. The "T" cell count will fall; the viral load will rise. Opportunistic infections will begin to take their toll, causing weight loss, fatigue, fever, diarrhea, respiratory problems, sores, and night sweats. Lethal infections, previously held in check, now move in to take over — perhaps latent tuberculosis, malaria, or one of the rare pneumonias and cancers first observed in the United States in the '80s. Often the nervous system and the brain itself are overwhelmed.

In 2004, 4.9 million people were diagnosed as being HIV positive, the most ever reported in a year. That brings the number of worldwide HIV-infected individuals alive today to approximately 39 million. It is estimated that more than 22 million people worldwide have died of AIDS-related causes thus far.

Of the 3.1 million deaths in 2004, 16,000 occurred in North America, with a disproportionate percentage of new infections occurring among African Americans, Hispanics, and teens.

By far the highest level of mortality is found in sub-Saharan Africa, where the disease first established itself decades ago. The unstable postcommunist societies of the former Soviet Union and impoverished sectors of India, China, and Southeast Asia provide prime breeding grounds for its further spread. Wherever there are large prison populations, networks of intravenous drug addicts, or cadres of commercial sex workers, risks remain especially high, and everywhere medical blood supplies must continually be tested rigorously.

Early hopes for a vaccine have gone unfulfilled. Fifteen years after the first CDC report, HIV/AIDS remained a fatal diagnosis, having claimed such well-known figures as actor Rock Hudson in 1985 and tennis star Arthur Ashe and dancer Rudolf Nureyev, both in 1993. By the mid-90s, researchers had discovered only one weapon against HIV/AIDS: the drug AZT. But as the virus rapidly evolved around that, research teams worked furiously to come up with alternatives.

The first truly successful therapeutic strategy was announced in the summer of 1996, at the Eleventh International AIDS Conference in Vancouver, Canada: HAART (highly active antiretroviral therapy), an approach featuring the simultaneous use of multiple antiretroviral drugs. Today, more than 25 drugs fight the infection, often given in a "cocktail" of three or four types of pills. Some medications help keep the virus from entering the host cells; others help prevent infected cells from replicating. Together they create a complex barrier the virus cannot easily penetrate.

There is still no known cure. HIV's retroviral DNA continues to lie latent within some cells in the body's immune system no matter which therapy is applied. The HAART regimen can suppress but never eradicate HIV's potential to destroy the body's defenses.

Furthermore, not only is HAART costly, but it must be maintained every day on a strict time schedule for as long as the patient lives. If not, HIV can once again evolve around one or more of the drugs being used, and that resistance can be transmitted to others.

In some sub-Saharan countries today, HIV infection rates range between one-quarter and one-half of the adult population, with millions of orphans — many of whom are HIV positive as well — left to fend for themselves. In an effort to prevent entire societies from imploding, the international community has rallied since 2000 to drive down or subsidize the costs of massive HAART programs in these nations, which often requires building up the basic public health infrastructure in these regions as well. Still, only about 12 percent of HIV-positive people worldwide now receive and take their needed medicines each day.

Meanwhile, the prevalence of HIV/AIDS may be accelerating the spread of other extremely problematic diseases, such as multidrug-resistant tuberculosis (MDR-TB). In Botswana, for example, where a very focused public health effort is now under way that incorporates close surveillance of patients, an estimated 37 percent of the adult population is currently infected with HIV. By the mid-1990s, Botswana had made great strides against active tuberculosis as a killer, but by 2002, 60 percent of the nation's tuberculosis patients were also HIV positive, and the percentage of patients resistant to one first-line TB drug had jumped more than 200 percent in seven years.

There are still no immediate prospects for a vaccine to prevent AIDS, nor for a medicine to cure it. Yet because AIDS normally passes from one person to another only through direct, intimate contact, behavior modification is a key means of prevention or at least containment. HIV testing, combined with monogamy, abstinence, the use of latex condoms during intercourse, and avoidance of shared hypodermic needles, all can impede the virus' progress.

As dark as the AIDS picture is now, there are causes for hope. In Uganda, a strategy known as ABC — A for Abstinence, B for Be faithful, and C for Condoms — has met with great success: The infection rate in the East African nation dropped from 21 percent to 6 percent in a decade. In Brazil, aggressive public health measures combined with a frank, practical attitude toward drug use and the varied sexual behaviors of human beings have also curbed the spread of the virus. And in Thailand, the government assists commercial sex workers in making sure they use condoms and receive regular testing for HIV.

A recent study has found, however, that an alarming 90 percent of HIV-infected people today do not know they are HIV positive. Clearly the first step toward widespread treatment and behavioral change is for those who are infected to know that they are. The World Health Organization is trying to make that procedure safer and easier through oral HIV tests that require only saliva. For those not yet willing to have themselves tested, however, knowing that HAART drugs will be continuously available at a cost they can afford if they do prove to be HIV positive, is essential.


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