Abstract
Over thirty years after its identification, HIV and AIDS remains a somewhat elusive virus, particularly when it comes to its history as a human infectious agent, and resourcing a complete epidemiology of the disease. Part of the problem is that so many antiretroviral drugs have come out and have either been used or prescribed incorrectly. In addition, the virus, like many other reverse RNA transcriptase viruses, has a very high aptitude in terms of developing resistance to drugs at a very rapid rate. What further complicates matters is how quickly it has spread. It will probably never truly be known how many people have died from from this illness, nor will it ever be known how many people are infected with it at any given time, the WHO estimates that the number today is around 35 million. A patient zero will never be known, though there is a lot of speculation as to who brought it to the U.S. With so many mutations of the virus, research and development of new treatments are taking an exciting direction, a direction that has provided us with a decent vaccine, a prophylactic that is effective for days after contact, and the possibility of several emerging cures within the next few years.
Key Words: HIV, AIDS, Antiretroviral drugs, reverse RNA transcriptase, WHO, mutations.
History
The most pervasive type of HIV is HIV-1, Group B, Subgroup M, Clave H, with over hundreds (if not thousands) of Serotypes. The first case of HIV was described in 1981, but without proper surveillance, it went though several changes in its nomenclature. The main population impacted in the United States was and remains the homosexual population, and the initial accepted name for it was GRID, or Gay-Related Immune Disorder.The virus was attacking so rapidly after a few years, that the world's leading epidemiologists scrambled to describe the genetic patterns of the disease. Relatively shortly, a group of scientists who were sharing information on tests they were running were able o describe one serotype of the disease.
Thirty years later, a lot more is known about the history of the disease, though misconceptions of its beginnings still exist. We know the disease probably originated from chimpanzees in Southeast Cameroon (Sharp, P, 2010). At some point, people from this area made their way to Haiti (Thus making patient zero someone, or a group of people, who made their way from Haiti to other parts of the Americas), and the spread to the United States was really only a matter of time (Junquiera, 2011). Any other speculation is really just that, based on genetic evidence we now have.
For several years, as it was originally widely accepted by the general public that the only method of transmission was through sexual contact, and that someone must have had relations with one of those animals. This notion, along with many other silly ideas, spread around throughout the eighties', and led to many politicians refusing to fund its research,. Most Notably, this was the Reagan family.
The truth is probably far less beastialic. Bushmeat is a common food source throughout Central Africa. Walking through the bushes, people who are hunting often experience cuts, and in killing chimpanzees, there is a lot of blood as well. At some point in history, a crossover event, or genetic mutation that made the disease of SIV in other primates, made the jump to human blood infection possible.
Many think that this must have happened within the span of a few years before the disease was first being experienced. We now have evidence that this jump to human infectability most likely occurred in the very early 20th Century. This was discovered via genetic dating analysis using serotypes.
HIV is characterized as a specific lentovirus, that comes directly from the SIV line, via several chimpanzee serotypes. The SIV line is estimated to be anywhere from 4 to 30 million years old. SIV started out among humans as an extremely evolved set of "species" to begin with.
The disease, as we all now should know, does not just spread through homosexual sex. In fact, the United States seems to be one of the only areas where this is true. This makes the theory that patient zero in the US must have been an airline pilot only somewhat plausible. In Africa, it is spread through bush-meat consumption initially, than spread through heterosexual sex. The case is similar in South America. In other parts of the world the sex worker business has made its contribution to the number infected, as has intravenous drug use and children being born with it. To call it a "gay cancer" only is really a pretty odd correlation when it is caused by so many other things. It has since become one of the most lethal diseases in human history.
Symptoms of the Disease
The symptoms of HIV itself are not easy to recognize. There may be periods of fever initially after infection, maybe some weakness as the immune system is depleted, but the main thing that happens as the CD4 count is destroyed, is that people come down sick with opportunist infections and illnesses that are extremely painful, and usually easily defeated by the average human's innate immunity. This includes several cancers, the most notable of which is Sarcoma of the skin.
As HIV-1 progresses to AIDS, typically characterized by a CD4 count of under 200, an elevated viral load (many infectious disease doctors disagree on a number in terms of much virus needs to be present), and at least one life threatening event of illness. Note, by the time a person's CD4 count, the common cold will quickly become pneumonia or bronchitis, the stomach flu will become months of severe problems with digestive problems, and any elevated amount of carcinogens is likely to cause a spike in cancerous cells or tumors. A staph infection, especially of drug-resistant nature, is likely a death sentence, even today. Most people who die from the disease, as of 2015 (WHO), die from rare forms of Tuberculosis.
So, to summarize, as long as a person is able to stabilize their CD4 levels at around normal (800-1200), keeps a low viral load, and takes care to avoid areas where there could be a high risk of exposure to an illness, at least when their CD4 count begins to slough away, the disease itself is usually asymptomatic. This may sound wonderful, but in reality, it complicates the diagnosis of the disease. If people don't feel sick, they usually don't go to the doctor. This has highly complicated diagnosis of the illness, and has likely led it to become the tragic pandemic that it is.
Causes of the Disease
The causes of the disease will be separated from the epidemiology by discussing here the ways that the disease is transmitted, and when it was discovered that it could be spread that way. When it comes to the epidemiology and surveillance of HIV-1, it becomes quite a wild and complicated story. Even within the scope of this category, a lot more is known now than was before.
The number one cause of of HIV-1 transmission worldwide is heterosexual sexual contact, typically between a married man and woman. This surprises many Americans, so it bears a little explanation. In South America, and in particular, Africa and Southeast Asia, men hunt (sometimes women). They don't hunt with guns, and often without means so much as ineffective bows and arrows. They attack their prey much the same way one would expect a tiger to attack an antelope. There is usually a sharp object, such as a machete, used during the hunt, but the primary weapon is usually the human's own body. Through use of the machete, there is automatically a lot of blood contact by the time the human uses their body. If these men are already cut from running shoeless, or if the prey attacks back and happens to be infected with a form of SIV, The chance of its spread and quick adaptation to the human form of the disease (HIV) is quite likely, given the amount of blood that is involved. It was initially thought that this was an event that occurred around the time that HIV-1 was first described, but biogenetic dating methods have found that the rate of evolution of certain types of HIV-1 Subgroup B have estimated that this method of contact has probably been occurring since at least the 1920's.
Sexual contact between two men has been the largest cause for the disease's spread in more developed areas of the world. It has remained perpetually so, despite educational efforts, access to free condoms, and a genuine but fading fear of the disease. This is surprising, but may be indicative of just how quickly strains and substrains of the illness are able to adapt. This type of infection has been occurring, once again through seromutations, since the 1950's, and possibly earlier, Testing of all substrains has not yet occurred, so it is probable that this disease was spread via homosexual intercourse before the fifties.
Other ways of the diseases spread includes from mother to child, intravenous drug use (sharing needles), blood contact with a person who has the disease, even if that is through the simple act of kissing.
Populations most Affected in the United States
The homosexual population in the United States has been the most impacted, followed by intravenous drug users, children who are born with the disease, and the most quickly growing population, African American males who have bisexual tendencies. From a socioeconomic standpoint, and from a sociocultural standpoint, it is far less acceptable for black men in the United States to come out as gay or bisexual. It is an interesting paradox, because, generally speaking, the black population in America is overwhelming supportive of gay rights. Among black men, however, they face a scourge of bullying from their friends, and disownership from their families. As a result, these men will lead heterosexual lives in front of their communities, while going out and having sex, on what has been termed "the downlow." There is really no way to know how many people practice this, because it is so secretive. The only number epidemiologists can really go off of is how many men have tested positive, and have admitted to living this kind of lifestyle to exit counselors via anonymous surveillance. There are also a small number of people who have become infected via blood transfusions, though this number is nearing zero in the United State, as more careful practices are established when people donate blood.
Methods To Contain the Disease
No matter the part of the world, education about the disease is the first way to contain it. If people do not know that the disease exists, why would they do anything to try and stop its spread. This has been a fundamental concern in Southeastern Asia and Africa, where the stigma of the disease is so real, that people do not really know about it. People who are open about their status are deemed demonic or possessed, and as these people die, their families are given the same "diagnosis" by their neighbors and community. This cultural dynamic has basically halted any form of education about the disease within these communities.
In places where knowledge of the disease is more common, the key to containment is threefold. First, the infected need to use protection each and every time they have sex. The numbers, mentioned in the next section, speak for themselves. The simple act of putting on a condom in the United States seems to be a difficult task. Second, sexual partners need to be honest about their status with the person they are about to have sex with, and people need to understand that just because they are both infected does not mean to stop using protection. This is how superstrains and more virulent strains come to be. In order to be honest about one's status, they have to know what their status is. Third, people who are infected need to do their best to maintain an undetectable viral load. Recent research suggests that transmission of HIV from one person to another is close to impossible when the viral load is undetectable.
This is where a little more epidemiology can be looked at. Today, it is estimated by the WHO (2015-6) that there are just under 30 million people living with HIV. Since 1981, this is also the number of people who have died from the disease. This gives us a grand total of about 60 million people who have or had HIV/AIDS in the world. This obviously does not include the people who died not knowing they were infected, or people who have it now, and do not know they have it.
There is no way to characterize that number of those two subcategories other then to offer estimates well in the millions for both. This includes cases that have occurred since the major HIV-1B(M)-H serotype has been around. Though we know a lot, there are still several epidemiological questions that are left unanswered. As we grow closer to a cure, we may never really know all the answers, which will always make this an interesting field to go into.
In terms of the US,The Centers For Disease Control (CDC, 2016) came out with some fresh numbers. There are currently 1.2 million people in the United States living with the disease, though that includes the 1 in 8 people in the general public that do not know they have it. About 13,000 people died due to complications related to HIV last year, This a significant drop over ten years ago, when the deaths were almost equal to the common cold. This new number makes it still the third most lethal infectious disease in the country, first still being the common cold, and the rapidly proliferating MRSA (once known as Methicillin Resistant S. Aureus, now known as Medication Resistant because of how many antibiotics this bacteria has conquered). In a couple charts, the phylogeny of the disease is looked at, as well as some graphs that are relevant in an epidemiological context.
Graph 1. Phylogeny of SIV to HIV (CHS Pesrpsectives, Google Images, 2011)
Picture 1. Likely primates that contributed to development of HIV 1 and 2. (CHS Perspectives, Google Images, 2010)
Graph 2. Phylogeny of HIV 1B Clave H. (PLOS ONE, 2016)
The last graph is courtesy of PLOS One, and looks like something meaningless at first glance. It would have to be blown to the size of approximately 5000% to produce the intricacies of HIV-1B-Clave H. It represents approximately 48% of all cases worldwide, and virtually every American case. It also represents all the superstrains (which are visible), and all their substrains. This is the result of cross-resistance, which occurs for a variety of reasons, one of which will be explained in a couple sections.
The Public Health Cost of HIV-1
These numbers are grabbed from the Kaiser Foundation, and are from 2016. They only represent what the United States government allocates to HIV every year. Though it spends about 34 billion dollars globally, most of that money is retained in the United States. Of the 6.6 billion given globally, most of it goes towards testing, education, condoms, and basic treatments, now mostly given in the form of the triple combo drug released about 15 years ago by the copyrighted name of Atripla. It was the first medication available in the form of a once a day pill. Within the United States, he money is mostly devoted to treatment, housing, medicaid/medicare, education, and condoms, as well as to many subsidized organizations throughout the country, mostly through the form of the Ryan White Foundation. Money is also allocated to research, grants, and hospital mobilization. Private contributions are made through very wealthy philanthropists, mainly American, such as Bill Gates, whose contributions are comparable to what the U.S. government itself gives globally per year.
Treatments
There has recently been a gigantic boom in drug treatments, possible vaccines, and morning after pills, and several potential cures. The story of HIV treatment is a sad one though. Millions of people suffered for years before anything was available, and millions also died. AZT was finally approved, and did little to help. In fact, in many people, the symptoms only worsened before the drug. Quickly other drugs were developed and used in combination anti-retroviral therapy. Before long, mountains of pills had to be consumed by patients on a daily basis, a life many people compared to death. Usually these therapies were prescribed immediately upon diagnosis, to mixed results. There is no doubt that life was extended -- early public figures such as Magic Johnson and Greg Louganis have now lived since the beginning of combination anti-retroviral therapy -- but it has probably certainly helped that therapies have truly been on a boom since the turn of the century.
Atripla (TM), was the first combination therapy available in one pill a day. Doctors and experts really started to question when to begin these therapies. By the mid 2000's, it was largely agreed that therapies should not begin until the CD4 count and viral load reach certain levels (400-500, 100,000-1,000,000 respectively) (Cohen, et al, 2008). This generally occurs after about three to four years after infection. This is because the risk of human error in taking these medications the wrong way can render them useless. Cases when early combination therapy should be used is when a person already has a chronic illness, or if they are pregnant. There are a number of therapies out now that are not combination therapies, and can be taken as little as once a week in trials. There is a vaccine that is about 70% effective available in parts of the world outside of the US (for now). That is a considerable percentage. PReP, if taken within a certain window of sexual contact, is very effective in blocking the virus. A working cure in Germany has been discovered, though it is not a practical treatment, as it requires as blood marrow transplant from a person who is immune to HIV (that is to say, they lack the CCR5 receptor site on their T cells, one of two needed for HIV to attach itself to those immune cells). There are several different pathways to cures, many of which entail microgenetic manipulation, transference or removal of genes that code for miRNA that initially make contact with the virus as soon as it has invaded a cell. It is an exciting time to be a medical biotechnologist.
Future Efforts
We seem to clearly be on the right path in terms of research. We need to work harder in certain populations to reduce the stigma of a positive HIV diagnosis. This is throughout the world, but it is also right in America's backyard. In gay communities, there are two major categories that need to be worked on, bullies within these communities, and "bug-chasers" a weird fixation with trying to have sex to catch the illness.
Conclusion
HIV 1 has a much more detailed history than most people realize. Evolution, after all, is not something that happens overnight. It happens over generations and generations, over millions of years, whether the organism is a human, with billions of genes, only a third of which we fully understand, or a small little strand of RNA that comprises HIV. We have made great strides in the treatment of HIV, but ultimately, more needs to be done. We are so close to the end of this horrendous illness. Education is the best way to contain this disease, trials need to be concluded to see if we have, in fact, found a cure. Stigmas need to be removed, and hopefully soon, this will be a disease people look back on the way they do the Spanish Flu, something horrific that has happened in the past, something that can be researched as we brave the next epidemic around the corner.
References
CDC. (2016). "HIV in the United States: At A Glance." Centers for Disease Control Retrieved from http://www.cdc.gov/hiv/statistics/overview
/ataglance.html
Cohen, et. al. (2008). "The spread, treatment, and prevention of HIV-1:
evolution of a global pandemic." JCI. Accessed from
https://www.jci.org/articles/view/34706
Junquiera, D. et al. (2011). "Reviewing the History of HIV-1: Spread of Subtype
B in the Americas." PLOS ONE. Retrieved from http://journals.plos.org/
plosone/article?id=10.1371/journal.pone.0027489
Kaiser Family Foundation (2016). "U.S. Federal Funding for HIV/AIDS: Trends
Over Time." kff.org Accessed From http://kff.org/global-health-
policy/fact-sheet/u-s-federal-funding-for-hivaids-trends-over-time/
Sharp, P. and Hahn, B. (2010). "The evolution of HIV-1 and the origin of AIDS."
The Royal Society. Retrieved from http://rstb.royalsocietypublishing.org
/content/365/1552/2487
WHO. (2016). "HIV/AIDS." World Health Organization. Retrieved from
http://www.who.int/features/qa/71/en/
Graphs and Pictures
Graph 1. Phylogeny of SIV to HIV. (CSH Perspectives, Google Images, 2014)
Picture 1. Likely primates that contributed to development of HIV 1 and
2. (CSH Perspectives, Google Images, 2010)
Graph 2. Phylogeny of HIV 1B Clave H. (PLOS ONE, 2016)
