HIV; The Origins and Search for a Cure.

When the Aids Pandemic began in the 1980’s, it overwhelmed the public consciousness. While scientists struggled to understand the cause and origins of the disease, fear of its unknown and mysterious nature generated prejudice against its victims. Since then, researchers have gained an astounding amount of knowledge about the HIV/AIDS virus and have even made progress towards a cure. Yet in the face of advancing understanding of the disease it is ironic that the general public is less educated than they were in the past. There is a general belief that AIDS/HIV affects gay men, minorities, and sub-Saharan populations but is not a threat beyond those communities. The truth is that people of every race, gender, age, and socio-economic status are at risk. While millions of people are infected with the virus, one in six people in the US alone is not aware of their infection.

HIV/AIDS is still a reality. It is the world’s most critical modern pandemic, and more people are infected every day. It is more important than ever that we continue our awareness and support for a cure. For the first time in history, a cure is actually within reach. This is brief story of how a deadly virus evolves, how communities exist, and how scientists have searched for a cure.

After decades of research, ignorance is rampant. The ignorance has become embedded in our culture. HIV/AIDS has become a 'pop virus'. Everybody knows the name, but the disease remains remote from everyday reality for most of us.

To fully understand the picture, we need to look at the history of the HIV virus and the mechanisms by which it attacks the human body. That means understanding why some people are immune and how some have been cured. It is crucial that we all know that HIV/AIDS can infect anyone, that awareness and prevention are vital, and that research and development are moving towards finding a possible cure for this illness which still plagues the entire world.

Understanding how HIV/AIDS developed and infects people leads us to the interesting fact that people who are HIV resistant are also linked to survivors of the 13th century Black Death.

Both diseases are fatal to their hosts, and both originated in animals humans interacted with. A disease crosses over from animals to humans through the process of ‘zoonosis.’ Most of the world’s deadly plagues, flues and other pandemic diseases have been attributed to ‘zoonosis’.

Zoonosis begins with an animal population, infected with a pathogen, living in close proximity to a human population. The animal and human populations have to interact enough for repeated exposure, giving the pathogen the opportunity to mutate over the course of many exposures (100,000+) to the point that it can actually 'take hold' in the human body and successfully spread in the population.

Such ‘exposures’ must involve blood-to-blood contact. The wild ape populationin the Congo was a natural carrier of SIV (Simian Immunodeficiency virus, which is very similar to HIV). Humans living in close proximity to wild ape populations regularly hunted and butchered them for food which is a bloody process. A small cut on the hand during the process and the hunter has blood-to-blood contact with the infected ape.

It’s possible to date the beginnings of a virus by looking at its gene mutations and structure. In this way, scientists found that the HIV virus actually dates back as far as 1908. This blows away all assumptions that HIV is a disease of gay men that developed in the 1980s.

We know that HIV has been infecting humans since the beginning of the 20th century. However, no one knew what it was at the time. The HIV virus causes a host of symptoms ranging from pneumonia to cancer, and deaths were simply attributed to something else or to unknown causes. The first truly documented cases of HIV were in 1959 and 1960 when two people in the Congo died from it.

At the time, their deaths were considered so mysterious that doctors preserved their samples for later testing. Thirty years later In the 1990s, those samples were finally tested and found to have HIV.

HIV is a retro virus. It actually writes itself into the host's DNA and becomes a part of the host's genome. In order to do this, it works like a lock and key; breaking into the host’s cells. Once HIV is in the body, it locks onto receptors on the human cell, and opens the cell and inserts itself. Once inside, it carries out reverse transcription using RNA and copies itself with the host DNA. Once it does this, it releases many particles of this replicated DNA mix and sends them back out into the body, to hijack more human cells. Its ultimate destination is the T-cell, located in the immune system. Once the virus reaches the T-cells, it is able to destroy the immune system.

Once the host’s infected T-cell count hits a critical tipping point, full blown AIDS develops. Some people can live for a very long time with HIV, as long as they are able to keep their T-cell count in check so that the virus does not develop into full blown AIDS. This can be done with anti-retroviral drugs.

Some people are not immune to AIDS, but are what we call 'elite controllers'. This means that they can have HIV, but their body does an exceptional job at regulating it and they may not even need medication to live a long healthy life.

One of the best known AIDS patients, Magic Johnson, has had a dedicated regime of anti-retrovirals over many years. It is also thought that he may fall into this category of elite controllers. While Johnson has not been “cured,” his T-cell count may be depressed due to his natural biology or (most likely) medication. The count is so low that if he takes a standard HIV test, his results are negative. That is not uncommon. It does not mean that he does not have the virus. He has done exceptionally well with medication. If he were to go off the medication, he would eventually develop AIDS.

There are many people who have had HIV for twenty or thirty years, and are still alive and very healthy. This is not the case for everyone, but with modern anti-retrovirals many patients are able to keep their t-cell count down for decades.

Who are these 'elite controllers'? Some people really do have a genetic resistance or even immunity to HIV. There is a genetic mutation called CCR5 Delta 32. If you have this mutation from one parent, you may very well become an 'elite controller'. This means that you can get HIV, but your body can handle it very well naturally and you may not even need medication to live a healthy life with the virus. If you have 2 copies of this gene, there is a good chance you are actually immune to HIV.

How does CCR5 delta 32 work? Where does it come from? Who does it effect?

People who have the CCR5 Delta 32 mutation lack the protein structure on their cells that HIV needs to unlock the cell for entry. The virus cannot infect the living host organism, because it can't get in.

Researchers have found that, if your ancestors survived the Black Death, you have a higher chance of having the genetic material that makes you HIV resistant. The mystery is that while the black death was caused by a bacteria, HIV is a virus. How does immunity to one relate to immunity against the other?

Evolutionary biologists have traced a significant increase in CCR5 delta 32 mutation in the human population back to the year 1300 - only in places where the plague had been prevalent. This is also the time when the black death was entering Europe. Like HIV, some people were actually immune to the black death, and some people survived it. The black death enters the human cell using the same key system that HIV would use. Researchers believe that the protein coating mutation that CCR5 delta 32 makes, prevented the black death bacteria from entering the system in the same way that it prevents HIV from entering the system.

It turns out that in order to have survived the plague, you needed to have at least one copy of the CCR5 delta 32 mutation. In order to be totally immune so that you didn’t contract the disease at all, you needed two copies of it from both parents. Obviously, people who were able to survive the plague, were more likely to be able to produce offspring and their offspring (carrying their CCR5 delta 32 mutation that they inherited from their parents) were more likely to survive future waves of the black death and have their own offspring.

Today, we are able to do genetic traces for small villages where many families have been living for centuries. In these isolated and consistent populations scientists were able to identify people who are alive today, and who had ancestors who were known to survive the plague. When this was first studied in the town of Ewly, England, it was discovered that 14% of the people alive today and who had ancestors who survived the plague also carried the mutation.

The mutation is only found in populations of European descent.

Indian, Asian, African and Native American populations do not carry this mutation. It is estimated that 10-20% of Europe's ancestors carry the mutation today, and that less than 1% actually carry the double mutation from both parents that bestows total immunity. The mutation is most common in Scandinavian and Northern European populations.

There are, however, some strains of HIV that can infect the system by other avenues, so having a CCR5 Delta 32 mutation may protect some people to an extent, but not all. So, having the CCR5 Delta 32 mutation may make you an elite controller, or it may give you a better chance of handling the virus in the body, but actual immunity is very rare.

Are people actually getting cured? There has been a lot of media attention and many of us are confused as to its truth. There are a few different stories.

Here are the basic facts:

There are a couple of people who have been functionally cured of HIV. This means that the virus count is so low in their body, that it is nearly undetectable. Some of these people are on medication and some are not. This is usually achieved by an early therapy of high anti retroviral dosage. Magic Johnson is a case in point.

Two babies born with HIV in the last three years were treated aggressively with anti retrovirals immediately after birth. The early interruption in the virus has enabled them to stay virtually virus free. One baby is still on medication. The other is not. She was on anti retrovirals for the first 18 months of her life, and she has been off of ART (anti retroviral treatment) for two years. Currently, It seems that she may have actually been cured, since the HIV virus can no longer be detected in her system. However, it is still not clear if this is a sterilizing cure, in which case she is free entirely of the virus, or a functional one, in which case the HIV virus remains in her system but in quantities too low to detect and impact her health. We will probably not have a clear answer about either of these babies until they are a bit older and have been off of ART for a few more years.

There are also numerous adults who have been functionally cured due to early treatment. 14 patients in France known as the Visconti Patients, were treated with high doses of anti-retro virals (ART) within 10 weeks of infection for a matter of months. These patients have now been off of ART for 7-10 years and naturally keep the virus at such low levels in their bodies, that it is barely detectable. This early treatment leads to a functional cure. Keep in mind that it is rare that someone discovers their infection so early on and that many will be infected for years before they discover that they are infected. So, while this story is promising, its practical implications may be limited.

At this point in time, functional cures using ART are more realistic than sterilizing cures. This is because researchers have not been able to replicate a sterilizing cure in an adult. It has only happened once. However, we are seeing more and more cases of effective functional cures, and this appears to be the most realistic path scientists will have luck with in the near future.

There is only one known case of an actual AIDS cure. In 2008, Timothy Brown received a stem cell transplant (bone marrow) from a donor who had the CCR5 delta 32 mutation. His body actually adapted this mutation with time, and to this day he is off of ART with no traceable amount of the virus in his system. This was a major breakthrough. Unfortunately, researchers have not been able to replicate it to date. They did attempt the procedure with two men in Boston and in both cases it was not successful. A bone marrow transplant is a risky procedure and the above patients received it because of a cancer they had developed due to AIDS. Bone marrow transplants are thus not a suitable option for every HIV patient. While the procedure has only been effective once and it is not a practical option for every HIV patient, it still shows something very promising; it is possible to clear HIV with the CCR5 delta 32 mutation. More research is needed in this area and, it is possible that in the future we will have a clearer understanding of how to use this to our advantage in a possible AIDS cure.

It is crucial that we continue supporting awareness and prevention as well as research and development to find treatments and possibly a cure for this illness. The medical community and policy makers have to work harder to ensure that people are educated about HIV/AIDS prevention and dangers. Researchers must continue to receive the attention and funding that they need to progress further in finding a cure and treatments. People need to understand that this is a treatable disease and that a cure is a real possibility that may be developed soon. We have come so far already, and with continued support and awareness the future could have a positive outcome for millions of victims.

Sources:

HIV Black death Link:

http://www.livescience.com/9983-immune-hiv.html

http://www.sciencedaily.com/releases/2005/03/050325234239.htm

http://www.hivplusmag.com/case-studies/research-breakthroughs/2012/09/07/anyone-immune-hiv

Secrets of the DEAD PBS Documentary:

http://www.youtube.com/watch?v=BRrolqaU7fA

http://en.wikipedia.org/wiki/Eyam

why the vaccination is difficult:

http://au.ibtimes.com/articles/497274/20130807/top-10-factors-why-hiv-vaccine-cure.htm#.U1vW1GSSyEA

http://aids.gov/hiv-aids-basics/prevention/prevention-research/vaccines/

http://www.sciencedaily.com/releases/2012/09/120909150350.htm

replication

http://aids.gov/hiv-aids-basics/just-diagnosed-with-hiv-aids/hiv-in-your-body/hiv-lifecycle/

t cell picture:

http://www.google.de/imgres?imgurl=http%3A%2F%2Findianapublicmedia.org%2Fnews%2Ffiles%2F2013%2F06%2FHIV-NIH-NIAID.jpg&imgrefurl=http%3A%2F%2Findianapublicmedia.org%2Fnews%2Flilly-donates-10-million-dollars-bioscience-institute-51623%2F&h=445&w=640&tbnid=z-A9THLqye1IqM%3A&zoom=1&docid=RX8RBqKb2-osCM&ei=MjdeU6GWEcvMtAaM_IHYBA&tbm=isch&iact=rc&uact=3&dur=618&page=1&start=0&ndsp=17&ved=0CHMQrQMwCQ

SIV

http://en.wikipedia.org/wiki/Simian_immunodeficiency_virus

SIV vaccine

http://www.bbc.com/news/science-environment-24051860

drc 60

http://www.google.de/imgres?imgurl=http%3A%2F%2Forigin.arstechnica.com%2Fjournals%2Fscience.media%2FCongo.jpg&imgrefurl=http%3A%2F%2Farstechnica.com%2Fscience%2F2008%2F10%2Ftracing-the-origin-of-hiv-1%2F&h=242&w=186&tbnid=RRgIUTYTxqa8_M%3A&zoom=1&docid=GFfmy-dekg-KzM&ei=Pj5eU6_ELIe0tAbPkYGQBA&tbm=isch&iact=rc&uact=3&dur=367&page=1&start=0&ndsp=21&ved=0CF8QrQMwAw

geographical spread

http://www.google.de/imgres?imgurl=http%3A%2F%2Fimg.medscape.com%2Farticle%2F760%2F844%2F760844-fig4.jpg&imgrefurl=http%3A%2F%2Fwww.medscape.com%2Fviewarticle%2F760844_4&h=637&w=762&tbnid=LrEqP7O9kfQnxM%3A&zoom=1&docid=b0zcuiqKSSzRUM&ei=QD1eU7vTEIfbsgbg0YHIAw&tbm=isch&iact=rc&uact=3&dur=385&page=2&start=20&ndsp=25&ved=0CKMBEK0DMBc

Dendric cell

http://www.google.de/imgres?imgurl=http%3A%2F%2Fupload.wikimedia.org%2Fwikipedia%2Fcommons%2Ff%2Ffa%2FDendritic_cell_revealed.jpg&imgrefurl=http%3A%2F%2Fen.wikipedia.org%2Fwiki%2FDendritic_cell&h=2250&w=3000&tbnid=U4E1EhPCj__7rM%3A&zoom=1&docid=CVRTmPoucQfQ5M&ei=AUNeU6SqO4mVtQb52IHoBA&tbm=isch&iact=rc&uact=3&dur=473&page=1&start=0&ndsp=17&ved=0CGEQrQMwAw

when did siv jump to humans and become HIV?

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2669881/

The day they discovered AIDS

http://www.msnbc.com/msnbc/the-day-they-discovered-the-aids-virus

how did the zoonosis begin in africa?

Sharp, P. M.; Bailes, E.; Chaudhuri, R. R.; Rodenburg, C. M.; Santiago, M. O.; Hahn, B. H. (2001). "The origins of acquired immune deficiency syndrome viruses: where and when?". Philosophical Transactions of the Royal Society B: Biological Sciences 356 (1410): 867–76.doi:10.1098/rstb.2001.0863. PMC 1088480. PMID 11405934.

Chitnis, Amit; Rawls, Diana; Moore, Jim (2000). "Origin of HIV Type 1 in Colonial French Equatorial Africa?". AIDS Research and Human Retroviruses 16

Merfield FG (1957) Gorillas were my Neighbours. London: The Company Book Club.

Jump up

^ Coquery-Vidrovitch C (1998). "The Upper-Sangha in the Time of the Concession Companies". Yale F & ES Bulletin 102: 72–84

German Cameroon Picture

http://www.google.de/imgres?imgurl=http%3A%2F%2Fupload.wikimedia.org%2Fwikipedia%2Fcommons%2Fb%2Fbb%2FAfrican_Pigmies_CNE-v1-p58-B.jpg&imgrefurl=http%3A%2F%2Fen.wikipedia.org%2Fwiki%2FScramble_for_Africa&h=2112&w=1382&tbnid=9ou-co5p-3A84M%3A&zoom=1&docid=4l33pKTIUf3hzM&ei=VF1eU5fUKoPYtAamn4H4BA&tbm=isch&iact=rc&uact=3&dur=558&page=1&start=0&ndsp=23&ved=0CH4QrQMwCw

Smallpox virus

http://www.google.de/imgres?imgurl=http%3A%2F%2Fwww.bbc.co.uk%2Fdrama%2Fcontent%2Fimages%2F2006%2F11%2F24%2Fsmallpox_396x222.jpg&imgrefurl=http%3A%2F%2Fwww.bbc.co.uk%2Fdrama%2Fsmallpox2002%2F&h=222&w=396&tbnid=yuL07-5WcU-gFM%3A&zoom=1&docid=ryr_XokoUvqKpM&ei=2F9eU47IFojUsgap6oDYDA&tbm=isch&iact=rc&uact=3&dur=916&page=1&start=0&ndsp=18&ved=0CGMQrQMwAg

Binding and Fusion

http://www.google.de/imgres?imgurl=http%3A%2F%2Fwww.mcld.co.uk%2Fhiv%2Fimages%2FbindingAndFusion.gif&imgrefurl=http%3A%2F%2Fwww.mcld.co.uk%2Fhiv%2F%3Fq%3Dbinding&h=142&w=454&tbnid=oWqVJ1TW4j6DpM%3A&zoom=1&docid=DiUMOri1Z9XcfM&ei=imReU76QDorMtAaL64GoCw&tbm=isch&iact=rc&uact=3&dur=4147&page=1&start=0&ndsp=17&ved=0CGoQrQMwBg

transcription

http://gallus.reactome.org/figures/HIV1_transcription_reg.jpg

HIV life cycle

http://aids.gov/hiv-aids-basics/just-diagnosed-with-hiv-aids/hiv-in-your-body/hiv-lifecycle/

Reverse transcription

PDB 1HMV; Rodgers DW, Gamblin SJ, Harris BA, Ray S, Culp JS, Hellmig B, Woolf DJ, Debouck C, Harrison SC (February 1995). "The structure of unliganded reverse transcriptase from the human immunodeficiency virus type 1". Proc. Natl. Acad. Sci. U.S.A. 92 (4): 1222–6. doi:10.1073/pnas.92.4.1222. PMC 42671. PMID 7532306.

HIV infection picture

http://www.ipmglobal.org/why-microbicides/how-microbicides-work

HIV AIDS DATA TODAY

http://aids.gov/federal-resources/around-the-world/global-aids-overview/

HIV origins and primate photos

http://en.wikipedia.org/wiki/HIV

is AIDS curable?

http://hivinsite.ucsf.edu/InSite?page=md-expert-deeks-pillai

Berlin and Boston patients

http://www.iol.co.za/scitech/science/news/relapse-of-cured-hiv-patients-1.1628153#.U1-PWWSSyEA

http://defeathiv.org/berlin/

http://www.nejm.org/doi/full/10.1056/NEJMoa0802905