Transcript HIV-AIDS part-2

Highly Active Antiretroviral
Therapy (HAART)
Cocktail Therapy
Examples of anti-retroviral drugs
• Cocktail Drug Mixtures
– Protease inhibitors
– Non-nucleoside RT Inhibitors (NNRTIs)
– Nuleoside/nucleotide RT inhibitors (NRTIs)
– * Fusion Inhibitors
– Integrase Inhibitors
*Fuzeon
Fusion Inhibitors block
• Co-receptors on host cell
or
• Gp120/gp 41 on viral particle
Acquired Immunodeficiency
Disease
Symptoms of AIDS
• Decrease T cell count
• Rapid weight loss
• Recurring fever and dry
cough
• Profound fatigue
• Swollen lymph glands
Symptoms of AIDS
• Persistent diarrhea
• Unusual blemishes on the tongue, mouth, or
throat
• pneumonia
• memory loss, depression
Acquired Immunodeficiency Syndrome
Opportunistic Diseases and cancer
• pneumonia
• Kaposi’s Sarcoma
Kaposi’s Sarcoma
Transmission of HIV
Transmission of HIV
• Biological fluids
– Blood
– Sexual transmission (Semen)
– Breast milk
– Transplant tissues
Non-transmitting sources of HIV
• Tears
• Saliva
• Mosquito or insects
• Swimming pool
• Food handling
Prevention
• Condoms
• Clean needles
• Treatment of pregnant mother with anti-viral
drugs
• Blood screening
• Abstinence
For Your Information and Files
Acquired Immunodeficiency Syndrome
• Normal CD4+ count
• Normal CD4+ (%)
• 500-1600/mm3
• 20-40%
• <350/mm3 begin anti-viral treatment
• AIDS
• <14% serious immune damage
Table 1. For Your personal Information: not for lecture.
Antiretroviral Agents
Agent
Type
Dose
Major Toxicities
AZT
NRTI
300 mg bid
nausea, headache,
low blood counts
ddI
NRTI
125-200 mg bid or
250-400 mg qd
(tablet form)
diarrhea, pancreatitis,
peripheral neuropathy
ddC
NRTI
0.750 mg tid
diarrhea,
peripheral neuropathy
d4T
NRTI
30-40 mg bid
abnormal liver function tests,
peripheral neuropathy
3TC
NRTI
150 mg bid
minor
abacavir
NRTI
300 mg bid
hypersensitivity reaction
tenofovir
NRTI
(nucleotid
e)
300 mg qd
nausea, diarrhea, vomiting,
flatulence
AZT/3TC
(Combivir)
NRTI
one pill bid
(300 mg AZT/150 mg 3TC)
see above
AZT/3TC/a
bacavir
(Trizivir)
NRTI
one pill bid
(300 mg AZT/150 mg 3TC/
300 mg abacavir)
see above
nevirapine
NNRTI
200 mg bid
rash
delavirdin
e
NNRTI
400 mg tid
rash
efavirenz
NNRTI
600 mg qhs
rash, dizziness, impaired
concentration, insomnia,
abnormal dreams
saquinavir PI
(Fortovase
)
1200 mg tid
diarrhea
ritonavir
PI
600 mg bid
nausea/vomiting,
drug interactions
indinavir
PI
800 mg tid
kidney stones
nelfinavir
PI
750 mg tid
or 1250 mg bid
diarrhea
amprenavi
r
PI
1200 mg bid
nausea/vomiting,
diarrhea, rash
three capsules bid
(133.3 mg lopinavir/33.3 mg
diarrhea, nausea, weakness,
headache
lopinavir/ri PI
tonavir
Experimental drugs are italicized, and approved drugs are in regular, non-italicized type)
Brand Name
Fuzeon™
Generic Name
Abbreviation
Experimental Code
Pharmaceutical Company
enfuvirtide
ENF
T-20
Trimeris and Hoffmann-La Roche
BMS-488043
Bristol-Myers Squibb
GSK-873,140
GlaxoSmithKline
PRO-542
Progenics Pharmaceuticals
SCH-D
Schering-Plough Corporation
TNX-355
Tanox and Biogen Idec
UK-427,857
Pfizer
Interesting links on HIV
• http://www.niaid.nih.gov/factsheets/aidsstat.
htm
– Links to global and US HIV/AIDS statistics
• http://www.avert.org/pregnanc.htm
– Links to HIV and pregnancy as well as numerous other
links including statistics on global epidemic; HIV/AIDS
quizzes and treatment.
• http://www.cdc.gov/hiv/pubs/facts/transmission.ht
m
– Links to CDC and a comprehensive fact sheet on HIV transmission
Experimental drugs are italicized, and approved drugs are in regular, non-italicized type)
Brand NameGeneric NameAbbreviationExperimental Code Pharmaceutical Company
Fuzeon™enfuvirtideENFT-20Trimeris and Hoffmann-La Roche
BMS-488043Bristol-Myers
Squibb
GSK-873,140GlaxoSmithKline
PRO-542Progenics Pharmaceuticals
SCHDSchering-Plough Corporation
TNX-355Tanox and Biogen Idec
UK-427,857Pfizer
What
are
Entry
Inhibitors
(including
Fusion
Inhibitors)?
Entry inhibitors work by preventing HIV from entering healthy T-cells in the body. They work
differently than many of the approved anti-HIV drugs – the protease inhibitors (PIs), the
nucleoside reverse transcriptase inhibitors (NRTIs), and the non-nucleoside reverse
transcriptase inhibitors (NNRTIs) – which are active against HIV after it has infected a T-cell.
Entry inhibitors work by attaching themselves to proteins on the surface of T-cells or proteins on
the surface of HIV. In order for HIV to bind to T-cells, the proteins on HIV's outer coat must bind
to the proteins on the surface of T-cells. Entry inhibitors prevent this from happening. Some entry
inhibitors target the gp120 or gp41 proteins on HIV's surface. Some entry inhibitors target the
CD4 protein or the CCR5 or CXCR4 receptors on a T-cell's surface. If entry inhibitors are
successful in blocking these proteins, HIV is unable to bind to the surface of T-cells and gain
entry
into
the
cells.
Only one entry inhibitor has been approved by the U.S. Food and Drug Administration (FDA):
Fuzeon™ (T-20). This drug targets the gp41 protein on HIV's surface. Some experimental drugs
target proteins on T-cells: BMS-488043 targets the gp120 protein, PRO-542 and TNX-355 target
the CD4 protein, and SCH-D, GSK-873,140 and UK-427,857 target the CCR5 protein.
HIV-positive people who have become resistant to PIs, NRTIs, and NNRTIs will likely benefit
from the entry inhibitors because they are a different class of drugs. This is good news for HIVpositive people who have tried and failed many of the currently approved anti-HIV medications.
To learn more on how HIV infects a T-cell and begins to create more viruses, and where each
class of anti-HIV drugs blocks this process, click on the following lesson link:
The
HIV
Life
Cycle
(and
the
targets
of
each
class
of
anti-HIV
drugs)