HIV drug resistance mutations // Drug Repurposing

HIV drug resistance mutations

3.1 Recap of previous section

The set the stage:

  • We have a genetic organism – in this case a virus (HIV).
  • After infecting a cell, the virus can replicates many times. HIV produces more than 100 million new virions every 1–2 days.
  • But HIV has no proofreading mechanism. It makes at least one mistake (mutation) just by chance in each replication cycle.
  • Someone who is not on treatment is likely to have every possible single mutation the HIV genome. We don’t have one virus but a pool or soup of thousands of slightly different types of HIV.

3.2 Introduction to section 3

Section 3 looks at how HIV mutations behave when HIV drugs are around (i.e. in the presence of drugs).

3.3 Wild-type virus and drug pressure

In someone not on treatment, mutations that develop that can affect how a drug works are made at random.

When no drug resistant mutations are present, this HIV is called ‘wild type’.

Mutations generally make HIV less fit at replicating. Wild type HIV is therefore stronger and fitter that drug resistant HIV.

When not on treatment, drug resistant HIV has no advantage over the wild type. It is less fit and so wild type continues to be dominant. The muation may still be in the pool of viruses but it will stay a minority.

  • The main strain will be the fittest virus (ie wild type when not on treatment).
  • A mutation that stops a drug working is called ‘a mutation associated with drug resistance’ or, more commonly, ‘a drug resistant mutation’.
  • As long as you are not taking the drug associated with this resistance, this mutation will have no relative advantage over wild type virus.

Now think about how the pool of viruses will change if you start taking this drug.

  • The drug will be able to kill most of the viruses in the pool. However, it will not be active against the virus that is resistant to the drug.
  • The drug resistant virus will continue to replicate. This resistant virus now has an advantage over the other viruses. It is relatively more fit.
  • Slowly, the drug resistant HIV will become dominant in the pool.
  • In the presence of the drug, further mutations can develop and make the resistance even stronger.

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A new, untreatable strain of the sexually transmitted disease gonorrhea has been discovered in Japan, according to an international team of infectious disease experts. The strain, named H041, is resistant to all known forms of antibiotics.
The finding was presented Monday with extensive laboratory evidence at a conference in Quebec City, Canada — and it comes just three days after the Centers for Disease Control and Prevention (CDC) warned that U.S. gonorrhea samples had being showing new signs of drug resistance as well. The CDC said that analysis of bacteria samples taken from 2000 to 2010 showed that the gonorrhea bug was becoming less and less susceptible to the frontline drugs, cephalosporins, as the years went by

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THURSDAY, May 1, 2014 (HealthDay News) -- Antibiotic-resistant bacteria are now found worldwide, a situation that could have serious public health consequences, the World Health Organization warns in a new report.
The WHO's first global survey of antibiotic resistance revealed high rates of drug-resistant E. coli bacteria. In some countries, treatment for E. coli is ineffective in more than half of patients. The agency also discovered alarming rates of resistance in other bacteria, including gonorrhea, the Associated Press reported. Without urgent action to counter the threat, "the world is headed for a post-antibiotic era in which common infections and minor injuries which have been treatable for decades can once again kill," Keiji Fukuda, MD, one of the agency's assistant director-generals, said in a news release, according to the AP

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Patients to be screened for extensively drug-resistant TB at CMCH from July 1  — The Hindu
All the multi drug-resistant tuberculosis (MDR TB) patients coming for treatment at the Coimbatore Medical College Hospital (CMCH) will be diagnosed immediately for extensively drug-resistant tuberculosis (XDR-TB) from July 1.

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Gonorrhea drifting toward cephalosporin resistance.(INFECTIOUS DISEASES)(Report): An article from: Internal Medicine News
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Penicillin-resistant gonorrhea: January 1977 through December 1979, 622 citations (Literature search)
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