hiv

1. Newer category of Anti-Hiv
drugs in clinical trial
By-
ARUP SAHA
M.Pharm,1st sem

2. Some HIV Facts
• HIV – the Human
Immunodeficiency
Virus is the retrovirus
that causes AIDS
• HIV belongs to the
retrovirus subfamily
lentivirus.
• HIV attaches to cells
with CD4 receptors
(T4 cells and
macrophages).

3. HIV Life Cycle1
Step 1: Attachment of virus at the CD4
receptor and chemokine co-
receptors CXCR4 or CCR5
Step 2: viral fusion and uncoating
Step 3: Reverse transcriptase makes a
single DNA copy of the viral RNA
and then makes another to form a
double stranded viral DNA
Step 4: Now the viral DNA transported
across the nucleus and Integration
of the viral DNA into cellular DNA by
the enzyme integrase
Step 5: Transcription and RNA processing
Step 6: Protein synthesis occurred and
new viral RNA and protein move to
the cell surface and a new immune
HIV forms
Step 7: Now the virion matured

4. Current classes of antiretroviral drugs
include :
Fusion or Entry
Inhibitors
Nucleoside/Nucleoti
de Reverse
Transcriptase
Inhibitors
Non-Nucleoside
Reverse
Transcriptase
Inhibitors
Protease Inhibitors
Integrase Inhibitors

5. Fusion or Entry Inhibitors
• It inhibit HIV from entering to the human cells.
• There are two types:
Fusion inhibitors
CCR5 inhibitors
CCR5 inhibitors won’t work in everyone and are
not often used for first-line treatment.

6. Fusion or Entry Inhibitors
 There is currently one
drug in the fusion
inhibitor class, called T-
20 (enfuvirtide,
Fuzeon).Enfuvirtide is the
first fusion inhibitor drug.
This is now only
prescribed in very
rare and specific
circumstances.
 Drug used for CCR5
inhibitors are Maraviroc,
Celsentri.

7. Nucleoside/Nucleotide Reverse Transcriptase
Inhibitors
• Nucleoside reverse
transcriptase inhibitors
(NRTIs) and nucleotide
reverse transcriptase
inhibitors (NtRTIs), which
target an HIV protein
called reverse transcriptase,
• This class of drugs forms the
‘backbone’ of a firstline HIV
treatment combination and is
usually
taken in a pill that combines a
number of drugs

8. Currently Available Nucleoside Analogs (NRTI’s)
• zidovudine/Retrovir
• didanosine/Videx
• zalcitabine/HIVID
• stavudine/Zerit
• lamivudine/Epivir
• abacavir/Ziagen
Zidovudine/Retrovir
didanosine/Videx

9. Non-Nucleoside Reverse Transcriptase
Inhibitors
• Non-Nucleoside Reverse
Transcriptase Inhibitors
(NNRTIs), started to be
approved in 1997.
• Like the Nucleoside Inhibitors,
NNRTIs (also known as non-
nucleosides) stop HIV from
replicating within cells by
inhibiting the reverse
transcriptase protein.
• Three NNRTI’s are currently
approved for clinical use in
combination therapy:
nevirapine, delavirdine, and
efavirenz
Efavirenz
Delavirdine

10. Protease inhibitors (PIs)
• During the reproduction cycle of HIV a specific
protease is needed to process polyproteins into
mature HIV components.
• If protease is missing noninfectious HIV is
produced.
• HIV protease inhibitors are specific to HIV
protease because it differs significantly from
human protease.
• The 6 PI’s currently approved for clinical use were
all designed by using structure-based drug design
methods4.

11. Protease inhibitor
• indinavir/Crixivan
• ritonavir/Norvirs
• aquinavir/Invirase,
Fortovase
• nelfinavir/Viracept
• amprenavir/Ageneras
• elopinavir/ritonavir,
Kaletra
Indinavir/Crixivan
Nelfinavir/Viracept

12. Integrase Inhibitors
• Integrase inhibitors,
which target a protein
in HIV called
integrase, and stop the
virus from
integrating into the
DNA of human cells.
 Drugs which are used
as anti integrase
inhibitors are
Raltegravir, Isentress
Raltegravir

13. Cabotegravir : It is an investigational new
drug under development for the
treatment of HIV infection.It is an
integrease inhibitor. This would make
possible suppression of HIV with dosing
as infrequently as once every three
months
Cenicriviroc:Cenicriviroc is an inhibitor
of CCR2 and CCR5 receptors allowing it
to function as an entry inhibitor which
prevents the virus from entering into a
human cell. Inhibition of CCR2 may have
an anti-inflammatory effect
Anti HIV drug in clinical trial

14. Doravirine : Doravirine is a non-
nucleoside reverse
transcriptase inhibitor for
use in the treatment of
HIV/AIDS under
development by Merck &
Co. This is now in clinical
phase III
Elvucitabine : It belongs to a class
of HIV drugs called
nucleoside reverse
transcriptase inhibitors
(NRTIs).Scientists are said
that elvucitabine may be
effective against hepatitis B
virus (HBV)Currently, it is in
Phase II clinical trials.

15. Fosdevirine : It is a Non-
nucleoside Reverse
Transcriptase Inhibitors
and developed by Idenix
Pharmaceuticals.Currently
it is in Phase of
Development II .
CENSAVUDINE : It is an
investigational new drug being
developed by Bristol Myers-
Squibb for the treatment of
HIV infection. Censavudine is a
nucleoside reverse
transcriptase inhibitor.

16. Doravirine : It is a non-nucleoside
reverse transcriptase
inhibitor under development
by Merck & Co. for use in the
treatment of
HIV/AIDS.Doravirine
appeared safe and generally
well-tolerated with most
adverse events being mild-
to-moderate.
Apricitabine : sometimes
abbreviated to ATC is an
experimental nucleoside
reverse transcriptase
inhibitor (NRTI) against HIV.
It is clinical phase III.

17. PRO 140 : It could be the first self-injectable HIV
antibody on the global market. PRO 140
belongs to a new class of HIV/AIDS
therapeutics -- viral-entry inhibitors -- that are
intended to protect healthy cells from viral
infection. it is developed by CYTODYN. If all
goes well CytoDyn could submit its NDA
(New Drug Application) for final approval in
November 2016 and it will marketed in 2017.
First self-injectable HIV antibody

18. REFERANCE
• An Introduction to Medicinal Chemistry by
Graham L. Patrick
• https://aidsinfo.nih.gov/clinical-trials
• https://Wikipedia .com