HIV/AIDS Flashcards
(19 cards)
What are the risk factors for developing HIV?
- Needle sharing with IV drug use
- Unprotected receptive anal intercourse
- Unprotected receptive penile-vaginal sexual intercourse
- Percutaneous needle stick injury
- High maternal viral load (mother to child transmission)
- Contaminated blood products and organ donations.
How is HIV transmitted?
- Sexual intercourse (vaginal and anal)
- Mother to child - most infections take place perinatally or via breast milk
- contaminated blood, blood products and organ donations.
- contaminated needles
What are the common opportunistic pulmonary infections from which a patient with AIDS may suffer?
• Pulmonary:
- Pnuemocystis jiroveci pneumonia
- Pyogenic bacteria
- M. tuberculosis
What are the common opportunistic gut infections from which a patient with AIDS may suffer?
- Candidiasis
- HSV
- CMV
- Ahthous ulcers
- Salmonella
- Shigella
- Campylobacter
- Atypical mycobacteria
- C.difficile
What are the common opportunistic eye infections from which a patient with AIDS may suffer?
CMV retinitis
What are the common opportunistic neurological infections from which a patient with AIDS may suffer?
- Acute HIV: is associated with transient meningoencephalitis, myelopathy, and neuropathy
- Chronic HIV: associated neurocognitive disorder (hand): comprises dementia and various encephalopathies
Toxoplasma gondii: is the main CNS pathogen in aids.
What are the 2 types of HIV?
HIV-1 and HIV-2
What type of HIV is more common?
HIV-1
What is the structure of HIV?
• Physical structure: icosahedral with a spiked envelope
• Genome (HIV is aretrovirus, meaning that itsgenome is stored in the form ofRNA(rather thanDNA): 9 genes encoding a total of 15 proteins (e.g. reverse transcriptase (Required to convert viralRNA toDNA), integrase (Required to insert the viralgenes into the hostgenome) and envelope proteins (The two major envelopeproteinaregp120andgp41. They help attach the virus to the host).
○ Pol genes codes for gag protein, which consist of matrix protein, nucleocapsids, and capsid proteins.
Env gene codes for surface glycoproteins, gp41 and gp120
Why is HIV difficult to treat using antiviral drugs?
The rapid emergence of viral quasi-species (closely related but genetically distinct variants) is due to the high mutation rate of reverse transcriptase and the high rate of viral turnover. This genetic diversification has implications for the evolution of viral variants with resistance to antiviral drugs.
How does HIV enter cells?
HIV surface glycoprotein gp120 binds to the CD4 molecule on host lymphocytes and other cells bearing the CD4 receptor. The interaction between CD4 and HIV surface glycoprotein together with host chemokine co-receptors CCR5 and CXCR4 is responsible for HIV entry into cells and release of viral RNA.
Why are people with HIV more susceptible to infections?
There is a progressive and severe depletion of infected CD4 helper lymphocytes, which results in host susceptibility to infections with intracellular bacteria and mycobacteria. The coexisting antibody abnormalities predispose to infections with capsulated bacteria, e.g. Streptococcus pneumoniae and Haemophilus influenzae. The clinical illness associated with HIV infection is due to this immune dysfunction, and also to a direct effect of HIV on certain tissues.
What are the modifiable risk factors associated with HIV?
- Viral load: studies have shown that transmission is unlikely if viral load is <400 copies/ml (HIV concentration is higher in male ejaculate than in vaginal secretions).
- Circumcision: reduced risk of infection for circumcised men (Circumcision results in cornification of thepenisglans, thus reducing the likelihood of lesions during intercourse.)
- Coinfection: genital inflammation (e.g. as a result of coinfection with other pathogens such as HPV or genital herpes) increases local virus concentration and therefore risk of transmission - Genital mucosal damage: increases risk of transmission
Describe the characteristics of acute HIV infection/acute retroviral syndrome?
• Also referred to as acute retroviral syndrome (ARS) or described as a mononucleosis-like syndrome (Acute retroviral syndrome occurs only in about half of all patients. Severe neurological deficits are possible but rare at this stage. Rashes and diarrhoea are more common in untreated acute HIV infection than ininfectious mononucleosis.
• Fever
• Fatigue
• Myalgia and arthralgia
• Headache
• Generalized nontender lymphadenopathy (usually develops in the second week after infection).
• Generalized rash (Oftenmaculopapular, but appearance is variable. Usually develops on the2ndor3rddayafter infection and lasts for5–8 days.)
Oropharyngeal symptoms (sore throat, ulcerations, painful swallowing)
Describe the process of initial infection and HIV replication cycle?
- HIV enters the body (e.g. via mucosal lesions or via infection of mucosal/cutaneous immune cells), then attaches to the CD4 receptor on target cells with its gp120 glycoprotein (binding)
• Cells that have CD4 receptors: T lymphocytes (e.g. T helper cells), macrophages, monocytes, dendritic cells (CNS).- Viral envelope fuses with host cell, capsid enters the cell
• For fusion, CD4 receptor and a coreceptor (CCR5 in macrophages, and CCR5 or CXCR4 in T cells) must be present.
• Patients without CCR5 receptors appear to be resistant to HIV, those patients either have a homozygous CCR5 mutation (substantial resistance) or a heterozygous CCR5 mutation (slower course). - Virion’s RNA is transcribed into DNA (by the viral reverse transcriptase) and then integrated into the host’s DNA (by the viral integrase)
- Viral DNA is replicated and virions are assembled
Virion repurposes a portion of the cell’s membrane as envelope and leaves the cell (budding) –> cell death (The exact mechanisms which leads to cell death by the HIV replication cycle is not yet fully understood).
- Viral envelope fuses with host cell, capsid enters the cell
How does WHO classify HIV?
- Primary HIV infection: acute retroviral syndrome or asymptomatic
- Clinical stage 1: persistent generalized lymphadenopathy (PGL) or asymptomatic
- Clinical stage 2: e.g. unexplained moderate weight loss (< 10%), recurrent fungal/viral/bacterial infections - Particularly of theoral cavityand the respiratory tract
- Clinical stage 3: e.g., unexplained weight loss (>10%) unexplained chronic diarrhoea (>1 month), unexplained persistent fever (≥38.7 degrees celsius intermittent or constant >1 month), persistent/severe fungal/viral/bacterial infections - particularly of the oral cavity and of the respiratory tract, unexplained anaemia (<8g/dL) and/or neutropenia (<500 cells/µL) and/or chronic thrombocytopenia (<50,000/µL) for more than 1 month.
- Clinical stage 4: AIDS-defining conditions (e.g. kaposi sarcoma)
What are the screening tests of HIV?
○ Combination antigen/antibody test (first choice screening test): Detect both HIV antigen (p24) and anti-HIV antibodies –> a negative result essentially rules out HIV infections (almost 100% sensitivity)
○ Antibody-only tests:
1. ELISA (enzyme-linked immunosorbent assay): standard method for detecting antibodies within approx. 1-3 hours; requires laboratory.
2. Rapid tests: can deliver results in ~ 20 minutes and does not require a laboratory, which makes them suitable as an alternative to the more complex tests in some out patient settings (however, less reliable than ELISA).
What are the tests used to confirm a diagnosis of HIV?
- HIV-1/HIV-2 antibody differentiation immunoassay (first choice confirmatory assay): can detect both HIV-1 and HIV-2 in ~ 20 minutes and distinguishes between the two types.
- Western blot: tests may be negative up to 2 months after infection; results are usually available after several days and HIV subtype O is not reliably detected.
What is done for post-treatment monitoring?
- Viral RNA load: indicator of ART response
- Decrease in viral load indicates effective treatment
- Prognostic marker in long-term treatment (Higher viral load →↑ destructionofCD4+ lymphocytes → more severeimmunodeficiency → worse prognosis - CD4+ count: correlates with overall immune function (measured using flow cytometry via marked antibodies)
- CD4+ counts increase in response to successful ART therapy
- Critical measurement for initiating opportunistic infection prophylaxis - CD4+:CD8+ ratio: Used in the immunological evaluation of long-term follow up cases.
- Expected increase in ratio within successful ART therapy
- Correlates with immune dysfunction and viral reservoir size.
