HIV AND HIV MUTANTS
E. Chigidi and E. Lungu
University of Botswana
Private Bag 0022
Gaborone, Botswana
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
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 antiHIV therapy is started
7. Mutations can occur in two ways
(a) Natural selection
(b) Transmission of drug-resistant virus
8. 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
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.
• 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
• 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
• 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
• 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.
• We investigate the following scenario: Drugresistant 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.
Model diagram: Model without treatment
Model equations
Model diagram: Model with treatment
Model equations incorporating treatment
Endemic equilibrium point
Model without treatment (left) and with treatment (right)
for a constant population model
Model without treatment (left) and with treatment (right)
for a varying population model
Model without treatment (left) and with treatment (right)
for a constant population model
Model without treatment (left) and with treatment (right)
for a varying population model