By Ali Haider

Epidemiology

The Human Immunodeficiency Virus (HIV). Perhaps the most infamous virus in medical history. It is the cause of a disease for which there is no cure, and whose natural history is ultimately death. That disease is AIDS (Acquired Immunodeficiency Syndrome). Twenty long years of physician experience and expertise, millions of government funded dollars, and endless man-hours of research later, the resilient HIV evades our efforts of eradication, and continues to flourish. It cleverly uses our very own vices against us--sex and drugs--to propagate and survive among our species. However, controlling those risk factors often proves more challenging than fighting the virus itself. A lot of progress has been made since the days of Philadelphia, but there are long roads that have yet to be travelled and many goals that await in our fight against HIV and AIDS, not only in the U.S., but across the world. Here I will attempt to give a rundown of a little history, science, and future of this disease.

Lets take a look at some numbers. In the United States alone, over 1 million people are walking around infected with HIV today (though the actual number I feel is higher). Worldwide, the number is an astonishing 40 million! Most of this number is contributed by populations of indigent populations, particularly in Africa, where access to education and health care is severely lacking. Each day, there will be 14,000 newly infected people across the world, almost 2000 of which are children under 15 years of age! Last year, there were about 3 million deaths related to the virus, and this trend is likely to continue in the coming years.

Pathophysiology

First some brief definitions. HIV, the human immunodeficiency virus, is what causes AIDS (adult immunodeficiency syndrome). It is designed to infect a certain type of white blood cell, CD4+ helper T cells, which are key players in the body’s milieu to fight off infections. It is a retrovirus, meanings its viral information in the form of RNA, which is transcribed by the enzyme reverse transcriptase into DNA when it infects a cell. Through specific steps, the viral genetic information is incorporated into the cell’s genome, or genetic code. From there it may remain latent, until it replicates new viral particles, and go on to infect and kill other cells, while the body attempts to control the spread. Initially the body is able to control the surge of viral replication, but ultimately the virus overcomes the body’s response. Usually over a period of years, it will deplete the number of T cells, and with it the ability of the body to fight off different types of infections. When the CD4 count hits below the magic number of 200 (or if the patient acquires specific AIDS defining “opportunistic infections”), the patient is diagnosed with AIDS.

The real problem with HIIV is not the virus itself per se, but more-so by the resulting immune dysfunction of the host. The crippling of the immune system leads to the acquisition of “opportunistic infections.” These are infections that are not commonly seen in immunocompetent patients, and ones that occur much more commonly in HIV patients. Common types of these infections include fungal infections (such as PCP pneumonia, histoplasmosis, thrush, toxomplasmosis), viruses (such as CMV, and Herpes Zoster, PML), and bacteria (Tuberculosis, cryptococcal meningitis, bacterial pneumonias). The virus itself can also cause other diseases, and cause damage to various organs, from somewhat unclear methods. These include neurological diseases and dementia, heart failure, bone marrow suppression, kidney failure, and certain cancers such as lymphoma. Many of these tend to occur late in the course of the disease. Other important problems associated with HIV are related to the medications and their toxic side effects. There is a broad spectrum of side effects towards many organ systems with the anti-viral regiments used, and one must always consider this as a contributing factor to an acute problem.

The virus can only be transmitted from person to person via blood products, sexual contact, or vertically--from mother to child during birth, or via breast feeding. The major modes of transmission between humans are sexual contact—particularly male to male homosexual contact, and injection drug use--through sharing of needles. Transmission via tears, sweat, or saliva has never been reported to occur in the absence of any blood contact. Blood products are routinely screened for viruses now, and the rate of transfusion related infection has been nearly eliminated.

What makes HIV difficult to control is its ability to mutate, which is related to the poor proofreading of the enzymes involved in constructing the virus from its genetic code. This causes the virus to change ever so slightly, but often enough. The drugs we have attack various parts of the HIV life cycle, however given the high mutation rate in the virus as it replicates, it can quickly create strands that will evade the medications’ recognition, and deem them ineffective in controlling the virus life cycle. This is why if patients do not take their HIV medications consistently, it will allow the virus to replicate, and give it more chances to mutate and brew resistant strains to the medications.

Beginnings

So where exactly did the virus come from? If you said "monkeys", you are sort of right. The first unofficially recorded human case of the virus is reported to be back in the 1950s in New York, and the first fully documented case did not occur until the early 1980s. However, suspected cases of the virus have been reported to be present in the human species as far back as the 1930's in Sub-Saharan Africa, where the virus likely originated.

It is known that primates such as the rhesus monkey carried a virus that attacked the immune system, which is known as the Simian Immunodeficiency Virus (SIV). Strains of SIV are closely related to HIV based on the similarity in its DNA architecture, and certain strains are almost identical. This is believed to be the origins of HIV. At some point, the virus crossed over species from primates to humans (zoonosis). The mode of transmission is not completely known, but it had to have been from close contact of with the blood and fluid of infected animals. It is known that hunters in Africa would closely handle infected animals that they would kill and eat. Blood to blood transmission where animal blood would come into contact with wounds and cuts from the slaying and butchering, and during the process of cooking and eating, are the most probable ways this occurred (and no, contrary to urband legends, they didn't have sex with the monkeys).

After the initial transmission from primates to humans, the virus subsequently spread rapidly among local populations, and pretty soon the world. Many theories exist for this spread. The initial propagation was most likely through heterosexual human contact within the African continent. The spreading of the virus outside of Africa was initially the result of the colonial rule at the time, and of visiting Europeans, coming from cities such as Paris and Spain into the African region. At the time, there was a large European interest in the African subcontinent for its sex industry. In addition to forced slave labor, they often would come to seek out cheap sex and to acquire sex slaves. These individuals would unknowingly acquire the virus from native Africans, and brought the virus back to their respective countries, from where it continued to spread sexually and vertically (from mother to child). This was soon followed by American tourists from both the East and West coasts, acquiring the virus from Africans, and probably by then from Europe as well, which in turn brought the disease for the first time back to the United States.

In the United States, there were two major areas for the virus to flourish. One was in New York City, where intravenous drug use was rampant at the time. The upswing of the heroin industry, and the common practice of sharing needles was the major player in New York's affliction. Buildings and houses in inner-city areas of New York would serve as places people would come to to purcahase drugs and do them together-- crack-houses for heroin. They would share needles with each other, oblivious that at some point in time, this unknown virus had surfaced among their population, spreading it from person to person, remaining silent and undetectable, as they indulged in their drug habits.

The second area in the U.S. which fostered the spread of HIV was in the San Francisco Bay area. Here however, it was mostly related to sexual transmission, particularly gay male to male sex. San Francisco fostered a large, open, homosexual population from the 1970s to the 1980s. During this time, the Bay Area would have many bathouses where gay men would come, meet, and have sex with other anonymous males. Somewhat analagous to the drug houses that would spread disease in NYC via intravenous drugs, the bathouses would spread the disease among the gay populations of the west coast through homosexual contact. Sex and drugs, from coast to coast. It had a head start of many years, and it took advantage of our human behavior.

Conclusions

We know a lot about HIV today, down to its specific genetic makeup, its life cycle, and how it builds resistance to our drugs. We have been successfully been able to create several types and classes of drugs to target HIV and its life cycle, and when used properly, can suppress the disease extremely well in many people. Using the appropriate milieu of medications in conjunction with one another, often referred to as HAART (highly active anti-retroviral therapy), can prolong the course of disease, limit the number of opportunistic infections, and improve survival. Some think it is starting to become a chronic disease that can be treated, but not cured. However, this may be true in certain patients and communities who are compliant and can afford the right medications, but given the populations it usually afflicts, this remains far from the truth.

Then reasons that the third world, primarly Africa, suffers so much more from the perils of this disease are simple: education, access, and money. These are our barriers for both prevention and treatment of disease. Despite what all of us may know, the fact that the virus is transmitted primarily through unprotected sexual contact is not something taught to many populations, therefore the virus continues to spread. In addition, pregnant women transmit the virus to their newborns every year—about 500,000 per year in Africa, whereas the right medication can virtually eliminate this transmission. For those that are chronically infected, medications remain too expensive and inaccessible. Although some larger cities are slowly improving their access to care and education, extending such public health efforts to remote villages remains a Herculean task.

HIV continues to be a worldwide killer, and a challenge for physicians and scientists across the globe. After years of intensive research, the emergence of new drugs and therapeutic guidelines, we continue to attain a better understanding of the disease and its management; however, we struggle to develop a vaccine or a cure. Despite good available treatment, we struggle with providing adequate access to health care and establishing preventative measures worldwide. Until the time arrives when we can overcome these feats, this worldwide epidemic will continue to pose a great challenge.

Image Courtesy Corbis