AIDS Flashcards
Pathophysiology of AIDS
- AIDS is caused by HIV
- HIV is a retrovirus
- These carry genetic material (RNA) - HIV consists of a viral core containing RNA, surrounded by an envelope consisting of protruding glycoproteins
- HIV targets CD4 receptors on the surface of T lymphocytes and the chemokine receptor CCR5 or CXCR4
HIV Life Cycle: Attachment
- Glycoproteins of HIV bind with host’s uninfected CD4+
- Results in fusion of HIV with CD4+ T-cell membrane
HIV Life Cycle: Uncoating
Contents of HIV viral core empties into CD4+ cell
HIV Life Cycle: DNA Synthesis
- HIV changes its genetic material from RNA to DNA through reverse transcriptase
- Results in double-stranded DNA that carries instruction for viral replication
HIV Life Cycle: Integration
- New viral DNA enters the nucleus of CD4+ T-cell, resulting in permanent lifelong infection
- Prior to this step, the person has only been exposed, not infected with HIV
- At the end of this step HIV is PERMANENT
HIV Life Cycle: Transcription
Double stranded DNA forms single stranded RNA (mRNA)
- Builds new virus
HIV Life Cycle: Translation
The mRNA creates chains (polyproteins) that have components needed for new virus construction
HIV Life Cycle: Cleavage
HIV enzyme protease cuts the polyprotein chain into two individual proteins that make up the new virus
HIV Life Cycle: Budding
New proteins and viral RNA migrate to the membrane of the infected CD4+ T-cell, exit from the cell to start the process all over again
Fluids that can transmit HIV infection
- Blood (tranfusion, needles)
- Pre-seminal fluid/semen
- Vaginal fluid
- Amniotic fluid
- Breast milk
HIV can enter the body through:
- Lining of the anus or rectum
- Lining of the vagina and/or cervix
- Opening to the penis
- Mouth that has sores or bleeding gums
- Cuts and sores
- Needle sharing
HIV Prevention
- Male and female condoms
- PEP
- PMTCT
- Male circumcision
- Voluntary counseling and testing
- Clean injecting equipment
- Cervical barriers and vaginal diaphragms
- Microbicides
- PrEP
PrEP
Preventative Exposure Protection
- For high risk groups
Stages of HIV
- Primary Infection
- HIV Asymptomatic Category A
- HIV Asymptomatic Category B
- AIDS: CDC Category C
HIV Primary Infection
- The period from infection to the development of HIV specific antibodies
- The window period is the time during which an HIV positive person test negative on the HIV antibody test
- The patient is still highly infectious
- Viral load is very high during this period
- After 2-3 weeks the disease can be detected, but the antibodies lack the ability to control the virus
HIV Primary Infection is Characterized by:
- High levels of viral replication
- Normal CD4+ count = 500-1500 cells/mm3 of blood
- Widespread dissemination of HIV throughout the body
- Destruction of CD4 T-cell counts
- Dramatic drop in CD4 count
Why is there a dramatic drop in CD4 count during the HIV primary infection stage?
- Individual is responding to the virus
2. Antibody molecules are trying to remove the virus from the body
Viral Set Point
Amount of virus remaining in the body after the initial immune response
- Results in a steady state of infection that last for years - Varies greatly among individuals - The higher the viral set point, the poorer the prognosis
Symptoms of Primary HIV Infection
- Fever
- Lymphadenopathy
- Pharyngitis
- Skin rash
- Myalgias/Arthralgias
- Flu-like symptoms
HIV Asymptomatic: Category A
- CD4+ count > 500
1. Occurs after the viral set point is reached
2. HIV+ individuals enter a chronic state
3. Immune system cannot eliminate the virus, despite its best effort
4. On average, 8-10 years pass before the individual develops an HIV related illness
5. Patients generally feel well, and have few if any symptoms
6. CD4+ counts remain high enough to preserve immune defensive responses
- CD4+ count > 500
HIV Asymptomatic: Category B
- CD4+ count 200-499
1. Over time CD4+ counts fall and the patient becomes ill
2. The condition must:- Be directly caused by HIV infection or defect in cellular immunity
- Must have a clinical course that requires management of a complicated HIV infection
- CD4+ count 200-499
Examples of conditions that are present in HIV Category B
- Candidiasis (thrush)
- Cervical dysplasia
- Cervical carcinoma
- Herpes zoster
- Idiopathic thrombocytopenia purpura
- Peripheral neuropathy
AIDS: CDC Category C
- CD4+ count < 200 cell/mm3
1. Once a patient enters this stage, the individual remains in this category
2. As CD4+ levels drop below 100 the immune system is severely impaired
- CD4+ count < 200 cell/mm3
Examples of conditions associated with ADIS category C
- Mycobacterium tuberculosis
- Invasive cervical carcinoma
- HIV encephalopathy
- Kaposi’s sarcoma
- Wasting syndrome related to HIV
Diagnostic Tests: Monitoring of HIV Infection
- Viral load test
2. CD4+ Count
Viral Load Test
- Measures plasma HIV RNA levels in the blood
- Viral load testing at initial diagnosis and every 3-4 months
- Viral load is a better predictor of the risk of HIV disease progression than CD4+ count
- The lower the viral load, the longer the time until AIDS diagnosis and the longer the survival time
CD4+ Count
- The number of helper T cells per cubic mm of blood
- AIDS patients get CD4+ counts every 3-4 months to assess response to ART or HAART
- One of the key factors in determining both the urgency of antiretroviral therapy (ART) initiation and the need for prophylaxis for opportunistic infections
- It is also the strongest predictor of subsequent disease progression and survival
- Indicator if they need a medication change
ELISA/EIA
Enzyme-linked immunosorbent assay OR enzyme immunoassay
- Identifies antibodies directed specifically against HIV in the blood
- If test is positive, a 2nd test is done to verify the results = Western Blot Assay
Western Blot Assay
Identifies specific antibodies or proteins in blood. The proteins are separated by electrophoresis, transferred to nitrocellulose, and reacted with antibody
** Used to confirm seropositivity when EIA/ELISA result is positive