This document provides information on HIV/AIDS including:
- HIV is a retrovirus that causes AIDS by infecting CD4 cells. It can be managed but not cured.
- AIDS is the late stage of HIV infection when the immune system is severely damaged.
- The natural history of the virus is described from its discovery in 1981 through treatments developed.
- The virus's structure and life cycle involve invading cells and integrating its DNA for dormancy.
- Transmission occurs through bodily fluids like blood, semen, breastmilk. Testing and treatment can control spread.
2. HIV
• “Human immunodeficiency virus” is a lentivirus that causes
the acquired immunodeficiency syndrome, a condition in
humans in which progressive failure of the immune system
allows life-threatening opportunistic infections and cancers.
• A unique type of virus (a retrovirus)
• Invades the helper T cells (CD4 cells) in the body of the host
(defense mechanism of a person)
• Preventable, managable but not curable.
2
3. AIDS
• “Acquired Immunodeficiency Syndrome”
• HIV is the virus that causes AIDS
• Disease limits the body’s ability to fight infection due to
markedly reduced helper T cells.
• Persons with positive HIV serology who have ever had a CD4
lymphocyte count below 200 cells/mcL or a CD4 lymphocyte
percentage below 14% are considered to have AIDS.
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4. Natural History of HIV/AIDS
• HIV was first clinically observed in 1981 in the United States
• 1982 – First use of term “AIDS”
• 1983 – Virus isolated and identified.
• 1985 – HIV Ab testing available.
• 1987 – First FDA approved drug (Zidovudine) NRTI.
• 1988 – World Health Organization(WHO) Declared December 1st
as “World AIDS Day”
• 37.0 million people living with HIV/AIDS worldwide in spt-2015
• 1.7million people died of AIDS-related illnesses worldwide in
2015
• South Africa was the 1st country having 6,200,000 people living
wth HIV.
• India was the 3rd country having 2,400,000 people living with HIV
4
5. Structure and life cycle of HIV
• HIV is a retrovirus
– Contains two strands of
(+)ssRNA
• Contains reverse transcriptase
and integrase.
– Integrase helps in the
insertion of HIV DNA into
host DNA
• Infects helper T cells and
macrophages
5
6. • The outer membrane contains the proteins gp120 and gp41. Both
are important to adsorption and penetration.
• Gp120 binds to the transmembrane protein CD4 on the host cell
and then is removed by conformational changes.
• Gp41 then pulls the virus and host cell together allowing the
membranes to fuse.
• The capsid breaks down and the viral RNA and enzymes are
release into the cell.
• Reverse transcriptase converts the viral RNA into DNA. This DNA is
known as proviral DNA
• Integrase inserts the proviral DNA into the host’s DNA. Once the
proviral DNA is part of the host’s DNA, it is known as the provirus
and can remain dormant in the DNA
6
7. • When the provirus is transcribed, three main genes are
transcribed: env, gag, and pol.
• Three non-functional poly-proteins are made from these genes,
one from the env gene, one from the gag gene, and the last one is
from a combination of the gag and pol genes.
• The first produces gp120 and gp41 which are placed onto the cell
membrane. The other two poly-proteins move to the inner cell
membrane and block out host membrane proteins. Budding
occurs in this region of the membrane.
• The gag-pol protein releases protease by autocatalysing the gag-
pol protein. Protease then cleaves reverse transcriptase,
integrase, and other proteins.
• The capsid forms, with all viral RNA, essential enzymes, and
proteins in it. The complete virus then leaves the host cell.
7
16. Blood Detection Tests
• Enzyme-Linked Immunosorbent Assay/Enzyme
Immunoassay (ELISA/EIA)
• Radio Immunoprecipitation Assay/Indirect Fluorescent
Antibody Assay (RIP/IFA)
• Polymerase Chain Reaction (PCR)
• Western Blot Confirmatory test
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17. Urine Testing
• Urine Western Blot
– As sensitive as testing blood
– Safe way to screen for HIV
– Can cause false positives in certain
people at high risk for HIV
17
18. Oral Testing
• Orasure
– The only FDA approved HIV
antibody.
– As accurate as blood testing
– Draws blood-derived fluids
from the gum tissue.
– NOT A SALIVA TEST!
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22. Nucleoside/Nucleotide Reverse Transcriptase Inhibitors(NRTI’s)
Agent Approved Dose frequency
Zidovudine 3/87 300mg od
Didanosine 10/91 250,400mg od
Stavudine 6/94 15,20,30mg bd
Lamivudine 11/95 100,150,300mg BD
Abacavir 12/98 300mg BD
Combivir 9/97 150/300mg BD
Trizivir 11/00 150mg/300mg BD
Tenofovir 10/01 150,200,250,300
mg
OD
Emtricitabine 7/03 200mg OD
Epzicom 8/04 300mg/600mg OD
Truvada 8/04 200mg/300mg OD 22
23. NRTI Mechanism of Action
• NRTIs must first undergo intracellular phosphorylation to be
active
• NRTIs inhibit the viral reverse transcriptase enzyme
– Enzyme responsible for transcribing viral RNA into double
stranded DNA
• NRTIs mimic other nucleosides and are incorporated into the
DNA strand
• They prevent the addition of the natural nucleosides into the
DNA strand
• This halts the production of new virions
Clinical Pharmacology 2007. Gold Standard, Inc.
23
24. NRTI Adverse Effects
Zidovudine
• Bone marrow suppression (anemia/
neutropenia), Nausea, Nail discoloration
Abacavir
Hypersensitivity reaction: fever, rash,
fatigue, malaise, nausea, vomiting, diarrhea,
loss of appetite, pharyngitis
Lamivudine Generally well-tolerated
Emtricitabine Hyperpigmentation of palms and soles
Stavudine
• Peripheral neuropathy, Pancreatitis,
Increased triglycerides
Didanosine
• Pancreatitis, Peripheral neuropathy,
Diarrhea
Tenofovir • GI upset, Flatulence, Nephrotoxicity
NRTI Adverse Effects
25. Non-Nucleoside Reverse Transcriptase
Inhibitors (NNRTIs)
Agent Approved Dose frequency
Nevirapine
(Immediate Release)
6/96 200mg
400mg
OD x14Days then
OD
Delavirdine 4/97 400mg TID
Efavirenz 9/98 400mg BD
Nevirapine
(Extended Release)
6/11 400mg OD
Rilpivirine 20-May-11 25mg OD
Etravirine 18-Jan-08 200mg q12hrly
25
26. NNRTI Adverse Effects
• Nevirapine:
– Rash (7%), increased transaminase levels, hepatitis
• Hepatotoxicty more common in women with pretreatment CD4+
cell counts > 250 cells/mm3 , men with CD4+ cell counts > 400
cells/mm3 and patients co-infected with hepatitis B or C
• Monitor LFTs minimally at baseline, 2 weeks, monthly for the 1st
3 months in all patients
• Efavirenz:
– Rash (1.7%), increased transaminase levels, CNS side
effects (e.g. vivid dreams, dizziness, drowsiness)
NNRTI Adverse Effects
27
28. PI Mechanism of Action
• Protease enzyme is responsible for cleaving
(cutting up) larger polyproteins into structural
proteins and reverse transcriptase enzyme
• Protease is needed to form a fully mature,
functional virus that is able to replicate and
produce more virus
• Protease inhibitors prevent this enzyme from
doing its job in the later steps of the viral life
cycle
Clinical Pharmacology 2007. Gold Standard, Inc.
29
29. PI Adverse Effects
Amprenavir/fos-amprenavir
GI intolerance, rash, oral
paresthesias
Atazanavir Hyperbilirubinemia
Indinavir Nephrolithiasis, hyperbilirubinemia
Lopinavir/ritonavir Nausea, diarrhea, pancreatitis
Nelfinavir Diarrhea
Ritonavir
GI intolerance, paresthesias,
asthenia, taste perversion, hepatitis
Saquinavir GI intolerance
Tipranavir
GI intolerance, hepatitis, rash,
intracranial hemorrhage
Darunavir GI intolerance, rash
30. Fusion Inhibitor
Fusion Inhibitor Mechanism of Action :
• Inhibits entry of HIV into the CD4 cell
• Enfuvirtide binds to glycoprotein gp41 (a protein on
the viral membrane)
• This binding prevents a change in the shape of the
membrane protein and prevents fusion of the virus
and the CD4 cell membrane
Agent Approved Dose frequency
Enfuvirtide
(T-20, Fuzeon)
3/2003 90mg(IV) BID
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31. Penetration blockers
Mechanism of action:
Maraviroc is a CCR5 inhibitor that binds to the
host cell through CCR5 receptors. It is only active
in patients who have virions that use CXCR5 for
cell entry.
Agent Approved Dose frequency
Maraviroc 8/2007 300mg BID
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32. HIV integrase strand transfer inhibitors(INSTI)
Agent Approved Dose frequency
Raltegravir 12--Oct-07 400mg BD
Dolutegravir 13-August-13 500mg OD
• Mechanism of action:
Inhibits catalytic activity of integrase,an HIV
encoded enzyme required for viral replication.
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33. Initial Treatment:
Preferred Components
*Avoid in pregnant women and women with significant pregnancy potential.
**Emtricitabine can be used in place of lamivudine and vice versa.
• Efavirenz*
OR
• Atazanavir + ritonavir
• Fosamprenavir + ritonavir (BID)
• Lopinavir/ritonavir (BID)
NNRTI Option
PI Options
Tenofovir +
emtricitabine**
OR
Zidovudine +
lamivudine**
+
NRTI Options
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34. Initial Treatment:
Alternative Components
*Nevirapine should not be initiated in women with CD4 counts >250 cells/mm3 or men with CD4 counts >
400 cells/mm3
**Atazanavir must be boosted with ritonavir if used in combination with tenofovir
• Nevirapine*
OR
• Atazanavir**
• Fosamprenavir
• Fosamprenavir + ritonavir (QD)
• Lopinavir/ritonavir (QD)
NNRTI Option
PI Options
Abacavir +
lamivudine
Or
Didanosine +
(emtricitabine or
lamivudine)
NRTI Options
+
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35. Multi-class Combination Products
Agent Approved Dose frequency
Atripla:
(efavirenz/
emtricitabine /
tenofovir disoproxil fumarate )
12-July-06 600mg/
200mg /
300mg
OD (E S)
Complera :
( emtricitabine/
rilpivirine/
tenofovir disoproxil fumarate )
10-August-11 200mg/
25mg /
300mg
OD (W M)
Stribild :
( elvitegravir/
cobicistat/
emtricitabine/
tenofovir disoproxil fumarate )
27-August-12 150mg/
150mg/
200mg /
300mg
OD (W M)
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36. Drug interactions
Agents Comment
Stavudine + zidovudine Both thymidine analogs; antagonistic
Stavudine + didanosine Increased risk of toxicities such as lactic acidosis
and pancreatitis; may be considered when no
other options available and potential benefits
outweigh the risks.
Emtricitabine + lamivudine Similar resistance profiles; no potential benefit
Efavirenz in pregnancy Teratogenic
Amprenavir oral solution Contraindications due to propylene glycol
content
Amprenavir + fosamprenavir Amprenavir is active component of both drugs
Atazanavir + indinavir Potential for additive hyperbilirubinemia
37. Methods of control
Preventive measures:
• Refraining from unprotected Intercourse.
• Refraining from intravenous drug use.
• People who have HIV infection should not donate
plasma, blood, organs for transplantation, tissue or
cells.
• All pregnant women must be counselled about HIV
early in pregnancy and encouraged to undertake an
HIV test as a routine part of standard antenatal care.
• Those found to be HIV-positive take a course of ARV
treatment, to reduce the risk of their infant being
infected. 38
38. Methods of control (cont.)
• Care must be taken in handling, using and disposing of
needles or other sharp instruments.
• WHO recommends immunization of asymptomatic
HIVinfected children with the EPI vaccines; those who are
symptomatic should not receive BCG vaccine.
• Live Measles-Mumps-Rubella and polio vaccines are
recommended for all HIV-infected children.
• HIV testing and counselling is an important intervention for
raising awareness of HIV status, promoting behavioural
change and diagnosing HIV infection.
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39. Conclusion
• HIV/AIDS is a world epidemic. Although making new
advances in combating this virus, there are many new
infections every year. All should know what how it spreads
and how to prevent it. Should take a HIV/AIDS test if
involved in any risky behaviors. And also should tell others
the importance of getting tested and prevention.
• There is no cure for this virus, so there is no room for
ignorance on this matter.
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40. REFERENCE
Pharmacotherapy, A Pathophysiologic approach by J.T.Dipiro 8 th
edition, page.no:2065-2081
emedicine.medscape.com/article/1533218-Author R Chris Rathbun
Aberg, J. A., Kaplan, J. E., Libman, H., "Primary Care Guidelines for
the Management of Persons Infected with Human
Immunodeficiency Virus: 2009 Update by the HIV Medicine
Association of the Infectious Diseases Society of America.
Book of MEDICINE 4th edition, Authors K George Mathew, Praveen
Aggarwal, Pg.no.223-234 Anti Retroviral therapy.