16 - Intro to HIV/AIDS Flashcards
HIV-UNinfected / Normal Count
CD4+ T-cell Count
500-1500 cells/mm3
>500 = Lower risk of infections
Below Normal - CD4+ T-cell Count
200-500 cells/mm3
May be at HIGHER RISK of
Opportunistic Infections or Health Problems
Low CD4+ T-cell Count
< 200 cells/mm3
AIDS
<14% of total t-cell count
HIV vs AIDS
HIV initially causes HIV disease
As it progresses…
HIV CAUSES AIDS
Aids is defined as:
- *CD4 T-Cell # <200** cells/mm3
- *OR**
- *Diagnosis of 1 of the AIDS-defining Conditions**
AIDS-Defining Conditions
Can be aids if it has one of these
OR
CD4 T-cell count <200 cells/mm3
Bacterial Infections
Candidiasis
of Bronchi / Trachea / Esophagusor Lungs
Herpes Simplex
Chronic ulcers / bronchitis / pneumonitis / esophagitis
Histoplasmosis
Mycobacterium Avium Complex
Pneumocytis Jirovecii Pneumonia
Toxoplasmosis of Brain
OTHER Factors that can Impact
CD4 T-Cell Count
LAB VARIATION
CD4 VARIES OFTEN –> LOOK AT HIV VIRAL LOAD
Medications
Chemo / Interferon / Transplant Meds / Steroids
Disease States
Splenectomy / C-inf w/ HTLV-1 / Hep Bor C
Acute Infections
Sress / Common Cold / Viral - Bacterial Illness
Risk Factors for:
HIV TRANSMISSION
Bodily Fluids
Blood / semen / vaginal / breast milk
Unprotected Sex
IV Drug Use
Mother - Child
Needle STICK
7 Steps of HIV-1 Lifecycle
Binding
HIV gp120 subunit –> CD4 Tcell
Fusion
HIV virion + CD4 membrane fuse
- *Reverse Transcription**
- *RT** converts HIV RNA –> HIV DNA
- *Integration**
- *Integrase** INSERTS HIV DNA –> Nucleus
Transcription & Translation
Using CD4 T-cell proteins –> HIV protein Copies
- *Assembly**
- *PROTEASE** –> creates new virus components
Budding
HIV virus exits cell, CD4 lysis
Which of the 2-step Tests for confirming HIV?
Highly SENSITIVE
if HIV is present –> test will be REACTIVE
Possible for a FALSE POSITIVE
RARE but sometimes performed test
SCREENING TESTS
If NEGATIVE –> NO confirmatory test is needed
Which of the 2-step Tests for confirming HIV?
HIGH SPECIFICITY
if reactive –> HIV is present
CONFIRMATION TESTS
Performed if:
at LEAST 1 SCREENING TEST is Reactive
FDA Approved Tests for HIV Diagnosis:
Specimen Types
For PREP:
Whole Blood or Plasma/Serum
Also available:
Oral Fluid
HISTORY
of HIV Testing
Early Generations = 1st - 3rd
ANTIBODY DETECTION
Western Blot -> HIV-1 ELISA / HIV-2 ELISA
~50 - 40 - 20 days
- *Newer Generations = 4th / 5th**
- *VIRAL+AB DETECTION**
- *HIV-1 p24 ANTIGEN** + Both ELISA’s
- *WINDOW PERIOD TO 10 DAYS**
Generalized GRAPH / COURSE
of UNTREATED HIV INFECTION
Primary/Acute Infection = Stage 1
Large amuonts of virus being produced –> significant decline in CD4
Many develop = WORST FLU EVER
Chronic/Clinical Latency = Stage 2/3
HIV is active but produces VERY LOW LEVELS
May be ASYMPTOMATIC, w/o treatment - ~10 year avg
AIDS = Stage 3/4
CD4 cells < 200 cell/mm3
w/o treatment - ~3 year SURVIVAL average
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Clinical Symptoms of
ACUTE HIV INFXN
Weeks 0-12 - rapidly producing HIV virus
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“WORST FLU EVER”
What is TESTED FOR for HIV diagnosing?
VIRAL RNA
shown FIRST, steady level throughout
HIV-1 p24 Antigen
shown next, declines
HIV ANTIBODY
shown last, but rises over time
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Benefits of EARLY THERAPY
↓Deaths / ↓AIDS-releated Illness
↓non-AIDS conditions
Preservation of Immune fxn and Enhanced Recovery to
CD4 # > 800 cells /mm3
REDUCTION IN RISK OF HIV TRANSMISSION
Early Therapy / Younger –> better CD4 improvement
What is ART?
Anti-Retro-Viral THERAPY
Combines:
at least 3 Active ARVs (AntiRetroViral) from
2 Different Classes
Each ARV class interferes with HIV replication at: **different stages of HIV life cycle**
resistance genotype is drawn before starting
Typical ART for:
Treatment-NAIVE Patients
2 NRTI
Nucleoside RT Inhibitors
+PLUS+
- *1 OTHER**
- *INSTI / NNRTI / PI**
or
a Single Regimen Tablet = Combo of above
Where ARVs attack in the HIV Cycle
Anti-Retro-Virals
1) Entry Inhibitors
2) Fusion Inhibitors
3) NRTIs // NNRTIs
Nucleoside RT inhibitors
4) INSTIs
Integrase Strand Transfer Inhibitors
5) none for Transcription/Translation
6) Protease Inhibitors & Boosters
7) none for budding
Goals of HIV THERAPY
Suppress plasma HIV RNA
Maintain a undetectable viral load by suppressing viral replication
12-24 weeks
Restore/preserve Immune Fxn
Increase CD4 Count 50-150 cells/mm3 PER YEAR
until steady level achieved
REDUCE HIV-associated morbidity
prolong durations & quality of survival
PREVENT HIV TRANSMISSION
Why is ADHERENCE to ARTIs ESSENTIAL?
STRICT adherence has been reported to:
↑Sustained virologic Control
↑Overall health & survival
↓Risk of Transmission
Suboptimal adherence has been reported to:
↓Virologic Control
↑Morbidity/Mortality
↑Risk of DRUG RESISTANCE –> limiting effectiveness