VIROLOGY
1. Describe the structure and basic properties of HIV as a retrovirus.
2. Identify the viral causative agent for Kaposi Sarcoma
1. Answer:
HIV is a retrovirus. It contains two copies of single-stranded RNA as its genetic material and uses the enzyme reverse transcriptase to convert its RNA into DNA. The main structural genes are gag, pol and env. HIV has an envelope containing glycoproteins that help the virus attach to and enter host cells.
2. Human Herpes virus type 8
1. Describe the role of CD4+ T lymphocytes in HIV infection and explain the clinical significance of the CD4 count.
1. Answer:
CD4+ T lymphocytes are important cells of the immune system that coordinate immune responses. HIV infects and destroys CD4+ T cells. As the CD4 count decreases, the immune system becomes weaker and the patient becomes increasingly susceptible to opportunistic infections. A very low CD4 count, especially below 200 cells/µL, is associated with AIDS and a high risk of opportunistic infections.
1. List the 5 classes of ART and their examples: the group to list all the drugs gets the points
Answer:
1. Mention 3 complications of untreated VDS (vaginal discharge syndrome)
Ans (any of these) :
Pelvic inflammatory disease(PID)
Fallopian tube damage
Ectopic pregnancy
Preterm labour
Neonatal conjunctivitis and Resp infection
. What are the 3 periods in which vertical HIV transmission can occur :
Ans:
In utero (pregnancy)
Intrapartum - During birth
Postnatally - through breastfeeding
1. List 3 ways that HIV is tested and the order in which each tested component occurs ?
1. Answer:
Order of appearance after infection:
HIV RNA → p24 antigen → HIV antibodies
Define an opportunistic infection and explain how HIV infection predisposes patients to opportunistic infections.
Answer:
An opportunistic infection is an infection that occurs more easily or causes more severe disease when the immune system is weakened. HIV destroys CD4+ T cells, causing progressive immune suppression. This reduces the body's ability to control organisms that would normally be controlled by an intact immune system.
Explain the role of Ritonavir and its interaction with Cytochrome P450?
=Ritonavir is a potent inhibitor of CYP3A4, which is one of the enzymes in the Cytochrome P450 (CYP450) family.
Normally:
Drug → CYP3A4 → metabolism → lower drug concentration
But when ritonavir is present:
Ritonavir → inhibits CYP3A4 → less metabolism of the other drug → higher drug concentration + longer duration
2. Why do genital ulcers increase the risk of HIV transmission?
Ans : Genital ulcers disrupt normal mucosal barrier and cause inflammation. Therefore, recruiting CD4+ cells which are targeting by HIV making transmission/infection easier.
2. Name the three main modes of HIV transmission.
**Answer:**Sexual transmission, blood-borne transmission, and vertical transmission from mother to child.
4. Explain the concept of the HIV window period and its relevance to HIV testing.
Answer:
The HIV window period is the time between HIV infection and the point when a test can reliably detect the infection. During this period, a person may be infected and able to transmit HIV, but the test may still be negative because the viral markers have not reached detectable levels.
Question 1: Why is prophylaxis given to patients with advanced HIV when starting ART?
1. ART does not restore the immune system immediately. In patients with advanced HIV, the CD4 count may still be very low when ART is started, which means they remain highly susceptible to opportunistic infections. Giving them prophylaxis prevents them from getting specific opportunistic infections while the immune system is severely compromised
Answe (not so sure which was the correct answer)r:
ART suppresses HIV replication, but immune recovery takes time. Therefore, patients with advanced HIV can remain immunocompromised after starting ART. Chemoprophylaxis is given to prevent specific opportunistic infections while the CD4 count is still very low.
You are an Intern at GSH, and the attending doctor asked you to prescribe and explain adherence to ART and the pt is currectly on Tb treatment, you prescribed the 3 combination regimen which contains Retinovir, and the pt askes you, the use/significance of giving her Retinovir, using your knowledge of phamarcology in case 8 and 6 explain the mechanism of action of retinovir, and risk associated with not giving it
Answer:
Ritonavir is a protease inhibitor and is mainly used at low doses as a pharmacokinetic booster. It inhibits CYP3A4 in the liver and intestine, which decreases the metabolism of other protease inhibitors. This increases their concentration and prolongs their duration of action.
If ritonavir is not given when it is required for boosting, the concentration of the boosted protease inhibitor may fall, which can reduce its effectiveness and increase the risk of virological failure and development of drug resistance.
Explain the significance of syndromic approach to the management of STIs
3. 2.a) This is the syndromic approach which is empiric treatment, based on the clinical syndrome the patient presents with rather than waiting for lab confirmation of the specific causative organism.
b) Advantages
Answer:
This is the syndromic approach which is empiric treatment, based on the clinical syndrome the patient presents with rather than waiting for lab confirmation of the specific causative organism.
3. Give two factors that increase the risk of sexual transmission of HIV.
Answer: High viral load and inflammation/damage of the genital mucosa, for example from other STIs.
5. Explain the pathogenesis of HIV infection, including acute infection, seroconversion and progressive immune dysfunction.
Answer:
After HIV enters the body, it infects mainly CD4+ T cells and begins replicating. During acute infection, there is a high viral load and a rapid fall in CD4+ T cells. The immune system then produces antibodies against HIV, which is called seroconversion. Although the immune response reduces the viral load, HIV remains in the body. Continued viral replication and destruction of CD4+ T cells eventually causes progressive immune dysfunction and can lead to AIDS.
4. Explain how chronic inflammation is related to GALT translocation ?
Answer:
During your internal medicine rotation in year 4, you encounter a farmer who has stopped taking his ART because he doesn’t want to look weak, Using your pharmacology knowledge of resistance to ART and natural course of HIV infection from Virology and Immunodeficienceis from anatomical pathology, explain to him the risk associated and outcomes
Answer:
Stopping ART allows HIV replication to increase again. Because HIV has a high mutation rate, continued replication allows drug-resistant mutations to develop. The viral load can increase and the CD4 count can fall, causing progressive immune dysfunction. This increases the risk of opportunistic infections, HIV-associated malignancies, transmission of HIV and progression to AIDS. Poor adherence can therefore lead to virological failure and loss of future treatment options.
4. Describe the major clinical syndromes of sexually transmitted infections.
Answer:
The major clinical syndromes include:
Each syndrome can have several possible causative organisms, which is why syndromic management treats the likely causes based on the patient's clinical presentation.
. LO 17: Using the epidemiological concept of distribution, describe the HIV epidemic in South Africa with reference to:
Answer:
A child is born to an HIV-positive mother and needs to be tested for HIV. Which HIV test would you use, and why
Answer:
I would use an HIV nucleic acid test (NAT/PCR) to detect HIV RNA or DNA.
This is because the child may have maternal HIV antibodies that crossed the placenta. Therefore, antibody-based serological tests cannot reliably distinguish between antibodies produced by the child and maternal antibodies. NAT/PCR detects the virus itself, making it more appropriate for diagnosing HIV infection in infants.
5. Explain why CD4+ T cells in the gastrointestinal tract (GIT) are destroyed so early in HIV infection. How does this loss disrupt the mucosal barrier, and what immunologic consequences follow microbial translocation across the gut?
ANSWER
Early GIT Depletion: The gastrointestinal tract mucosa contains the majority of the body's lymphoid tissue (GALT), where CCR5-expressing memory CD4+ T cells are densely concentrated. HIV selectively targets and rapidly destroys these CD4+ cells with the CCR5 mucosal T cells within the first few weeks of primary infection.
Disruption & Translocation:
Depletion of mucosal T-helper cells disrupts the epithelial tight junctions and mucosal immunity.
The mucosal barrier becomes compromised leading to a leaky gut, allowing bacterial products (e.g., Lipopolysaccharide/LPS) from the intestinal lumen to translocate into the systemic circulation.
Systemic microbial translocation acts as a continuous trigger for widespread innate and adaptive immune activation, driving systemic chronic inflammation and accelerated immune exhaustion.
5. Explain the rationale for combination antiretroviral therapy and how it prevents the development of drug resistance.
Answer:
HIV has a high mutation rate due to RT making mistakes during replication so using multiple drugs reduces the likelihood of the virus developing resistance to all of the drugs at the same time.
5. Classify sexually transmitted infections according to common clinical syndromes (i.e. Genital ulcer disease, urethritis, cervicitis, and vaginitis) and describe their clinical features.
Answer:
STIs can be classified according to the main clinical syndrome they produce:
Genital ulcer disease: genital ulcers, which may be painful or painless, with or without lymphadenopathy.
Urethritis: urethral inflammation causing urethral discharge and dysuria.
Cervicitis: inflammation of the cervix which may cause abnormal vaginal discharge, cervical discharge or bleeding.
Vaginitis: vaginal inflammation causing vaginal discharge, itching, irritation or abnormal vaginal odour.
LO1:HIV exhibits a high mutation rate and extensive genetic diversity. Using your knowledge of HIV replication, explain TWO mechanisms responsible for this diversity and discuss why it presents a challenge for vaccine development
Genetic diversity and vaccine challenges