HIV - Virology & Clinical Flashcards
What activities allow HIV transmission? [6]
- Anal or vaginal intercourse → HIGH-RISK
- Unprotected sexual contact
- In the genitals and rectum, HIV may infect the mucous membranes directly or enter through cuts and sores caused during intercourse (many of which would be unnoticed)
- Oral sex (mouth-penis, mouth-vagina) → LOW-RISK
- Direct blood contact, including injection drug needles & sharing equipment or certain blood products
- Transmission in healthcare settings (accidents)
- Transmission via donated blood or blood clotting factors (blood transfusions)
- Mother-to-child transmission (before/during birth, or through breast milk)
Describe the pathophysiology of how HIV causes infection [8]
- HIV infects cells in the immune system such as T helper cells, macrophages and dendritic cells
- All these cells carry CD4 receptors which allow HIV entry
- HIV infection causes depletion of CD4 T helper cells by:
- Direct viral killing of cells
- Apoptosis of uninfected “bystander cells”
- CD8+ cytotoxic T cell killing of infected CD4+ cells
- Abnormal B cell activation resulting in excess/inappropriate immunoglobulin production
- Once CD4+ cells fall below a critical level (≤ 200), the person is at risk of opportunistic infections and some cancers
Define latency in terms of HIV [1]
the term used to describe the long asymptomatic period between initial infection and advanced HIV (AIDS)
What are the 5 classes of drugs used in highly active anti-retroviral therapy (HAART) and how is it usually administered? [7]
- Nucleoside reverse transcriptase inhibitors (NRTIs)
- Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
- Integrase strand transfer inhibitors (INSTIs)
- Protease inhibitors (PIs)
- CCR5 antagonists (also known as Fusion inhibitors/R5 inhibitor)
- Usually given as a triple therapy
- 2 Nucleoside Reverse Transcriptase Inhibitors + 1 drug from another class
- Combination pills available
What is the mechanism of action of fusion inhibitor/R5 inhibitor? [1]
inhibit the entry of the virus into the cell by blocking the CCR5 co-receptor
What is the mechanism of action of NRTIs and NNRTIs? [1]
inhibit reverse transcriptase and the conversion of viral RNA into DNA
What is the mechanism of action of integrase inhibitors? [1]
inhibit integrase and prevent HIV DNA integrating into the nucleus
What is the mechanism of action of protease inhibitors? [1]
inhibit protease, an enzyme involved in the maturation of virus particles
What are the short-term side effects of ART? [9]
- Rash
- Hypersensitivity (Abacavir and Nevirapine)
- CNS side effects (Efavirenz)
- Sleep disturbance
- Vivid dreams
- Mood changes
- GI side effects
- Renal
- Hepatic
What are the long-term side effects of ART? [7]
- Body shape changes
- Lipoatrophy/lipodystrophy
- Weight gain
- Renal (Tenofovir disoproxil)
- Hepatic
- Lipid
- Bone
What population groups are at high risk of developing HIV? [5]
- Sub Saharan Africa
- esp. Southern Africa
- Men who have male sexual partners
- Children of people living with HIV
- People who inject drugs
- People who have transactional sex
List the symptoms of acute HIV “seroconversion” under the following headings:
- systemic [2]
- central [3]
- nose/mouth [3]
- oesophagus [1]
- lymph nodes [1]
- muscles [1]
- gastric [2]
- liver & spleen [1]
- skin [1]
- Systemic
- Fever
- Weight loss
- Central
- Malaise
- Headache
- Neuropathy
- Nose/mouth:
- Pharyngitis
- Sores
- Thrush
- Oesophagus
- Sores
- Lymph nodes
- Lymphadenopathy
- Muscles
- Myalgia
- Gastric
- Nausea
- Vomiting
- Liver and spleen
- Enlargement
- Skin
- Rash
What are the differential diagnosis for primary HIV infection? [5]
- Infectious mononucleosis
- Secondary syphilis
- Sexually transmitted disease
- Drug rash
- Other viral infections
- e.g. CMV, influenza
What are the 2 blood markers used for HIV? [2]
- HIV viral load
- undetectable = under 200 copies/ml
- CD4
- Calculated from total lymphocyte count
- HIV-negative: 400-1600 per mm3
Name and describe the 5 clinical stages in the natural history of HIV [11]
- Primary Infection
- When first acquiring primary infection, acute HIV syndrome ensues and as the HIV viral load rapidly increases, the CD4 count rapidly drops.
- This is due to wide dissemination of the virus and seeding of the lymphoid organs
- This is the period when you would typically seen symptoms of HIV seroconversion
- Clinical Latency
- Later, a period of clinical latency develops, when the HIV viral load plateaus, but the CD4 count continues to decrease (after increasing slightly at the start of the latency period)
- Constitutional symptoms
- At the end of the latency period, constitutional symptoms of HIV develop
- Opportunistic disease
- Once the CD4 count drops below 200/mm3, the risk of developing opportunistic diseases increases.
- Death
