HIV causes AIDS by infecting and destroying helper T cells of the immune system. It is transmitted through bodily fluids and can be prevented by safe sex practices and not sharing drug needles. While there is no cure for AIDS, treatment aims to suppress HIV replication with antiretroviral drugs and manage opportunistic infections. Highly active antiretroviral therapy (HAART) uses a combination of different classes of antiretroviral drugs including nucleoside/nucleotide reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, fusion inhibitors, CCR5 receptor antagonists, and integrase inhibitors. Long term adherence to HAART can effectively suppress HIV and prolong the lives of

1. ACQUIRED IMMUNO
DEFICIENCY
SYNDROME (AIDS)
C H A I T H R A . B
1 S T M P H A R M
P H A R M A C O L O G Y
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2. INTRODUCTION
AIDS stands for ACQUIRED IMMUNO DEFICIENCY
SYNDROME .
It is a disease caused by the retrovirus HUMAN
IMMUNO DEFICIENCY VIRUS (HIV) and
characterized by immunosuppression that leads to
opportunistic infections and neurologic manifestations.
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3. ETIOLOGY
AIDS is caused by HIV, belongs to family of RNA viruses
known as retro viruses.They differ from other RNA viruses
as they must replicate through a DNA intermediate.
Two genetically different but related forms of HIV
called HIV-1 and HIV-2.HIV-1 is most common type in
USA, Europe and central Africa.HIV-2 in west Africa and
India.
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4. STRUCTURE OF HIV
Similar to most retro viruses, the HIV-1 virus is spherical and contains
cone shaped core surrounded by lipid envelop derived from the host cell
membrane.The HIV matrix proteins(consisting of the p17 protein),
lie between the envelope and core.
The virus core contains:
1) The major capsid protein P24.
2) Nucleo capsid protein P7/P9.
3) Two copies of genomic RNA.
4) Three viral enzymes;
a) Protease
b)Reverse transcriptase
c) Integrase.
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5. 5

6. P24 is the most readily detected viral antigen and is the
target for antibodies that are used for diagnosis of HIV
infection.
The viral core is surrounded by a matrix protein
called P17, which lies underneath the viral envelop .
The viral envelop consist of 2 viral glycoprotein gp120
and gp41, which are critical for HIV infection of cells.
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7. PATHOGENESIS OF HIV INFECTION
OR AIDS
HIV can infect many tissues. There are 2 major targets
of HIV infection :
1) The immune system.
2) Central nervous system.
HIV possesses the enzyme reverse transcriptase and
consist of lipid bilayer membrane surrounding the
capsid.
It’s surface glycoprotein molecule has strong affinity
for CD4 receptor protein found in helper –T cells.
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8. HIV enters the body and attaches to CD4 receptors
and co-receptors such as CCR-5 or CXCR-4 and
membrane fusion also occurs.
After penetrating into the host cell, virus sheds
its outer coat and release its genetic material and 3
replication enzymes. They are
Integrase
Reverse transcriptase
Protease.
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9. Using reverse transcriptase enzyme, the viral RNA is
converted into DNA. The viral DNA is then integrated
into the host genome in the cell nucleus. When
undergoes transcription and translation, it enables the
production of new viral protein.
New virus particles are then assembled and matures
into infectious virions under the influence of protease
enzyme.
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10. TRANSMISSION OF HIV
1) Unprotected intercourse :HIV can be found in
semen and cervical secretions.
2) parenteral transmission : Through contaminated
blood exposure, i.e. shared drug injection needles .
3)child birth : Through blood, amniotic fluid and
vaginal fluids.
4)contaminated blood and blood product: Receipt
of blood products, organ transplantation
5) breast feeding : breast milk
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11. SIGNS AND SYMPTOMS OF AIDS
Flu like symptoms,
Lack of energy,
Frequent fever and sweating,
Persistent skin rashes,
Short term memory loss,
Difficult or painful swallowing,
Cough or shortness of breath.
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12. DRUG TREATMENT
The drug treatment of HIV disease can be classified as :
1)Management of opportunistic infections.
2)Antiretroviral therapy.
3)Symptom control.
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13. MANAGEMENT OF OPPORTUNISTIC INFECTIONS
Some of the most common AIDS opportunistic infections are :
Meningitis
Encephalitis
Pneumonia and Tuberculosis
Chronic diarrhoea
Kaposi's sarcoma and non Hodgkin lymphoma.
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14. The general principles for management of opportunistic
infections include prospective immunologic monitoring,
primary prophylactic treatment and secondary
prophylaxis.
The treatment of many opportunistic complications of
HIV includes high dose therapy followed by
maintenance or secondary prophylaxis using lower
doses.
Primary prophylaxis may be offered to those who are
deemed to be at high risk of developing a particular
opportunistic infection.
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15. Example: Pneumonia Prophylaxis
Approximately 15-30% of HIV infected people develop
pneumonia caused by opportunistic fungus Pneumocystis
carinii. Treatment of pneumonia with agents such as
Cotrimoxazole (Trimethoprim+sulphamethoxazole) is
associated with 60-100% response rate.
Example:Meningitis
Amphotericin B is effective for treatment of cryptococcal
meningitis, because of its lower rate of early death and
disease progression.
Patients with meningitis should receive amphotericin B in an
i.v. dose of at least 0.5 mg/kg/day for minimum of 2 weeks.
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16. ANTIRETROVIRAL THERAPY
The goal of antiretroviral therapy of HIV related diseases are :
 Arrest of replication of HIV in vivo.
 Reconstitution of immunologic system damaged by the retrovirus.
A combination of drugs is used in AIDS to improve prognosis known
as “HAART” i.e. highly active antiretroviral therapy. HAART
regimen includes 2 NRTI with either NNTRTI or PIs.
Using a HAART regimen suppresses HIV replication and plasma
HIV RNA levels are greatly reduced and prolongs patients survival.
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17. CLASSIFICATION OF ANTIRETROVIRAL THERAPY
A)Nucleoside and Nucleotide Reverse
Transcriptase inhibitors (NRTIs)
E.g. : Zidovudine, Stavudine,
Lamivudine, Abacavir, Tenofovir.
B) Non-nucleoside Reverse transcriptase
inhibitors (NNRTIs) :
Eg : Nevirapine, Delavirdine , Etravirine.
C) Protease inhibitors :
Eg : Saquinavir , Indinavir, Ritonavir,
Amprenavir, Darunavir
D) Entry inhibitors: Eg : Enfuvirtide, maraviroc
E)Integrase inhibitors : Eg: Raltegravir
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18. 1. NUCLEOSIDE AND NUCLEOTIDE REVERSE
TRANSCRIPTASE INHIBITORS(NRTIS)
Eg: Zidovudine (AZT),Stavudine,Abacavir,Lamivudine.
It is the first drug to be used in the treatment of HIV infection.
Mechanism of action: Zidovudine
Zidovudine -triphosphate
Binds reverse transcriptase(RNA-dependent DNA polymerase)
Incorporate into viral DNA
Premature chain termination 18

19. ADVERSE EFFECTS
Bone marrow suppression, myelosuppression, anemia,
headache, anorexia, myalgia, fatigue, insomnia,
myopathy and neurotoxicity.
Uses
 AZT is the drug of choice in AIDS and
decreases opportunistic infections
 Weight gain
 It decreases disease progression
 During pregnancy.
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20. DRUG INTERACTIONS OF NRT INHIBITORS
a) Combination with other Myelosuppressants.
b) Combination with Stavudine decreases the
efficacy.
c) Combination with zalcitabine and didanosine
cause overlapping toxicity.
d) Combination of zalcitabine and lamivudine may
antagonize each other.
e) Alcohol increases plasma level of abacavir.
DOSE: Zidovudine:-200 mg bid.
Stavudine:-20-40 mg bid.
Abacavir:-300 mg bid.
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21. 2. NON-NUCLEOSIDE REVERSE TRANSCRIPTASE
INHIBITORS(NNRTIS)
Eg: Nevirapine , Delavirdine , Etravirine
Mechanism of action:
similar to NRTIs. But are not converted to
Triphosphate derivatives.
NNTRTIs are effective only against HIV-1.
Adverse effects
GI disturbances, allergic reactions such as skin
rashes, nausia, headache, sedation, fatigue, diarrhea,
abdominal pain and drowsiness.
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22. USES
Treatment of HIV-1 infections
Used in labour and in new born to prevent
transmission of HIV.
Drug interactions
Failure of oral contraceptives.
Delavirdine is microsomal enzyme inhibitor.it
also increases plasma level of PI’s.
DOSE :
Nevirapine :-200 mg/kg – onset of action.
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23. 3. PROTEASE INHIBITORS (PI'S)
Eg :Saquinavir ,Indinavir, Darunavir, Amprenavir.
Mechanism of action
HIV protease activity is essential for the activation of viral
enzyme and HIV replication. And also for the production of
mature virion and for viral infectivity.
PIs binds to HIV protease and block viral maturation. This
makes daughter viral particles immature and noninfectious.
Adverse effects:
Nausia, vomiting, diarrhoea, increase serum cholesterol and
bilirubin, dry skin, renal stones.
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24. USES
Treatment of HIV infections.
Ritonavir inhibits microsomal enzymes- prolongs plasma
half life of other PIs –permits the use of lower doses of
other PIs.
Drug interactions:
a) Metabolized by microsomal enzymes and inhibits
these enzymes. So drug interactions are common.
b) inreases the level of corticosteroids.
c) H2 antagonists and proton pump inhibitors decreases the
level of PIs.
DOSE:Saquinavir:-120 mg tid. Ritonavir: 600mg bid.
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25. 4. ENTRY INHIBITORS
Entry of the virus into the host cell can be
blocked by:
a) Fusion inhibitors
b) CCR5 receptor antagonist
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26. A) FUSION INHIBITOR(FI)
Eg: Enfuvirtide
Mechanism of action
It binds to the glycoprotien(gp41) subunit of viral
envelope on the virus and inhibits the binding of the
virus to the host cell membrane- block the entry of
the virus into the cell. Thus FIs prevents
transmission of HIV.
DOSE: 90mg s.c. twice daily
Adverse effect: Local reaction at injection site, skin
rashes, pneumonia like manifestation
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27. B) CCR5 RECEPTOR ANTAGONIST
Eg: Maraviroc
Mechanism of action:
CCR5 is a co-receptor involved in fusion and entry of
virus into CD4 cells.
Maraviroc binds to CCR5 receptors and blocks the
entry of HIV into the cells.
Adverse effects:
Nausea, vomiting, abdominal pain, constipation,
dizziness, rashes, insomnia, postural hypotension,
cough.
DOSE:300 mg bid.
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28. 5. INTEGRASE INHIBITORS
Eg: Raltegravir, elvitegravir
Mechanism of action:
Integrase is a viral enzyme necessory for viral
replication in both HIV-1 and HIV-2 viruses.
Integrase inhibitors binds to integrase and prevents
integration of HIV-DNA into the chromosome of host
cells.
Adverse effects:
Nausea, headache, dizziness, vertigo, abdominal pain,
constipation, fatigue, raised creatinine kinase.
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29. PREVENSION OF AIDS
Know your and your partners HIV status by
getting tested regularly,
Avoid injectable illegal drugs,
Avoid sharing drug needles and syringes,
Avoid intoxication from drugs or alcohol.
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30. REFERENCES
Clinical pharmacy and therapeutics by ROGER
WALKER AND CATE WHITTLESEA.
Essentials of medical pharmacology by
KD TRIPATHI
Medical pharmacology by
PADMAJA UDAYKUMAR
Pharmacological basis of therapeutics by
GOODMAN and GILMAN’S.
Clinical pharmacy and therapeutics by
HERFINDAL GOURLEY HART.
Avery’s drug treatment by
SPEIGHT HOLFORD.
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