Biomedical Engineering Reference
In-Depth Information
100
10
75
7.5
50
5.0
2.5
25
0
NNVC 4
NNVC 5 HAART Vehicle
NNVC 4
NNVC 5
Vehicle
HAART
FIGURE 7.6
Effect.of.NNVC.treatment.on.implant.thymocyte.depletion.and.viral.load.in.implant.at.30.days.postinfection..
Left:.Thymocyte.depletion..The.percentage.of.CD4
+
CD8
+
.thymocytes.in.the.implant.are.expressed.as.the.mean.
±.SEM,.n.=.3..Right:.Implant.viral.load..Results.are.the.mean.±.SEM.of.the.qPCR.at.three.different.dilutions.from.
three.implants.per.group.
Implants.in.the.HAART.and.NNVC.4.and.5.treatment.groups.had.80%-85%.CD4
+
.CD8
+
.
cells,.while.the.vehicle.control.groups.had.approximately.30%.CD4
+
CD8
+
.thymocytes.
As.shown.in.Figure 7.7,.the.control,.vehicle-treated.mice.died.at.30.days.postinfection,.
while.the.mice.treated.with.the.HAART.cocktail.survived.until.42.days.postinfection,.a.
40%. increase. in.survival.. The.groups. treated. with. nanoviricides.had.increased. survival.
compared.to.the.control.vehicle-treated.mice..Of.signiicance,.the.NNVC.4.and.5.groups.
had.survival.that.was.comparable.or.slightly.superior.to.that.of.mice.treated.with.HAART,.
44.3.and.42.2.days,.respectively..There.was.also.a.signiicant.body.weight.loss.in.the.vehi-
cle. treatment. group.. Body. weight. loss. in. the. HAART. treatment. group. was. reduced. by.
more.than.40%..Consistent.with.the.survival.results,.treatment.with.NNVC.4.and.5.had.
a.similar.beneicial.effect.on.body.weight.loss,.approximately.50%.less.than.the.vehicle-
treated.group.
In. summary,. treatment. of. SCID-hu. mice. with. NNVC. 4. and. 5. following. HIV-1. Ba-L.
infection.of.Thy/Liv.implants.resulted.in.signiicantly.reduced.viral.load.and.signiicantly.
improved.double-positive.CD4
+
.CD8
+
.thymocyte.proportion..These.effects.appear.to.have.
resulted. in. improved. survival. and. reduced. body. weight. loss.. Importantly,. comparison.
with. mice. treated. with. the. HAART. cocktail. for. the. duration. of. the. study. revealed. that.
the.NNVC.4.and.5.antiviral.agents.were.comparable.or.slightly.superior.to.HAART.treat-
ment.for.all.parameters.evaluated..It.is.important.to.note.that.NNVC.4.and.5.were.single.
administrations.only.at.24,.48,.and.72.hours.postinfection,.while.the.HAART.cocktail.was.
administered. daily. for. the. duration. of. the. study.. The. NNVC. total. drug. load. was. only.
150.mg/kg,.as.opposed.to.a.total.HAART.drug.load.of.4,200.mg/kg;.thus,.equivalent.effects.
were.observed.with.NNVC.drug.candidates.at.~1/20th.of.the.HAART.drug.load..It.would.
be. important. to. determine. if. extended. nanoviricide. administration. shows. signiicantly.
TABLE 7.3
Viral.Particles.in.Aspirated.Implant.Lymphocytes
Treatment
No.
of
Viral
Particles
per
EM
Field
Vehicle
240
NNVC.4
11
NNVC.5
11
HAART
47
