Morgan BellDevelopments in HIV treatments (LINK)
June 1st 2008 15:07
HIV is a virus that mostly infects cells in the immune system.
A cell will often make new proteins in order to stay alive and to reproduce itself. In order for viruses to reproduce, they must hi-jack and infect a cell so they can use it to make new viruses. Viruses hide their own DNA in the DNA of the cell, and then, when the cell tries to make new proteins, it accidentally makes new viruses as well.
DNA is like the "blueprint" for building living cells. RNA is like the construction boss. Enzymes are like the workers of a cell. They build new proteins, transport materials around the cell, and carry out other important cellular functions. Cells use RNA to tell enzymes how to build a specific part of a cell. To make a new protein, enzymes will copy a specific part of the DNA into a piece of RNA. This RNA is then used by other enzymes to build a new protein or enzyme.
Although HIV infects a variety of cells, its main target is the T4-lymphocyte (also called the "T-helper cell"), a kind of white blood cell that has lots of CD4 receptors. The T4-cell is responsible for warning your immune system that there are invaders in the system. HIV searches for cells that have CD4 surface receptors, because this particular protein enables the virus to bind to the cell. Once HIV binds to a cell, it hides HIV DNA inside the cell's DNA: this turns the cell into a sort of HIV factory
Treatments currently exist to block HIV during its various stages of development
STAGE 1: BINDING
[blocked by entry inhibitors]
HIV has proteins on its outer envelope that are strongly attracted to the CD4 surface receptor on the outside of the T4-cell. When HIV binds to a CD4 surface receptor, it activates other proteins on the cell's surface, allowing the HIV envelope to fuse to the outside of the cell.
STAGE 2: REVERSE TRANSCRIPTION
[blocked by Nucleoside Reverse Transcriptase Inhibitors (NRTIs), and Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)]
After the binding process, the viral capsid (the inside of the virus which contains the RNA and important enzymes) is released into the host cell. In order for the virus to infect the cell, a process called "reverse transcription" makes a DNA copy of the virus's RNA. A viral enzyme called reverse transcriptase makes a DNA copy of the RNA. This new DNA is called "proviral DNA."
STAGE 3: INTEGRATION
[blocked by “integrase inhibitors”]
The HIV DNA is then carried to the cell's nucleus (center), where the cell's DNA is kept. Then, another viral enzyme called integrase hides the proviral DNA into the cell's DNA. Then, when the cell tries to make new proteins, it can accidentally make new HIVs.
STAGE 4: TRANSCRIPTION
[blocked by “antisense antivirals” or Transcription Inhibitors (TIs)]
Once HIV's genetic material is inside the cell's nucleus, it directs the cell to produce new HIV. The strands of viral DNA in the nucleus separate, and special enzymes create a complementary strand of genetic material called “messenger RNA” or mRNA (instructions for making new HIV).
STAGE 5: TRANSLATION
The mRNA carries instructions for making new viral proteins from the nucleus to a kind of workshop in the cell. Each section of the mRNA corresponds to a protein building block for making a part of HIV. As each mRNA strand is processed, a corresponding string of proteins is made. This process continues until the mRNA strand has been transformed or "translated" into new viral proteins needed to make a new virus.
STAGE 6: VIRAL ASSEMBLY AND MATURATION
[blocked by Protease Inhibitors (PIs) and Maturation Inhibitors]
New viral particles are assembled, then they bud off the host cell, and create a new virus. The maturation stage involves the processing of viral proteins and is the final step in the process which leads to the virus to become infectious. With viral assembly and maturation completed, the virus is able to infect new cells. Each infected cell can produce a lot of new viruses.
Developments in NTRIs (from STAGE 2)
NRTIs, sometimes called "nucleoside analogues" or "nukes," contain faulty versions of the building blocks (nucleotides) used by reverse transcriptase to convert RNA to DNA. When reverse transcriptase uses these faulty building blocks, the new DNA cannot be built correctly. In turn, HIV's genetic material cannot be incorporated into the healthy genetic material of the cell and prevents the cell from producing new virus. An NRTI prevents HIV from entering the nucleus of healthy T-cells. This prevents the cells from producing new virus and decreases the amount of virus in the body.
Brand name NRTIs that are currently approved include Atripla, Combivir, Emtriva, Epivir, Epzicom, Retrovir, Trizivir, Truvada, Videx & Videx EC, Viread, Zerit, Ziagen and are available from pharmaceutical companies Bristol-Myers Squibb, Gilead Sciences, and GlaxoSmithKline
The generic names of these drugs are efavirenz, tenofovir, emtricitabine, zidovudine, lamivudine, abacavir, didanosine, disoproxil, fumarate, and stavudine.
Racivir (Pharmasset), amdoxovir (RFS Pharma), apricitabine (Avexa Limited), and elvucitabine (Achillion Pharmaceuticals) are all experimental drugs which are currently undergoing trials.
Developments in Apricitabine (an NTRI)
Apricitabine is currently being developed by an Australian pharmaceutical company Avexa Limited. The drug was first developed by BioChem Pharma, it was then sold the Shire Pharmaceuticals who then sold the rights to develop the drug to Avexa. Apricitabine has not yet been evaluated or approved by the U.S. Food and Drug Administration.
Apricitabine's chemical structure is similar to that of approved drugs Epivir (lamivudine) and Emtriva (emtricitabine). A study has determined that Epivir can decrease the amount of apricitabine inside cells, meaning that apricitabine cannot be combined with Epivir or Emtriva.
Recently clinical trials of apricitabine by Avexa showed CD4 cell counts doubled compared with approved drug lamivudine. Evidence has shown switching from lamivudine to apricitabine decreases the viral load of the patients. At 48 weeks more than 90 percent of patients had HIV levels below detectable levels compared to 80 percent at 24 weeks
Avexa said the demonstrated ability of apricitabine to withstand selection of HIV resistance, even in patients who have already failed other drugs, differentiated it from some of the other HIV drugs in clinical use. No apricitabine resistance has been identified after 48 weeks of therapy.
CLICKHERE for details of clinical trial on Biotech Daily
A cell will often make new proteins in order to stay alive and to reproduce itself. In order for viruses to reproduce, they must hi-jack and infect a cell so they can use it to make new viruses. Viruses hide their own DNA in the DNA of the cell, and then, when the cell tries to make new proteins, it accidentally makes new viruses as well.
DNA is like the "blueprint" for building living cells. RNA is like the construction boss. Enzymes are like the workers of a cell. They build new proteins, transport materials around the cell, and carry out other important cellular functions. Cells use RNA to tell enzymes how to build a specific part of a cell. To make a new protein, enzymes will copy a specific part of the DNA into a piece of RNA. This RNA is then used by other enzymes to build a new protein or enzyme.
Although HIV infects a variety of cells, its main target is the T4-lymphocyte (also called the "T-helper cell"), a kind of white blood cell that has lots of CD4 receptors. The T4-cell is responsible for warning your immune system that there are invaders in the system. HIV searches for cells that have CD4 surface receptors, because this particular protein enables the virus to bind to the cell. Once HIV binds to a cell, it hides HIV DNA inside the cell's DNA: this turns the cell into a sort of HIV factory
Treatments currently exist to block HIV during its various stages of development
STAGE 1: BINDING
[blocked by entry inhibitors]
HIV has proteins on its outer envelope that are strongly attracted to the CD4 surface receptor on the outside of the T4-cell. When HIV binds to a CD4 surface receptor, it activates other proteins on the cell's surface, allowing the HIV envelope to fuse to the outside of the cell.
STAGE 2: REVERSE TRANSCRIPTION
[blocked by Nucleoside Reverse Transcriptase Inhibitors (NRTIs), and Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)]
After the binding process, the viral capsid (the inside of the virus which contains the RNA and important enzymes) is released into the host cell. In order for the virus to infect the cell, a process called "reverse transcription" makes a DNA copy of the virus's RNA. A viral enzyme called reverse transcriptase makes a DNA copy of the RNA. This new DNA is called "proviral DNA."
STAGE 3: INTEGRATION
[blocked by “integrase inhibitors”]
The HIV DNA is then carried to the cell's nucleus (center), where the cell's DNA is kept. Then, another viral enzyme called integrase hides the proviral DNA into the cell's DNA. Then, when the cell tries to make new proteins, it can accidentally make new HIVs.
STAGE 4: TRANSCRIPTION
[blocked by “antisense antivirals” or Transcription Inhibitors (TIs)]
Once HIV's genetic material is inside the cell's nucleus, it directs the cell to produce new HIV. The strands of viral DNA in the nucleus separate, and special enzymes create a complementary strand of genetic material called “messenger RNA” or mRNA (instructions for making new HIV).
STAGE 5: TRANSLATION
The mRNA carries instructions for making new viral proteins from the nucleus to a kind of workshop in the cell. Each section of the mRNA corresponds to a protein building block for making a part of HIV. As each mRNA strand is processed, a corresponding string of proteins is made. This process continues until the mRNA strand has been transformed or "translated" into new viral proteins needed to make a new virus.
STAGE 6: VIRAL ASSEMBLY AND MATURATION
[blocked by Protease Inhibitors (PIs) and Maturation Inhibitors]
New viral particles are assembled, then they bud off the host cell, and create a new virus. The maturation stage involves the processing of viral proteins and is the final step in the process which leads to the virus to become infectious. With viral assembly and maturation completed, the virus is able to infect new cells. Each infected cell can produce a lot of new viruses.
Developments in NTRIs (from STAGE 2)
NRTIs, sometimes called "nucleoside analogues" or "nukes," contain faulty versions of the building blocks (nucleotides) used by reverse transcriptase to convert RNA to DNA. When reverse transcriptase uses these faulty building blocks, the new DNA cannot be built correctly. In turn, HIV's genetic material cannot be incorporated into the healthy genetic material of the cell and prevents the cell from producing new virus. An NRTI prevents HIV from entering the nucleus of healthy T-cells. This prevents the cells from producing new virus and decreases the amount of virus in the body.
Brand name NRTIs that are currently approved include Atripla, Combivir, Emtriva, Epivir, Epzicom, Retrovir, Trizivir, Truvada, Videx & Videx EC, Viread, Zerit, Ziagen and are available from pharmaceutical companies Bristol-Myers Squibb, Gilead Sciences, and GlaxoSmithKline
The generic names of these drugs are efavirenz, tenofovir, emtricitabine, zidovudine, lamivudine, abacavir, didanosine, disoproxil, fumarate, and stavudine.
Racivir (Pharmasset), amdoxovir (RFS Pharma), apricitabine (Avexa Limited), and elvucitabine (Achillion Pharmaceuticals) are all experimental drugs which are currently undergoing trials.
Developments in Apricitabine (an NTRI)
Apricitabine is currently being developed by an Australian pharmaceutical company Avexa Limited. The drug was first developed by BioChem Pharma, it was then sold the Shire Pharmaceuticals who then sold the rights to develop the drug to Avexa. Apricitabine has not yet been evaluated or approved by the U.S. Food and Drug Administration.
Apricitabine's chemical structure is similar to that of approved drugs Epivir (lamivudine) and Emtriva (emtricitabine). A study has determined that Epivir can decrease the amount of apricitabine inside cells, meaning that apricitabine cannot be combined with Epivir or Emtriva.
Recently clinical trials of apricitabine by Avexa showed CD4 cell counts doubled compared with approved drug lamivudine. Evidence has shown switching from lamivudine to apricitabine decreases the viral load of the patients. At 48 weeks more than 90 percent of patients had HIV levels below detectable levels compared to 80 percent at 24 weeks
Avexa said the demonstrated ability of apricitabine to withstand selection of HIV resistance, even in patients who have already failed other drugs, differentiated it from some of the other HIV drugs in clinical use. No apricitabine resistance has been identified after 48 weeks of therapy.
CLICKHERE for details of clinical trial on Biotech Daily
| 154 |
| Vote |
Add To: 
Subscribe to this blog
Comment by S.L. Bradish
Comment by Morgan Bell
Deep Pencil
Current Business News
Movie Train
Artist Quirk
yes thankfully its not the death sentence it once was
im sorry to hear of the death of your relatives, it is a sad and terrible disease
screening blood for transfusions is another area of science that has improved remarkably in recent years
USE CONDOMS
DONT SHARE NEEDLES
and if you dont follow those two pieces of advice and exhibit flu-like symptoms see a doctor for treatment immediately
there is a PEP treatment you can take in the first 72 hours that everyone should know about also Really Long Link
Comment by RubySoho
Music Zone
Thought Zone
But it is actually illegal to deliberately attempt to spread the virus and people have been prosecuted for doing so.
Comment by Morgan Bell
Deep Pencil
Current Business News
Movie Train
Artist Quirk
i hope one day we have an immunisation, its a shame the problem was ignored for so long but research is coming along in leaps and bounds now
Comment by RubySoho
Music Zone
Thought Zone
Meh, at least something got them moving.
Comment by Louie
Climate Forum
Climate Red
randomthoughts
Phil's Wellness Tips
It is heartbreaking how many orphans there are in third world countries because of it, not to mention the children with aids and the staggering numbers of people suffering from the disease.
Comment by Morgan Bell
Deep Pencil
Current Business News
Movie Train
Artist Quirk
yeah when a white politicians teenage daughter gets it thats when the most funds come pouring in, but better late than never . . . its actually used to be referred to as the "gay cancer" and people thought it was some kind of a holy punishment for homosexuality (maybe some people still think that)
hi Louie,
i sometimes find it hard to fathom exactly how rampant HIV is in africa now, its almost like biological genocide where a whole race will be completely wiped out . . . and when paired with malnutrition and other diseases HIV is so much more deadly because the body has reduced immune
kudos to Elizabeth Taylor and other celebrities and scientists who have dedicated their lives to wiping this disease out
Comment by Cheryl J
Funny Videos
Rhythmatism
Zentertainment
Budget Centsability
Almost all of us have been touched in one way or another by this awful disease. I'm sure nearly everyone knows someone or at least a friend of a friend who has contracted it.
I just hope the greed of the pharmaceutical companies doesn't prevent these drugs from being distributed in poorer nations. They have blocked the making of low-cost substitutes before citing patent infringement yet they will not willingly provide low-cost or free meds in developing nations even though they could easily afford to. That is the truly sickening thing.
What a well written informative piece. Well done Morgan.
Comment by Morgan Bell
Deep Pencil
Current Business News
Movie Train
Artist Quirk
thanks for your comment
yes it would be my hope too that these drugs are distributed to whoever needs them regardless of their wealth . . . whether the pharmaceutical companies, or governments or charities subsidise them, just as long as it gets to the needy
Comment by Anonymous
Comment by Morgan Bell
Deep Pencil
Current Business News
Movie Train
Artist Quirk
thanks for the comment
yeah i would hate to think of anyone restricting access to medications in order to increase profits
Comment by postmoderncritic
Postmodern Critic
Daily Inspirations
Relativity Watch
Padsoc
Now if only I can get it through my head that I need to use condoms... I'm such a hypocrite because I totally advocate them... for everyone else. And then I freak out afterwards until I get tested.
Comment by Morgan Bell
Deep Pencil
Current Business News
Movie Train
Artist Quirk
dont make me shake my finger at you and cluck my tongue to produce the "tut tut" noise!
i am so impressed with the scientists of the world and their work in making this disease manageable . . . hopefully it will be erradicated one day!
Comment by postmoderncritic
Postmodern Critic
Daily Inspirations
Relativity Watch
Padsoc
Yes, I really hope we find a cure someday...
Comment by Morgan Bell
Deep Pencil
Current Business News
Movie Train
Artist Quirk