W8 Clinical aspects of viral infections Flashcards
What is HIV & AIDS?
HIV - is a pandemic infectious disease whose impact on societies is without precedent. It is caused by a retrovirus that infects and replicates in human lymphocytes and macrophages, eroding the integrity of the human immune system over a number of years, culminating in immune
deficiency and a susceptibility to a series of opportunistic and other infections as well as the development of certain malignancies.
AIDS – (a syndrome of a constellation of infections, conditions, or malignancies) occurs as a result of HIV infection, usually after approximately 6 to 9 years of infection.
Pathophysiology of HIV
- Entry into host cells: HIV primarily infects CD4+ T cells, macrophages,
and dendritic cells. It binds to CD4 receptor and co-receptors (CCR5 or
CXCR4) on the surface of these cells. - Fusion and Entry: After binding, the virus fuses with the host cell
membrane and releases its RNA and enzymes (reverse transcriptase,
integrase, and protease) into the cell. - Reverse Transcription: The viral RNA is reverse transcribed into DNA by
the enzyme reverse transcriptase. - Integration: The viral DNA integrates into the host cell’s DNA with the help
of the enzyme integrase, becoming a provirus. - Transcription and Translation: The provirus may lie dormant or become
active, producing viral RNA and proteins using the host cell’s machinery - Assembly and Budding: New viral particles are assembled from the viral
proteins and RNA within the host cell. They bud off from the host cell membrane,
often acquiring an envelope made of host cell membrane components. - Maturation and Release: The new viruses mature by protease-mediated
cleavage of viral polyproteins. Mature viruses are then released from the host cell
to infect other cells, often leading to destruction of the host cell in the process. - Immune Response: HIV evades the immune system by rapidly mutating its
surface proteins (e.g., gp120) and by infecting CD4+ T cells that play a crucial
role in coordinating the immune response. - Progression to AIDS: HIV progressively weakens the immune system by
selectively infecting and killing CD4+ T cells, leading to a decrease in immune
function. Without treatment, this can eventually result in acquired
immunodeficiency syndrome (AIDS), leaving the body susceptible to
opportunistic infections and cancers.
What causes HIV?
How can it be transmitted?
- HIV - a retrovirus that infects and replicates primarily in human CD4+ T cells and macrophages.
- HIV can be transmitted via:
- Direct contact: sexual intercourse via exchange of sexual fluid (most common)
- Blood-borne transmission: blood, blood products, or other fluids containing blood
(e.g., sharing contaminated needles & syringes) - Vertical transmission – before birth or during delivery breast milk
What are the risk factors of HIV?
- Have a current or former partner who is infected with HIV.
- Are from an area with high HIV prevalence.
- Are men who have sex with men (MSM).
- Are female sexual contacts of MSM.
- Are transwomen.
- Have had multiple sexual partners, engage in high-risk sexual practices such as
‘chemsex’, or have a history of other sexually transmitted infection (such as
syphilis, chlamydia, and gonorrhoea). - Have a history of injecting drug use.
- Are current or previous sex workers.
- Have been raped.
- Have had blood transfusions, transplants, or other risk-prone procedures in
countries without rigorous procedures for HIV screening. - Have had an occupational exposure such as a needle stick injury.
How many stages of HIV are there? (3)
Stage 1- Primary HIV Infection
* Flu-like symptoms
* Stage 2 – Longstanding HIV
* Majority are asymptomatic but some may still have symptoms
* Symptoms can vary from minimal to more severe
* Stage 3 – AIDS
* CD4 level ˂ 200 cells/mm3
Diagnosis of HIV
What do you ask in the full history?
Symptoms - fever, weight loss, sweats, diarrhoea, lymphadenopathy, skin rashes, cough, oral candida, and aphthous
ulcers
* Possible risk factors
* Past medical history - including hospital admissions
Diagnosis of HIV
What do you examine the patient for?
- Rash
- Signs of immunocompromise – e.g., oral candidiasis
- Opportunistic infection – TB, CMV
- Cancer
How can HIV be monitored?
- Monitoring of HIV is usually carried out in specialist clinics using the CD4 lymphocyte cell (CD4) count and viral load.
CD4 count
* The CD4 count reflects the degree of immunosuppression in people infected with HIV
* Healthy person - CD4 count > 500 cells/microlitre
* CD4 counts ˂ 200 cells/microlitre are most at risk of HIV-related opportunistic infections and cancers.
* If treatment is started at CD4 counts above 500 cells per microlitre, rather than later, prognosis is improved.
- Monitoring of HIV is usually carried out in specialist clinics using the CD4
lymphocyte cell (CD4) count and viral load. - Viral load
- Viral load reflects rates of viral replication and is measured using a polymerase chain
reaction (PCR) test. - A rising viral load non-adherence to ART? resistance to one or more antiretroviral
drugs? or an interaction with another medication? - Viral load ranges from undetectable (less than 20–50 copies of viral genome/mL
blood) to over a million copies/ml. - The degree of viral replication is linked to the rate of CD4 decline and
therefore disease progression
CD4 cell count or Viral load more important in diagnosis of HIV?
When patients are taking HIV treatment,
the viral load is a more important indicator
of their health and of the effectiveness of
the treatment than the CD4 cell count
Aims of treatment
- achieve an undetectable viral load
- preserve immune function
- reduce the mortality and morbidity associated with chronic HIV
infection - reduce onward transmission of HIV
- minimise drug toxicity
- Treatment with a combination of ART aims to improve the physical and psychological well-being of infected people
Initiation of treatment
- ALL patients diagnosed as being HIV positive should be offered immediate treatment, irrespective of CD4 cell counts.
- Important things to consider:
- Strict adherence to treatment over many years is required - Low
adherence can be associated with drug resistance, progression to AIDS, and death. - The treatment regimen should take into account dosing convenience, potential drug interactions, clinical symptoms, and comorbidities
Initiation of treatment:
What are the 4 main classes of anti-HIV drug
Standard treatment for people starting HIV treatment for the first time is a combination of three different drugs (Two drug combination is now possible)
- Nucleoside reverse transcriptase inhibitors (NRTIs)
- Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
- Boosted protease inhibitors
- Integrase inhibitors
Initiation of treatment
- In a three-drug combination, two of the medications are sometimes called the ‘backbone’ of the combination.
- Backbone are two drugs from the nucleoside/nucleotide reverse
transcriptase inhibitor (NRTI) class.
-BHIVA usually recommends a backbone of tenofovir and
emtricitabine. - The recommended first-line HIV treatments for most people all include an integrase inhibitor:
-either dolutegravir or bictegravir
Initiation of treatment
Examples of:
Emtricabine, Tenofovir alafenamide
Dolutegravir, Bictegravir
Adverse effects of antiretroviral therapy:
ART can have multiple adverse effects, some of which can be
serious or life threatening
* Consider whether specialist advice or hospital admission is required.
* Do not stop any ART or adjust the dose without specialist advice.
* Be aware that some minor adverse effects may herald a major
adverse effect, and have a low threshold for seeking specialist
advice.
* Serious adverse effects may present in unusual ways such as osteoporosis, Fanconi syndrome, or lactic acidosis
