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Arwa M. Amin Mostafa
PhD, M. Pharm Clinical Pharm, Dip Management, BSc. Pharm.
HIV
Infection
A rwa M. A min
What We will Discuss Today?
• What is HIV? What are the opportunistic Infections? What is AIDS?
• What are the body fluids that HIV exist in them?
• What are the most common HIV transmission Routes?
• What are HIV Transmission High risk populations?
• What is the Etiology and pathogenesis of HIV infection?
• What are the Complications of HIV infection?
• How to diagnose HIV?
• What are the stages of HIV Disease?
• What are the Clinical Presentations of HIV Disease?
• How to Treat HIV?
• How to Prevent HIV?
A rwa M. A min
HIV
• Human Immunodeficiency Virus (HIV) is a human
retrovirus infection which invades human the T-helper
lymphocytes (CD4 Cells or CD4+ Cells) immunity Cell.
• CD4 Cells regulates Immune responses by stimulating
other immune cells such as macrophages, B
lymphocytes (B cells), and CD8 T lymphocytes (CD8
cells) to fight infection.
CD4 (cluster of differentiation 4)
A rwa M. A min
HIV
• HIV infection damages Human Immunity which affects
body’s ability to fight other infections (viral, bacterial,
fungal or parasites) and Infections-related-Cancers.
• HIV infection is PREVENTABLE.
• HIV infection is NOT CURABLE, but Antiretroviral
Therapy (ART) can help patients to live longer and
healthier.
A rwa M. A min
AIDS
• Acquired Immune Deficiency Syndrome (AIDS) is the
Final Stage of HIV disease (Symptomatic stage) where
HIV infection has Severely Lowered CD4+ cells counts
and badly damaged the host immunity making him at
very high risk for opportunistic infections.
• AIDS is a LIFE threatening condition.
A rwa M. A min
Opportunistic Infections (OIs)
• opportunistic infections (OIs) are
infections caused by pathogens that take
the advantage of very weakened host
immunity opportunity.
• OIs pathogens usually Do Not cause
disease in Healthy immune system.
However, OIs occurs ↑↑ often and ↑↑ severe
in HIV patients.
A rwa M. A min
Opportunistic Infections (Ois)
• Examples of OIs which occur in HIV patients:
• Fungal Infections: Candidiasis, Cryptococcosis, Aspergillosis
• Bacterial Infections: Tuberculosis, Pneumonia, Mycobacterium
Avium
• Viral Infections: Herpes simplex virus, Varicella zoster virus,
Cytomegalovirus.
• Parasitic Infections: Toxoplasmosis, Cryptosporidiosis
A rwa M. A min
HIV Timeline
1981 – HIV outbreak occurred among Homosexual Men in
New York and California.
1982 – The name AIDS was created.
1984 – HIV was identified as the causative infection of AIDS
1985 – ELISA test was developed to test HIV Antibodies
1987 – Zidovudine; First Antiretroviral Drug was available
for HIV treatment
1988 – The First World AIDS Day (1 December)
1992 – The first Combination of HIV Therapy was introduced
2002 - First rapid diagnostic HIV test kit was approved by
FDA
A rwa M. A min
HIV Epidemiology
• HIV/AIDS is a Global pandemic.
• 76.1 million people have become infected with HIV since the
start of the epidemic.
 34.5 million adults
 17.8 million women (15+ years)
 2.1 million children (<15 years)
• 36.7 million people globally are living with HIV in 2016.
• 35.0 million people have died from AIDS-related illnesses
since the start of the epidemic.
• 1.8 million people became newly infected with HIV in 2016.
• 1 million people died from AIDS-related illnesses in 2016.
UNAIDS: Fact sheet - Latest statistics on the status of the AIDS epidemic, http://www.unaids.org/en/resources/fact-sheet
A rwa M. A min
HIV Epidemiology
UNAIDS: Fact sheet - Latest statistics on the status of the AIDS epidemic,
http://www.unaids.org/en/resources/fact-sheet
A rwa M. A min
HIV Statistics
UNAIDS: Fact sheet - Latest statistics on the status of the AIDS epidemic, http://www.unaids.org/en/resources/fact-sheet
A rwa M. A min
Types of HIV
• HIV occurs as two types; HIV-1 and HIV-2.
• Both types can be transmitted by most likely HIV
transmission routes.
• HIV-1 is the Most Common Type of
HIV and the infectious agent which
caused the global AIDS epidemic.
• HIV-2 is Rare type of HIV but
results in AIDS as well.
A rwa M. A min
Body fluids with High HIV Concentration
• Blood
• Semen (seminal fluids)
• Anal secretions
• Vaginal secretion
• Breast Milk
Some body fluids have High concentration of HIV
• These fluids have ↑↑ Chances of HIV infection
transmission.
A rwa M. A min
Body fluids with Low HIV Concentration
• Saliva
• Tears
• Urine
• Sweat
Some body fluids have Low concentration of HIV
• Transmission of the infection through these fluids
is unlikely
If Blood or open wounds are present with these fluids,
there are chances of HIV transmission.
A rwa M. A min
Transmission Routes of HIV Infection
• Un-protected sex with HIV infected
person.
• Sexual Abuse (e.g. Rape)
• Sharing contaminated Needles (e.g. Tattoo
or piercing needles), syringes, blades or
sharp equipment.
• HIV can live in used needle up to 42
days depending on Temperature &
other factors.
HIV can be Transmitted by ..? Most Likely Routes
A rwa M. A min
Transmission Routes of HIV Infection
• Blood Transfusion or Blood products
contaminated with HIV.
• Organ or Tissue transplant contaminated
with HIV.
• However, there is low risk of this
transmission route because organ donors go
under extensive investigations and testing.
• IV drug abuse.
HIV can be Transmitted by ..? Most Likely Routes
A rwa M. A min
Transmission Routes of HIV Infection
• Mother-to-child-transmission
(MTCT) which is the transmission of
HIV from the mother to the child
during Pregnancy, Delivery or
Breastfeeding.
HIV can be Transmitted by ..? Most likely Routes
A rwa M. A min
Transmission Routes of HIV Infection
• Eating food pre-chewed by HIV infected person.
• If dental/gum wound is present in the HIV infected
person and the person who re-chewed the pre-
chewed food.
• Bitten (with skin break) by HIV infected person.
• Contact of wound (Broken skin) with HIV infected
blood or fluids.
• open-mouth kissing if sores or bleeding gums are
present.
HIV can be Transmitted by ..? Less Likely Routes
A rwa M. A min
Transmission Routes of HIV Infection
HIV is Not Transmitted by ..?
• Hugging, social kissing* or holding hands
• Sharing swimming pool
• Sharing Toilets seats
• Sharing food utensils
• Mosquito or Insects bites
*Social Kissing: Closed mouth kissing
A rwa M. A min
HIV Transmission: High Risk Populations
• Homosexual Men (Gay) and Bisexual Men.
• IV Drug abusers.
• Young People (20 – 29 ) years old.
• HIV negative Spouse of HIV positive person.
• New-born Babies of HIV Mother.
• Women working in sex.
• Health-care workers (risk of being accidently wounded
by HIV contaminated needles or sharp objects).
• Researchers working with HIV biosamples.
A rwa M. A min
HIV Transmission: High Risk Populations
This pie chart shows new HIV
diagnoses in the United States
in 2016 by transmission
category
Figure source: CDC, Statistics center, HIV in the United
States: At A Glance,
https://www.cdc.gov/hiv/statistics/overview/ataglance.h
tml
A rwa M. A min
Pathogenesis of HIV: HIV Structure
A rwa M. A min
Pathogenesis of HIV: HIV Structure
A rwa M. A min
Pathogenesis of HIV: HIV Life cycle
HIV Life Cycle involves
Seven steps where HIV
uses the machinery of
CD4 cells to multiply
and spread through the
body:
1.Binding
2.Fusion
3.Reverse Transcription
4.Integration
5.Replication
6.Assembly
7.Budding
FigureSource:HIVLifeCycle,
https://aidsinfo.nih.gov/understanding
-hiv-aids/fact-sheets/19/73/the-hiv-
life-cycle
A rwa M. A min
Pathogenesis of HIV
1.Binding
Figure Source: Adapted & Modified; HIV Life Cycle, https://aidsinfo.nih.gov/understanding-hiv-aids/fact-
sheets/19/73/the-hiv-life-cycle
A rwa M. A min
Pathogenesis of HIV: HIV Life cycle
HIV Life Cycle involves
Seven steps where HIV
uses the machinery of
CD4 cells to multiply
and spread through the
body:
1.Binding
2.Fusion
3.Reverse Transcription
4.Integration
5.Replication
6.Assembly
7.Budding
FigureSource:HIVLifeCycle,
https://aidsinfo.nih.gov/understanding
-hiv-aids/fact-sheets/19/73/the-hiv-
life-cycle
A rwa M. A min
Pathogenesis of HIV
2. Fusion
Figure Source: Adapted & Modified; HIV Life Cycle, https://aidsinfo.nih.gov/understanding-hiv-aids/fact-
sheets/19/73/the-hiv-life-cycle
A rwa M. A min
Pathogenesis of HIV: HIV Life cycle
HIV Life Cycle involves
Seven steps where HIV
uses the machinery of
CD4 cells to multiply
and spread through the
body:
1.Binding
2.Fusion
3.Reverse Transcription
4.Integration
5.Replication
6.Assembly
7.Budding
FigureSource:HIVLifeCycle,
https://aidsinfo.nih.gov/understanding
-hiv-aids/fact-sheets/19/73/the-hiv-
life-cycle
A rwa M. A min
Pathogenesis of HIV
3. Reverse Transcription
Figure Source: Adapted & Modified; HIV Life Cycle, https://aidsinfo.nih.gov/understanding-hiv-aids/fact-
sheets/19/73/the-hiv-life-cycle
A rwa M. A min
Pathogenesis of HIV: HIV Life cycle
HIV Life Cycle involves
Seven steps where HIV
uses the machinery of
CD4 cells to multiply
and spread through the
body:
1.Binding
2.Fusion
3.Reverse Transcription
4.Integration
5.Replication
6.Assembly
7.Budding
FigureSource:HIVLifeCycle,
https://aidsinfo.nih.gov/understanding
-hiv-aids/fact-sheets/19/73/the-hiv-
life-cycle
A rwa M. A min
Pathogenesis of HIV
4. Integration
Figure Source: Adapted & Modified;
HIV Life Cycle,
https://aidsinfo.nih.gov/understanding
-hiv-aids/fact-sheets/19/73/the-hiv-
life-cycle
A rwa M. A min
Pathogenesis of HIV: HIV Life cycle
HIV Life Cycle involves
Seven steps where HIV
uses the machinery of
CD4 cells to multiply
and spread through the
body:
1.Binding
2.Fusion
3.Reverse Transcription
4.Integration
5.Replication
6.Assembly
7.Budding
FigureSource:HIVLifeCycle,
https://aidsinfo.nih.gov/understanding
-hiv-aids/fact-sheets/19/73/the-hiv-
life-cycle
A rwa M. A min
Pathogenesis of HIV
5. Replication
Figure Source: Adapted & Modified; HIV Life Cycle, https://aidsinfo.nih.gov/understanding-hiv-aids/fact-sheets/19/73/the-
hiv-life-cycle
A rwa M. A min
Pathogenesis of HIV: HIV Life cycle
HIV Life Cycle involves
Seven steps where HIV
uses the machinery of
CD4 cells to multiply
and spread through the
body:
1.Binding
2.Fusion
3.Reverse Transcription
4.Integration
5.Replication
6.Assembly
7.Budding
FigureSource:HIVLifeCycle,
https://aidsinfo.nih.gov/understanding
-hiv-aids/fact-sheets/19/73/the-hiv-
life-cycle
A rwa M. A min
Pathogenesis of HIV
6. Assembly
Figure Source: Adapted & Modified; HIV Life Cycle, https://aidsinfo.nih.gov/understanding-hiv-aids/fact-sheets/19/73/the-
hiv-life-cycle
A rwa M. A min
Pathogenesis of HIV: HIV Life cycle
HIV Life Cycle involves
Seven steps where HIV
uses the machinery of
CD4 cells to multiply
and spread through the
body:
1.Binding
2.Fusion
3.Reverse Transcription
4.Integration
5.Replication
6.Assembly
7.Budding
FigureSource:HIVLifeCycle,
https://aidsinfo.nih.gov/understanding
-hiv-aids/fact-sheets/19/73/the-hiv-
life-cycle
A rwa M. A min
Pathogenesis of HIV
7. Budding
Figure Source: Adapted & Modified; HIV Life Cycle, https://aidsinfo.nih.gov/understanding-hiv-aids/fact-sheets/19/73/the-
hiv-life-cycle
A rwa M. A min
Pathogenesis of HIV: HIV Life cycle
HIV Life Cycle involves
Seven steps where HIV
uses the machinery of
CD4 cells to multiply
and spread through the
body:
1.Binding
2.Fusion
3.Reverse Transcription
4.Integration
5.Replication
6.Assembly
7.Budding
FigureSource:HIVLifeCycle,
https://aidsinfo.nih.gov/understanding
-hiv-aids/fact-sheets/19/73/the-hiv-
life-cycle
A rwa M. A min
Complications of HIV Infection
• Death: ↑↑ Morbidity & ↑↑ Mortality
• HIV infected patients face death due to opportunistic
Infections, severe CNS conditions and infections-
related-cancers.
• CNS Conditions occur when HIV enters the CNS and
cause complications such as:
• HIV Encephalopathy
• AIDS Dementia complex
• HIV-associated Progressive Encephalopathy (HPE)
A rwa M. A min
HIV Diagnosis: laboratory Tests
• ELISA TEST
 Tests HIV Antibodies NOT HIV
 Samples: Blood, Serum, Plasma, Saliva, Urine
 Tests 2 – 8 weeks after infection
 Infected person can be Negative between few
weeks to few months after infection.
 If ELISA results showed HIV-Positive results,
Western blot Cross check should be done to
confirm the results.
 If Western blot cross check showed HIV-Positive
results → HIV infection is confirmed.
ELISA: enzyme-linked immunosorbent assay (ELISA)
A rwa M. A min
HIV Diagnosis: laboratory Tests
Quick HIV Diagnosis Tests
• Rapid HIV Antibodies Test
 Rapid & Easy to perform test for HIV Antibodies
 Detection within 30 minutes.
 Sample: Finger prick Blood.
• OraQuick
 FDA-approved oral swab in-home test for HIV-1 and
HIV-2.
 Sample: Oral swab.
 Rapid home test to test HIV Antibodies.
 Can be done in 20 minutes.
 If Positive results, it should be confirmed by Blood test
A rwa M. A min
HIV Diagnosis: laboratory Tests
Viral Load Test (VLT)
Measures the amount of HIV-RNA in blood (amount of
HIV in blood).
Number of copies of HIV-RNA in a milliliter of blood.
Can be tested 1 – 4 weeks from HIV Exposure.
Should be used in the evaluation of the efficacy of ART.
Viral Load should fall within 3 – 6 months of Treatment.
ART: Antiretroviral Therapy
A rwa M. A min
HIV Diagnosis: laboratory Tests
Viral Load Test (VLT)
What does ↑↑ Viral Load Number indicate?
↑↑ HIV amount in Blood
↑↑ Fast Damage of CD4 cells (CD4 Cell count will fall)
↑↑ Risk of Developing AIDS & Death.
Patient may Not be taking his ART medications.
Patient is Not responding well to ART.
ART: Antiretroviral Therapy
A rwa M. A min
HIV Diagnosis: Laboratory Tests
• CD4 cell counts:
Since HIV destroys CD4 Cells, the count of
CD4 cells is important biomarker to assess:
 State of patient’s Immune system
 HIV disease progression
 Efficacy of HIV Therapy
Normal blood values for CD4 cells is
(500–1500 cells/mm3).
Should be measured every 3 – 6 months
in the First 2 years of HIV infection.
A rwa M. A min
HIV Diagnosis: Laboratory Tests
CD4 cell counts
What does ↓↓ CD4 Cell counts indicate?
↑↑ Damage of CD4 cells.
↑↑ Risk of Developing AIDS & Death.
Patient may Not be taking his ART medications.
Patient is Not responding well to ART.
ART: Antiretroviral Therapy
A rwa M. A min
Upon contracting HIV infection, infected person doesn’t have signs
which indicate the infection. However, while signs are absent,
infection continues to damage CD4 Cells and immune system.
Stages of HIV Infection
Acute HIV
Infection
•Flu-Like
symptoms
•Lasts for 2 – 4
weeks of
contracting HIV
infection
AIDS
•CD4 Cell counts
below 200
cells/mm3
•↑↑ Risk of
Opportunistic
Infections
Chronic HIV
Infection (Clinical
Latency)
• Chronic HIV
Infection after
Acute phase
• Can last for decade
(≈ or > 10 years)
HIV Infection has Three Main stages
A rwa M. A minFigure source: https://commons.wikimedia.org/wiki/File:Hiv-timecourse_copy.svg
A rwa M. A min
Figure source: The Stages of HIV Infection, https://aidsinfo.nih.gov/understanding-hiv-aids/fact-sheets/19/46/the-stages-of-hiv-infection
A rwa M. A min
HIV Diagnosis: Symptoms of Acute HIV Infection
• Flu-like symptoms
• High fever
• Sore throat
• Headache
• Lymphadenopathy
• Stomach up set, Nausea,
Vomiting & Diarrhea
• Skin rashes
• Joints pain
• Muscle pain
• Tiredness, Malaise & Fatigue
• Weight Loss
• Liver & Spleen Enlargement
•Acute HIV Infection symptoms are relatively Non-specific.
•HIV AB Test often Negative, however, becomes Positive
within 3 – 6 Months.
AB: Antibodies
A rwa M. A min
HIV Diagnosis: Clinical
Manifestations of
Acute HIV Infection
A rwa M. A min
HIV Diagnosis: Clinical Manifestations of Chronic HIV Infection
•Chronic HIV Infection (Clinical Latency) is
Asymptomatic stage i.e. Free of Symptoms.
•HIV is growing very slowly.
•HIV Anti-Bodies are detectable in blood (Positive).
•HIV level in blood may drop to Low Levels, but
PATIENT still can SPREAD HIV to OTHERS.
•There might be swollen glands.
•How long does the HIV Clinical Latency take?
•It depends on the Patient’s immunity & HIV
treatment.
A rwa M. A min
HIV Diagnosis: AIDS Clinical Manifestations
• AIDS is the third and Symptomatic stage of HIV where patient
is at very high risk of contracting Opportunistic Infections.
• CD4 Count in AIDS patient < 200/mm3
• Patient will have symptoms such as:
 Rapid weight Loss
• Respiratory signs &
symptoms
 SOB & Cough
• GI symptoms
 Chronic Diarrhea, Nausea &
Vomiting
• Skin
 Skin Lesions
 Poor wound healing
 Excessive sweating
A rwa M. A min
Figure Source: Nursing Education
Consultant,
https://www.pinterest.dk/pin/13440437
0106704850/visual-
search/?x=16&y=12&w=530&h=398
Clinical
Manifestations
of AIDS
A rwa M. A min
Management of HIV
HIV is NOT CURABLE.
Goals of HIV Therapy are:
Improving patient’s quality of life.
Reducing Morbidity and Mortality.
Restoring patient’s CD4 cell counts.
Preventing HIV replication
 Reducing HIV Viral Load to undetectable level (<50 copies/mL).
Preventing and treating opportunistic infections.
Preventing HIV transmission from infected subjects.
A rwa M. A min
Management of HIV
Non-Pharmacological Treatment of HIV:
 Patient Education
 Providing Social Support to the patient
 Regular Exercising
 Adequate rest
 Avoiding Alcohol Drinking
 Smoking Cessation
 Eating healthy and Nutritious Diet
A rwa M. A min
Management of HIV: Pharmacological Management
HIV Pharmacological Treatment:
 HIV Pharmacological treatment is achieved by using
Antiretroviral Therapy (ART).
 ART is evolving quickly.
 More than 30 Antiretroviral drugs.
 ART consists of combination of three HIV antiretroviral
drugs from Two pharmacological Classes.
A rwa M. A min
Management of HIV: Pharmacological Management
Benefits of using ART:
Preventing HIV from replication.
ART Combination attacks HIV life cycle at different steps.
Synergistic effect
↑↑ CD4 cell counts.
↓↓ Risk of HIV-Drug-resistance strains development.
↓↓ side-effects of high doses of ART drugs (↓↓ Drug Toxicity)
↓↓ HIV transmission
A rwa M. A min
Management of HIV: Pharmacological Management
Main Aim of ART
CD4Counts
ViralLoad
ART
ART: Antiretroviral Therapy
A rwa M. A min
Management of HIV: Pharmacological Management
When to Initiate ART in HIV infected subjects?
DHHS Guidelines of ART* use (2017):
ART is recommended for all individuals with HIV,
regardless of CD4 cell counts to reduce morbidity,
mortality and to prevent transmission.
*DHHS Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV, 2017, available at
https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv/0
A rwa M. A min
Management of HIV: Pharmacological Management
Main Classes of HIV Antiretroviral Drugs:
 Entry inhibitors; e.g. Enfuvirtide
 Reverse transcriptase inhibitors
NRTIs: e.g. Tenofovir, Emtricitabine (Truvada®: Tenofovir/Emtricitabine)
NNRTIs: e.g. Efavirenz, Nevirapine
 Integrase strand transfer inhibitors (InSTIs); Raltegravir,
Dolutegravir
 HIV protease inhibitors (PIs); e.g. Darunavir, Ritonavir,
Atazanavir,
NRTIs: Nucleoside reverse transcriptase inhibitors, NNRTIs: Non-nucleoside reverse transcriptase inhibitors
A rwa M. A min
Management of HIV: Pharmacological Treatment
Examples of ART Combinations
Examples of ART Combinations
• HIV-PI based:
Darunavir + Ritonavir + Tenofovir + Emtricitabine
• InSTI based:
Raltegravir + Tenofovir + Emtricitabine
Preferred
Combinations
• NNRTI based:
Efavirenz + Tenofovir + Emtricitabine
• HIV-PI based:
Atazanavir + Ritonavir + Tenofovir +
Emtricitabine
Alternative
Combinations
InSTIs: Integrase strand Transfer Inhibitor, NNRTI: Non-nucleoside reverse transcriptase inhibitor, PI: Protease Inhibitor
A rwa M. A min
Common Side effects of HIV Antiretroviral Drugs
Table source: The potential anesthetic threats, challenges and intensive care considerations in patients with HIV infection,
http://www.jpbsonline.org/viewimage.asp?img=JPharmBioallSci_2013_5_1_10_106554_b3.jpg
A rwa M. A min
Management of HIV in Pregnancy
• HIV infected women should be treated regardless
of pregnancy status.
• ART for pregnant HIV positive woman is Not
contraindicated.
• ART can reduce Perinatal Transmission.
• Safety, Efficacy, and Pharmacokinetic (PK) data
of antiretroviral drugs should be considered when
designing the ART combination in Pregnancy.
• E.g. of Preferred ART Combination in Pregnancy:
 Two NRTI: Tenofovir + Emtricitabine
 Two PIs: Darunavir + Ritonavir
ART: Antiretroviral Therapy, NRTIs: Nucleoside reverse transcriptase inhibitor, PIs: Protease Inhibitor
A rwa M. A min
Management of HIV: Monitoring of ART
Plasma HIV-RNA levels (Viral
Load) and CD4 cell counts
periodical measurement is
necessary:
• To determine when to
initiate or modify
antiretroviral treatment
regimens.
• To determine HIV disease
progression.
A rwa M. A min
HIV Prevention
• There is NO Vaccination for preventing HIV.
• Prevent Sexual HIV Transmission
 Abstinence and Marital Fidelity are the best way to
prevent sexual HIV transmission.
 Ensure Pre-marital HIV Testing
 Ensure mutual Non-HIV infected marriage
 Condom use ↓↓ HIV transmission by approximately 80%.
 Male circumcision ↓↓ transmission risk in circumcised Men.
• Avoid IV Drug abuse.
A rwa M. A min
HIV Prevention
• Educating the public on the prevention of HIV.
• Ensure proper HIV testing of Blood products /
transplants and safe blood transfusion.
• Prevent Mother-to-Child-transmission of HIV.
• Ensure Proper Hygiene and using sterile personal
sharp objects (Needles & Blades).
• Avoid sharing Needles or Sharp objects
e.g. Blades, shavings, needles, razors
• Prevent HIV transmission in Healthcare settings.
A rwa M. A min
•*Proper Sterilization of
Surgical and Dental equipment.
Preventing
HIV
Transmission
in Health-
Care Setting
Figure Source:
https://www.pinterest.co.uk/pi
n/320600067194445053/
A rwa M. A min

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Human Immunodeficiency Virus (HIV) Infection

  • 1. Arwa M. Amin Mostafa PhD, M. Pharm Clinical Pharm, Dip Management, BSc. Pharm. HIV Infection
  • 2. A rwa M. A min What We will Discuss Today? • What is HIV? What are the opportunistic Infections? What is AIDS? • What are the body fluids that HIV exist in them? • What are the most common HIV transmission Routes? • What are HIV Transmission High risk populations? • What is the Etiology and pathogenesis of HIV infection? • What are the Complications of HIV infection? • How to diagnose HIV? • What are the stages of HIV Disease? • What are the Clinical Presentations of HIV Disease? • How to Treat HIV? • How to Prevent HIV?
  • 3. A rwa M. A min HIV • Human Immunodeficiency Virus (HIV) is a human retrovirus infection which invades human the T-helper lymphocytes (CD4 Cells or CD4+ Cells) immunity Cell. • CD4 Cells regulates Immune responses by stimulating other immune cells such as macrophages, B lymphocytes (B cells), and CD8 T lymphocytes (CD8 cells) to fight infection. CD4 (cluster of differentiation 4)
  • 4. A rwa M. A min HIV • HIV infection damages Human Immunity which affects body’s ability to fight other infections (viral, bacterial, fungal or parasites) and Infections-related-Cancers. • HIV infection is PREVENTABLE. • HIV infection is NOT CURABLE, but Antiretroviral Therapy (ART) can help patients to live longer and healthier.
  • 5. A rwa M. A min AIDS • Acquired Immune Deficiency Syndrome (AIDS) is the Final Stage of HIV disease (Symptomatic stage) where HIV infection has Severely Lowered CD4+ cells counts and badly damaged the host immunity making him at very high risk for opportunistic infections. • AIDS is a LIFE threatening condition.
  • 6. A rwa M. A min Opportunistic Infections (OIs) • opportunistic infections (OIs) are infections caused by pathogens that take the advantage of very weakened host immunity opportunity. • OIs pathogens usually Do Not cause disease in Healthy immune system. However, OIs occurs ↑↑ often and ↑↑ severe in HIV patients.
  • 7. A rwa M. A min Opportunistic Infections (Ois) • Examples of OIs which occur in HIV patients: • Fungal Infections: Candidiasis, Cryptococcosis, Aspergillosis • Bacterial Infections: Tuberculosis, Pneumonia, Mycobacterium Avium • Viral Infections: Herpes simplex virus, Varicella zoster virus, Cytomegalovirus. • Parasitic Infections: Toxoplasmosis, Cryptosporidiosis
  • 8. A rwa M. A min HIV Timeline 1981 – HIV outbreak occurred among Homosexual Men in New York and California. 1982 – The name AIDS was created. 1984 – HIV was identified as the causative infection of AIDS 1985 – ELISA test was developed to test HIV Antibodies 1987 – Zidovudine; First Antiretroviral Drug was available for HIV treatment 1988 – The First World AIDS Day (1 December) 1992 – The first Combination of HIV Therapy was introduced 2002 - First rapid diagnostic HIV test kit was approved by FDA
  • 9. A rwa M. A min HIV Epidemiology • HIV/AIDS is a Global pandemic. • 76.1 million people have become infected with HIV since the start of the epidemic.  34.5 million adults  17.8 million women (15+ years)  2.1 million children (<15 years) • 36.7 million people globally are living with HIV in 2016. • 35.0 million people have died from AIDS-related illnesses since the start of the epidemic. • 1.8 million people became newly infected with HIV in 2016. • 1 million people died from AIDS-related illnesses in 2016. UNAIDS: Fact sheet - Latest statistics on the status of the AIDS epidemic, http://www.unaids.org/en/resources/fact-sheet
  • 10. A rwa M. A min HIV Epidemiology UNAIDS: Fact sheet - Latest statistics on the status of the AIDS epidemic, http://www.unaids.org/en/resources/fact-sheet
  • 11. A rwa M. A min HIV Statistics UNAIDS: Fact sheet - Latest statistics on the status of the AIDS epidemic, http://www.unaids.org/en/resources/fact-sheet
  • 12. A rwa M. A min Types of HIV • HIV occurs as two types; HIV-1 and HIV-2. • Both types can be transmitted by most likely HIV transmission routes. • HIV-1 is the Most Common Type of HIV and the infectious agent which caused the global AIDS epidemic. • HIV-2 is Rare type of HIV but results in AIDS as well.
  • 13. A rwa M. A min Body fluids with High HIV Concentration • Blood • Semen (seminal fluids) • Anal secretions • Vaginal secretion • Breast Milk Some body fluids have High concentration of HIV • These fluids have ↑↑ Chances of HIV infection transmission.
  • 14. A rwa M. A min Body fluids with Low HIV Concentration • Saliva • Tears • Urine • Sweat Some body fluids have Low concentration of HIV • Transmission of the infection through these fluids is unlikely If Blood or open wounds are present with these fluids, there are chances of HIV transmission.
  • 15. A rwa M. A min Transmission Routes of HIV Infection • Un-protected sex with HIV infected person. • Sexual Abuse (e.g. Rape) • Sharing contaminated Needles (e.g. Tattoo or piercing needles), syringes, blades or sharp equipment. • HIV can live in used needle up to 42 days depending on Temperature & other factors. HIV can be Transmitted by ..? Most Likely Routes
  • 16. A rwa M. A min Transmission Routes of HIV Infection • Blood Transfusion or Blood products contaminated with HIV. • Organ or Tissue transplant contaminated with HIV. • However, there is low risk of this transmission route because organ donors go under extensive investigations and testing. • IV drug abuse. HIV can be Transmitted by ..? Most Likely Routes
  • 17. A rwa M. A min Transmission Routes of HIV Infection • Mother-to-child-transmission (MTCT) which is the transmission of HIV from the mother to the child during Pregnancy, Delivery or Breastfeeding. HIV can be Transmitted by ..? Most likely Routes
  • 18. A rwa M. A min Transmission Routes of HIV Infection • Eating food pre-chewed by HIV infected person. • If dental/gum wound is present in the HIV infected person and the person who re-chewed the pre- chewed food. • Bitten (with skin break) by HIV infected person. • Contact of wound (Broken skin) with HIV infected blood or fluids. • open-mouth kissing if sores or bleeding gums are present. HIV can be Transmitted by ..? Less Likely Routes
  • 19. A rwa M. A min Transmission Routes of HIV Infection HIV is Not Transmitted by ..? • Hugging, social kissing* or holding hands • Sharing swimming pool • Sharing Toilets seats • Sharing food utensils • Mosquito or Insects bites *Social Kissing: Closed mouth kissing
  • 20. A rwa M. A min HIV Transmission: High Risk Populations • Homosexual Men (Gay) and Bisexual Men. • IV Drug abusers. • Young People (20 – 29 ) years old. • HIV negative Spouse of HIV positive person. • New-born Babies of HIV Mother. • Women working in sex. • Health-care workers (risk of being accidently wounded by HIV contaminated needles or sharp objects). • Researchers working with HIV biosamples.
  • 21. A rwa M. A min HIV Transmission: High Risk Populations This pie chart shows new HIV diagnoses in the United States in 2016 by transmission category Figure source: CDC, Statistics center, HIV in the United States: At A Glance, https://www.cdc.gov/hiv/statistics/overview/ataglance.h tml
  • 22. A rwa M. A min Pathogenesis of HIV: HIV Structure
  • 23. A rwa M. A min Pathogenesis of HIV: HIV Structure
  • 24. A rwa M. A min Pathogenesis of HIV: HIV Life cycle HIV Life Cycle involves Seven steps where HIV uses the machinery of CD4 cells to multiply and spread through the body: 1.Binding 2.Fusion 3.Reverse Transcription 4.Integration 5.Replication 6.Assembly 7.Budding FigureSource:HIVLifeCycle, https://aidsinfo.nih.gov/understanding -hiv-aids/fact-sheets/19/73/the-hiv- life-cycle
  • 25. A rwa M. A min Pathogenesis of HIV 1.Binding Figure Source: Adapted & Modified; HIV Life Cycle, https://aidsinfo.nih.gov/understanding-hiv-aids/fact- sheets/19/73/the-hiv-life-cycle
  • 26. A rwa M. A min Pathogenesis of HIV: HIV Life cycle HIV Life Cycle involves Seven steps where HIV uses the machinery of CD4 cells to multiply and spread through the body: 1.Binding 2.Fusion 3.Reverse Transcription 4.Integration 5.Replication 6.Assembly 7.Budding FigureSource:HIVLifeCycle, https://aidsinfo.nih.gov/understanding -hiv-aids/fact-sheets/19/73/the-hiv- life-cycle
  • 27. A rwa M. A min Pathogenesis of HIV 2. Fusion Figure Source: Adapted & Modified; HIV Life Cycle, https://aidsinfo.nih.gov/understanding-hiv-aids/fact- sheets/19/73/the-hiv-life-cycle
  • 28. A rwa M. A min Pathogenesis of HIV: HIV Life cycle HIV Life Cycle involves Seven steps where HIV uses the machinery of CD4 cells to multiply and spread through the body: 1.Binding 2.Fusion 3.Reverse Transcription 4.Integration 5.Replication 6.Assembly 7.Budding FigureSource:HIVLifeCycle, https://aidsinfo.nih.gov/understanding -hiv-aids/fact-sheets/19/73/the-hiv- life-cycle
  • 29. A rwa M. A min Pathogenesis of HIV 3. Reverse Transcription Figure Source: Adapted & Modified; HIV Life Cycle, https://aidsinfo.nih.gov/understanding-hiv-aids/fact- sheets/19/73/the-hiv-life-cycle
  • 30. A rwa M. A min Pathogenesis of HIV: HIV Life cycle HIV Life Cycle involves Seven steps where HIV uses the machinery of CD4 cells to multiply and spread through the body: 1.Binding 2.Fusion 3.Reverse Transcription 4.Integration 5.Replication 6.Assembly 7.Budding FigureSource:HIVLifeCycle, https://aidsinfo.nih.gov/understanding -hiv-aids/fact-sheets/19/73/the-hiv- life-cycle
  • 31. A rwa M. A min Pathogenesis of HIV 4. Integration Figure Source: Adapted & Modified; HIV Life Cycle, https://aidsinfo.nih.gov/understanding -hiv-aids/fact-sheets/19/73/the-hiv- life-cycle
  • 32. A rwa M. A min Pathogenesis of HIV: HIV Life cycle HIV Life Cycle involves Seven steps where HIV uses the machinery of CD4 cells to multiply and spread through the body: 1.Binding 2.Fusion 3.Reverse Transcription 4.Integration 5.Replication 6.Assembly 7.Budding FigureSource:HIVLifeCycle, https://aidsinfo.nih.gov/understanding -hiv-aids/fact-sheets/19/73/the-hiv- life-cycle
  • 33. A rwa M. A min Pathogenesis of HIV 5. Replication Figure Source: Adapted & Modified; HIV Life Cycle, https://aidsinfo.nih.gov/understanding-hiv-aids/fact-sheets/19/73/the- hiv-life-cycle
  • 34. A rwa M. A min Pathogenesis of HIV: HIV Life cycle HIV Life Cycle involves Seven steps where HIV uses the machinery of CD4 cells to multiply and spread through the body: 1.Binding 2.Fusion 3.Reverse Transcription 4.Integration 5.Replication 6.Assembly 7.Budding FigureSource:HIVLifeCycle, https://aidsinfo.nih.gov/understanding -hiv-aids/fact-sheets/19/73/the-hiv- life-cycle
  • 35. A rwa M. A min Pathogenesis of HIV 6. Assembly Figure Source: Adapted & Modified; HIV Life Cycle, https://aidsinfo.nih.gov/understanding-hiv-aids/fact-sheets/19/73/the- hiv-life-cycle
  • 36. A rwa M. A min Pathogenesis of HIV: HIV Life cycle HIV Life Cycle involves Seven steps where HIV uses the machinery of CD4 cells to multiply and spread through the body: 1.Binding 2.Fusion 3.Reverse Transcription 4.Integration 5.Replication 6.Assembly 7.Budding FigureSource:HIVLifeCycle, https://aidsinfo.nih.gov/understanding -hiv-aids/fact-sheets/19/73/the-hiv- life-cycle
  • 37. A rwa M. A min Pathogenesis of HIV 7. Budding Figure Source: Adapted & Modified; HIV Life Cycle, https://aidsinfo.nih.gov/understanding-hiv-aids/fact-sheets/19/73/the- hiv-life-cycle
  • 38. A rwa M. A min Pathogenesis of HIV: HIV Life cycle HIV Life Cycle involves Seven steps where HIV uses the machinery of CD4 cells to multiply and spread through the body: 1.Binding 2.Fusion 3.Reverse Transcription 4.Integration 5.Replication 6.Assembly 7.Budding FigureSource:HIVLifeCycle, https://aidsinfo.nih.gov/understanding -hiv-aids/fact-sheets/19/73/the-hiv- life-cycle
  • 39. A rwa M. A min Complications of HIV Infection • Death: ↑↑ Morbidity & ↑↑ Mortality • HIV infected patients face death due to opportunistic Infections, severe CNS conditions and infections- related-cancers. • CNS Conditions occur when HIV enters the CNS and cause complications such as: • HIV Encephalopathy • AIDS Dementia complex • HIV-associated Progressive Encephalopathy (HPE)
  • 40. A rwa M. A min HIV Diagnosis: laboratory Tests • ELISA TEST  Tests HIV Antibodies NOT HIV  Samples: Blood, Serum, Plasma, Saliva, Urine  Tests 2 – 8 weeks after infection  Infected person can be Negative between few weeks to few months after infection.  If ELISA results showed HIV-Positive results, Western blot Cross check should be done to confirm the results.  If Western blot cross check showed HIV-Positive results → HIV infection is confirmed. ELISA: enzyme-linked immunosorbent assay (ELISA)
  • 41. A rwa M. A min HIV Diagnosis: laboratory Tests Quick HIV Diagnosis Tests • Rapid HIV Antibodies Test  Rapid & Easy to perform test for HIV Antibodies  Detection within 30 minutes.  Sample: Finger prick Blood. • OraQuick  FDA-approved oral swab in-home test for HIV-1 and HIV-2.  Sample: Oral swab.  Rapid home test to test HIV Antibodies.  Can be done in 20 minutes.  If Positive results, it should be confirmed by Blood test
  • 42. A rwa M. A min HIV Diagnosis: laboratory Tests Viral Load Test (VLT) Measures the amount of HIV-RNA in blood (amount of HIV in blood). Number of copies of HIV-RNA in a milliliter of blood. Can be tested 1 – 4 weeks from HIV Exposure. Should be used in the evaluation of the efficacy of ART. Viral Load should fall within 3 – 6 months of Treatment. ART: Antiretroviral Therapy
  • 43. A rwa M. A min HIV Diagnosis: laboratory Tests Viral Load Test (VLT) What does ↑↑ Viral Load Number indicate? ↑↑ HIV amount in Blood ↑↑ Fast Damage of CD4 cells (CD4 Cell count will fall) ↑↑ Risk of Developing AIDS & Death. Patient may Not be taking his ART medications. Patient is Not responding well to ART. ART: Antiretroviral Therapy
  • 44. A rwa M. A min HIV Diagnosis: Laboratory Tests • CD4 cell counts: Since HIV destroys CD4 Cells, the count of CD4 cells is important biomarker to assess:  State of patient’s Immune system  HIV disease progression  Efficacy of HIV Therapy Normal blood values for CD4 cells is (500–1500 cells/mm3). Should be measured every 3 – 6 months in the First 2 years of HIV infection.
  • 45. A rwa M. A min HIV Diagnosis: Laboratory Tests CD4 cell counts What does ↓↓ CD4 Cell counts indicate? ↑↑ Damage of CD4 cells. ↑↑ Risk of Developing AIDS & Death. Patient may Not be taking his ART medications. Patient is Not responding well to ART. ART: Antiretroviral Therapy
  • 46. A rwa M. A min Upon contracting HIV infection, infected person doesn’t have signs which indicate the infection. However, while signs are absent, infection continues to damage CD4 Cells and immune system. Stages of HIV Infection Acute HIV Infection •Flu-Like symptoms •Lasts for 2 – 4 weeks of contracting HIV infection AIDS •CD4 Cell counts below 200 cells/mm3 •↑↑ Risk of Opportunistic Infections Chronic HIV Infection (Clinical Latency) • Chronic HIV Infection after Acute phase • Can last for decade (≈ or > 10 years) HIV Infection has Three Main stages
  • 47. A rwa M. A minFigure source: https://commons.wikimedia.org/wiki/File:Hiv-timecourse_copy.svg
  • 48. A rwa M. A min Figure source: The Stages of HIV Infection, https://aidsinfo.nih.gov/understanding-hiv-aids/fact-sheets/19/46/the-stages-of-hiv-infection
  • 49. A rwa M. A min HIV Diagnosis: Symptoms of Acute HIV Infection • Flu-like symptoms • High fever • Sore throat • Headache • Lymphadenopathy • Stomach up set, Nausea, Vomiting & Diarrhea • Skin rashes • Joints pain • Muscle pain • Tiredness, Malaise & Fatigue • Weight Loss • Liver & Spleen Enlargement •Acute HIV Infection symptoms are relatively Non-specific. •HIV AB Test often Negative, however, becomes Positive within 3 – 6 Months. AB: Antibodies
  • 50. A rwa M. A min HIV Diagnosis: Clinical Manifestations of Acute HIV Infection
  • 51. A rwa M. A min HIV Diagnosis: Clinical Manifestations of Chronic HIV Infection •Chronic HIV Infection (Clinical Latency) is Asymptomatic stage i.e. Free of Symptoms. •HIV is growing very slowly. •HIV Anti-Bodies are detectable in blood (Positive). •HIV level in blood may drop to Low Levels, but PATIENT still can SPREAD HIV to OTHERS. •There might be swollen glands. •How long does the HIV Clinical Latency take? •It depends on the Patient’s immunity & HIV treatment.
  • 52. A rwa M. A min HIV Diagnosis: AIDS Clinical Manifestations • AIDS is the third and Symptomatic stage of HIV where patient is at very high risk of contracting Opportunistic Infections. • CD4 Count in AIDS patient < 200/mm3 • Patient will have symptoms such as:  Rapid weight Loss • Respiratory signs & symptoms  SOB & Cough • GI symptoms  Chronic Diarrhea, Nausea & Vomiting • Skin  Skin Lesions  Poor wound healing  Excessive sweating
  • 53. A rwa M. A min Figure Source: Nursing Education Consultant, https://www.pinterest.dk/pin/13440437 0106704850/visual- search/?x=16&y=12&w=530&h=398 Clinical Manifestations of AIDS
  • 54. A rwa M. A min Management of HIV HIV is NOT CURABLE. Goals of HIV Therapy are: Improving patient’s quality of life. Reducing Morbidity and Mortality. Restoring patient’s CD4 cell counts. Preventing HIV replication  Reducing HIV Viral Load to undetectable level (<50 copies/mL). Preventing and treating opportunistic infections. Preventing HIV transmission from infected subjects.
  • 55. A rwa M. A min Management of HIV Non-Pharmacological Treatment of HIV:  Patient Education  Providing Social Support to the patient  Regular Exercising  Adequate rest  Avoiding Alcohol Drinking  Smoking Cessation  Eating healthy and Nutritious Diet
  • 56. A rwa M. A min Management of HIV: Pharmacological Management HIV Pharmacological Treatment:  HIV Pharmacological treatment is achieved by using Antiretroviral Therapy (ART).  ART is evolving quickly.  More than 30 Antiretroviral drugs.  ART consists of combination of three HIV antiretroviral drugs from Two pharmacological Classes.
  • 57. A rwa M. A min Management of HIV: Pharmacological Management Benefits of using ART: Preventing HIV from replication. ART Combination attacks HIV life cycle at different steps. Synergistic effect ↑↑ CD4 cell counts. ↓↓ Risk of HIV-Drug-resistance strains development. ↓↓ side-effects of high doses of ART drugs (↓↓ Drug Toxicity) ↓↓ HIV transmission
  • 58. A rwa M. A min Management of HIV: Pharmacological Management Main Aim of ART CD4Counts ViralLoad ART ART: Antiretroviral Therapy
  • 59. A rwa M. A min Management of HIV: Pharmacological Management When to Initiate ART in HIV infected subjects? DHHS Guidelines of ART* use (2017): ART is recommended for all individuals with HIV, regardless of CD4 cell counts to reduce morbidity, mortality and to prevent transmission. *DHHS Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV, 2017, available at https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv/0
  • 60. A rwa M. A min Management of HIV: Pharmacological Management Main Classes of HIV Antiretroviral Drugs:  Entry inhibitors; e.g. Enfuvirtide  Reverse transcriptase inhibitors NRTIs: e.g. Tenofovir, Emtricitabine (Truvada®: Tenofovir/Emtricitabine) NNRTIs: e.g. Efavirenz, Nevirapine  Integrase strand transfer inhibitors (InSTIs); Raltegravir, Dolutegravir  HIV protease inhibitors (PIs); e.g. Darunavir, Ritonavir, Atazanavir, NRTIs: Nucleoside reverse transcriptase inhibitors, NNRTIs: Non-nucleoside reverse transcriptase inhibitors
  • 61. A rwa M. A min Management of HIV: Pharmacological Treatment Examples of ART Combinations Examples of ART Combinations • HIV-PI based: Darunavir + Ritonavir + Tenofovir + Emtricitabine • InSTI based: Raltegravir + Tenofovir + Emtricitabine Preferred Combinations • NNRTI based: Efavirenz + Tenofovir + Emtricitabine • HIV-PI based: Atazanavir + Ritonavir + Tenofovir + Emtricitabine Alternative Combinations InSTIs: Integrase strand Transfer Inhibitor, NNRTI: Non-nucleoside reverse transcriptase inhibitor, PI: Protease Inhibitor
  • 62. A rwa M. A min Common Side effects of HIV Antiretroviral Drugs Table source: The potential anesthetic threats, challenges and intensive care considerations in patients with HIV infection, http://www.jpbsonline.org/viewimage.asp?img=JPharmBioallSci_2013_5_1_10_106554_b3.jpg
  • 63. A rwa M. A min Management of HIV in Pregnancy • HIV infected women should be treated regardless of pregnancy status. • ART for pregnant HIV positive woman is Not contraindicated. • ART can reduce Perinatal Transmission. • Safety, Efficacy, and Pharmacokinetic (PK) data of antiretroviral drugs should be considered when designing the ART combination in Pregnancy. • E.g. of Preferred ART Combination in Pregnancy:  Two NRTI: Tenofovir + Emtricitabine  Two PIs: Darunavir + Ritonavir ART: Antiretroviral Therapy, NRTIs: Nucleoside reverse transcriptase inhibitor, PIs: Protease Inhibitor
  • 64. A rwa M. A min Management of HIV: Monitoring of ART Plasma HIV-RNA levels (Viral Load) and CD4 cell counts periodical measurement is necessary: • To determine when to initiate or modify antiretroviral treatment regimens. • To determine HIV disease progression.
  • 65. A rwa M. A min HIV Prevention • There is NO Vaccination for preventing HIV. • Prevent Sexual HIV Transmission  Abstinence and Marital Fidelity are the best way to prevent sexual HIV transmission.  Ensure Pre-marital HIV Testing  Ensure mutual Non-HIV infected marriage  Condom use ↓↓ HIV transmission by approximately 80%.  Male circumcision ↓↓ transmission risk in circumcised Men. • Avoid IV Drug abuse.
  • 66. A rwa M. A min HIV Prevention • Educating the public on the prevention of HIV. • Ensure proper HIV testing of Blood products / transplants and safe blood transfusion. • Prevent Mother-to-Child-transmission of HIV. • Ensure Proper Hygiene and using sterile personal sharp objects (Needles & Blades). • Avoid sharing Needles or Sharp objects e.g. Blades, shavings, needles, razors • Prevent HIV transmission in Healthcare settings.
  • 67. A rwa M. A min •*Proper Sterilization of Surgical and Dental equipment. Preventing HIV Transmission in Health- Care Setting Figure Source: https://www.pinterest.co.uk/pi n/320600067194445053/
  • 68. A rwa M. A min