Gaborone, Botswana. 1. HAART has transformed HIV infection

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• HIV AND HIV MUTANTS
• E. Chigidi and E. Lungu
• University of Botswana
• Private Bag 0022
• Gaborone, Botswana

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• 1. HAART has transformed HIV infection into a
  chronic manageable disease.
  
• 2. However, Although many regimens lower plasma
  viral load to below the limit of detection in
  most patients, maintaining a durable response
  remains challenging because of
• (I) Adverse effects
• (II) Long term toxicity
• (III) Drug resistance

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• 4. Adverse effects Metabolic toxicity
  associated with Protease Inhibitor use have
  resulted in increasing use of regimens containing
  NNRTIs
• 5. Even NRTIs have also been associated with
  long term toxicity
  
• 6. Mutations of virus can occur before anti- HIV
  therapy is started

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• 7. Mutations can occur in two ways
• (a) Natural selection
• (b) Transmission of drug-resistant
  virus
  
• Natural selection
• (a) HIV makes mistakes during copying and
  produces variants
  
• (b) Some variants have mutations that allow
  the virus to partly or even full resist an
  
• anti-HIV drug

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• 9. Many HIV-positive people now take anti-HIV
  drugs.
  
• 10. Some have already developed resistance to one
  or more of these drugs
  
• 11. If they have unprotected sex with another
  individual they can pass on this strain.
  
• 12. The individual infected with this strain
  might have a problem controlling their viral
  load.

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• Is there evidence of HIV mutations
• 13. A study of 23 patients in Botswana on
• Either (a) DDI 3TC Nevirapine
• NRTI NRTI Nevirapine
• Or D4T 3TC Nevirapine
• NRTI NRTI Nevirapine
• 14. Of 15 patients who discontinued treatment
• Seven patients were found to possess the
  mutant virus K65R

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• Study by Gallant et el (2006) comparing two
  regimens involving 35 patients
  
• Regimen 1. TDF emtricitabine efavirenz
• NRTI NRTI NNRTI
• (12 Patients)
• Regimen 2. AZT 3TC efavirenz
• NRTI NRTI NNRTI
• (23 Patients)
• On Regimen 1 2 developed M184V/I mutations
• On Regimen 2. 7 developed M184V/I mutations

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• The mutant virus K65R was not detected in both
  groups
  
• However, exposure to NNRTI efavirenz resulted in
  the development of mutation K103N in 21 out of 35
  patients
  
• Other mutations were detected such as K101E,
  K103E, V108I/M V179D, Y188H, G190A/S/E, P225H,
  M230L

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• In western countries where choice for anti-HIV
  drugs is greater and financial constraints are
  not so acute, the rate of evolution of drug
  resistant strains has, to a large extent, been
  matched by the rate of development of new drugs.
• Sub-Sahara Africa is affected by several barriers
  namely, financial, organizational, physical and
  social.
  
• Drug resistant strains will cause high levels of
  transmitted HIV resistance and possibly lead to a
  reduction in the effectiveness of control efforts.

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• We investigate the following scenario
  Drug-resistant strains are less well transmitted
  than the wild-type strain. However, the drug
  resistant strain will evolve and its transmission
  characteristics will improve. Can this compound
  the current epidemic? How soon?
• We formulate a mathematical model in which we
  vary the probability of transmission and the
  proportions and the rate at which individuals
  start treatment in order to predict the spread
  of the disease.

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• Model diagram Model without treatment

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Model equations
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Model diagram Model with treatment
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Model equations incorporating treatment
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Endemic equilibrium point
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Model without treatment (left) and with treatment
(right)
for a constant population model
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Model without treatment (left) and with treatment
(right)
for a varying population model
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Model without treatment (left) and with treatment
(right)
for a constant population model
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Model without treatment (left) and with treatment
(right)
for a varying population model
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