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AIDS TREATMENT HAART

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HIGHLY ACTIVE ANTI RETROVIRUS THERAPY – PowerPoint PPT presentation

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Title: AIDS TREATMENT HAART


1
HAART
2

Highly Active Anti Retrovirus Therapy
(HAART) Acquired Immuno Deficiency Syndrome
(AIDS)- ragic fact AIDS was recognized as a
distinct disease entity as recent the 1980 , in
this brief period it has become one of most
devastating afflictions in the history of
mankind. AIDS is caused by infection with the
human immune deficiency virus (HIV).it is
estimated that there are more than 42 million
HIV-infected individuals in the world , more than
21 million deaths attributable to this disease,
and more than 3 million death annually. The
infection continues to spread, especially in
Africa and Asia and Europe , more than 30 of the
population has been infected with HIV , how
researches can be help in HIV treatment and
vaccination strategies . The presentation of this
paper concludes with the brief discussion of the
current status of the HAART - The current
treatment of AIDS is aimed at controlling
replication of HIV and the infectious
complications of the disease . cocktail of drugs
that block the activity of the viral reverse
transcriptase , protease and integrase enzymes
are now being administrated early in the course
of infection .
T
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  • Administration of Vorinostat Disrupts HIV-1
  • Latency in Patients on ART
  • The 19 Conference on Retrovirus and
    Opportunistic Infections (CROI)
  • 5-8. March. 2012
  • Objectives
  • Identify molecular mechanisms underlying
    proviral latency and HIV persistence despite anti
    retroviral therapy.
  • Discover drug candidates and therapeutic
    approaches capable of depleting persistence
    infection.
  • Establish informative animal system to study HIV
    persistence and test therapeutic strategies .
  • Study basis of viral persistence in human

American Academy Of HIV Medicine
3
4

Abstract 157LB
Research leading to cure HIV/AIDS
Resting CD4 cells infection it is extremely
despite ART and is primary reservoir of
persistence HIV infection. Histone Deacetylases(
HDACs) contribute to the maintenance of latency
of HIV integrated into the Genome of CD4
T-cells. The class 1 HDAC is HDAC 1,2 and 3 are
the primary enzymes that drive this effect at the
HIV LTR in CD4 T-cell.
4
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Vorinostat is a novel anticancer agent that
inhibits class I and II histone deacetylases.1 It
exerts anticancer effects by direct inhibition of
histone deacetylases, modulating both histone and
nonhistone proteins that regulate various cell
signaling pathways. Vorinostat induces apoptosis,
inhibits proliferation, enhances anticancer
immunity, and interrupts angiogenesis in a
variety of preclinical cancer models. Vorinostat
is approved by the US Food and Drug
Administration (FDA) for the treatment
of refractory cutaneous T-cell lymphoma. It
is administered at a dose of 400 mg orally daily.
5
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Vorinostat Suberoylanilide Hydroxamic Acid (SAHA)
  • Potent oral HDAC inhibitor.
  • Licensed for treatment of cutaneous lymphoma
    .
  • Selective inhibitor of HDAC 1,2,3 .
  • Induced expression of latent HIV from the
    resting CD4 cells of HIV positive patient ex
    vivo.
  • Single dose proof-of-concept
  • Can VOR disrupt latency of CD4 T-cells in
    vivo????

6
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Step 1
Harvest resting CD4 T cells, establish
baseline resting cells HIV RNA , and demonstrate
that change is detectable after a physiological
exposure to VOR
Step 2
Single 400 VOR Dose 12 hr VOR PK and celluar
biomarkers of HDACi effectTotal cell histone
acetylation and histone acetylation of human p21
gene
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Step 3
Mean 4.8 fold induction(range1.5-10 fold)
No AE gtGrade 1 All increases
significant (Plt0.01) No
AE due to VOR
Single copy plasma HIV RNA -
8
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Conclusion
A single dose of VOR induces expression of
full-length HIV RNA within latency infected
resting CD4 T-cell. This is first direct
measurement of disruption of latent HIV infection
in vivo. A change in single copy viremia
couldn't be observe after a single dose of
VOR. Real-time measures of resting CD4T-cells
Associated HIV RNA could prove useful in the
evaluation of the eradication strategies. The
optimal dosing schedules of VOR and it is ability
to deplete of latent infection, remains to be
established. About the Author David
Margolis. Professor of medicine,microbiology,immun
ology University of North Carolina at Chapel
Hill
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