HIV resistance testing US Medical PG Practice Questions and MCQs
Practice US Medical PG questions for HIV resistance testing. These multiple choice questions (MCQs) cover important concepts and help you prepare for your exams.
HIV resistance testing US Medical PG Question 1: A 32-year-old man comes to the physician for a follow-up examination 1 week after being admitted to the hospital for oral candidiasis and esophagitis. His CD4+ T lymphocyte count is 180 cells/μL. An HIV antibody test is positive. Genotypic resistance assay shows the virus to be susceptible to all antiretroviral therapy regimens and therapy with dolutegravir, tenofovir, and emtricitabine is initiated. Which of the following sets of laboratory findings would be most likely on follow-up evaluation 3 months later?
$$$ CD4 +/CD8 ratio %%% HIV RNA %%% HIV antibody test $$$
- A. ↓ ↓ negative
- B. ↑ ↑ negative
- C. ↓ ↑ negative
- D. ↑ ↓ positive (Correct Answer)
- E. ↓ ↑ positive
HIV resistance testing Explanation: ***↑ ↓ positive***
- With effective **antiretroviral therapy (ART)**, the **CD4+/CD8 ratio** would increase as **CD4+ T cell counts rise** and **CD8+ T cell counts decrease**.
- **HIV RNA (viral load)** would significantly decrease (ideally to undetectable levels) due to the suppression of viral replication, but HIV antibodies would remain positive indefinitely.
*↓ ↓ negative*
- A decrease in the **CD4+/CD8 ratio** and **HIV RNA** (viral load) along with a negative **HIV antibody test** is inconsistent with successful ART.
- A negative HIV antibody test would mean the patient was never infected, which contradicts the initial positive result and symptoms.
*↑ ↑ negative*
- An increase in the **CD4+/CD8 ratio** is expected with ART, but an increase in **HIV RNA** (viral load) indicates treatment failure.
- A negative **HIV antibody test** is impossible after a confirmed positive result, regardless of treatment success.
*↓ ↑ negative*
- A decrease in the **CD4+/CD8 ratio** would suggest worsening immune function, while an increase in **HIV RNA** indicates treatment failure.
- A negative **HIV antibody test** is not possible once a patient has developed antibodies to HIV.
*↓ ↑ positive*
- A decrease in the **CD4+/CD8 ratio** would indicate immune decline, contrary to the expected improvement with effective ART.
- An increase in **HIV RNA (viral load)** would signify treatment failure, even if HIV antibodies remain positive.
HIV resistance testing US Medical PG Question 2: An HIV-positive 48-year-old man comes to the emergency department because of a 3-month history of recurrent, painful mouth ulcers. This time, the pain is so severe that the patient cannot eat. He has a history of a seizure disorder but currently does not take any medications. He appears very ill. His temperature is 39.0°C (102.2°F). Physical examination shows numerous vesicular ulcerations on the lips and sloughing of the gums, buccal mucosa, and hard palate. Genetic analysis of the pathogen isolated from the lesions shows a mutation in a gene encoding viral phosphotransferases. Which of the following drugs is the most appropriate treatment?
- A. Acyclovir
- B. Famciclovir
- C. Cidofovir
- D. Ganciclovir
- E. Foscarnet (Correct Answer)
HIV resistance testing Explanation: ***Foscarnet***
- The presence of **recurrent, painful vesicular ulcerations** in an HIV-positive patient, especially with **gingivostomatitis-like symptoms** (sloughing gums, buccal mucosa), points to a severe **herpes simplex virus (HSV) infection**, likely resistant to nucleoside analogues given the **phosphotransferase mutation**.
- **Foscarnet** is a pyrophosphate analog that directly inhibits viral DNA polymerase without requiring phosphorylation by viral thymidine kinase, making it effective against **acyclovir-resistant HSV** strains, which often develop resistance via mutations in viral phosphotransferases or thymidine kinase.
*Acyclovir*
- **Acyclovir** is a nucleoside analog that requires phosphorylation by viral thymidine kinase (a phosphotransferase) to become active.
- A **mutation in viral phosphotransferases** would render the virus resistant to acyclovir, making it an ineffective treatment.
*Famciclovir*
- **Famciclovir** is a prodrug of penciclovir, which is also a nucleoside analog that requires phosphorylation by viral thymidine kinase for activation.
- Similar to acyclovir, a **mutation in viral phosphotransferases** would lead to resistance and make famciclovir ineffective.
*Cidofovir*
- **Cidofovir** is a nucleotide analog that does not require phosphorylation by viral enzymes for its initial activation.
- While it can be effective against some resistant strains, **foscarnet is generally preferred** for severe, resistant HSV infections as cidofovir is primarily used for **CMV retinitis** and is associated with significant nephrotoxicity.
*Ganciclovir*
- **Ganciclovir** is a nucleoside analog primarily used for **CMV infections**, and it also requires phosphorylation by viral kinases for activation.
- It is not the first-line treatment for HSV, and the **phosphotransferase mutation** would likely confer resistance to ganciclovir as well.
HIV resistance testing US Medical PG Question 3: A 17-year-old girl comes to the urgent care center after testing negative for HIV. She recently had sexual intercourse for the first time and had used a condom with her long-term boyfriend. She has no personal history of serious illness and no history of sexually transmitted infections. However, the patient is still worried about the possibility she has HIV despite the negative HIV test. She states that the package insert of the HIV test shows that of 100 patients who are found to be HIV-positive on PCR, 91 tested positive via the HIV test. Later in the day, a 23-year-old woman with a history of genitourinary chlamydia infection also comes to the urgent care center after testing negative for HIV. She states that she recently had unprotected intercourse with “someone who might have HIV.” If the test is conducted a second time on the 23-year-old patient, how will its performance compare to a second test conducted on the 17-year-old patient?
- A. Decreased positive predictive value
- B. Increased validity
- C. Increased sensitivity
- D. Decreased negative predictive value (Correct Answer)
- E. Increased specificity
HIV resistance testing Explanation: ***Decreased negative predictive value***
- The 23-year-old patient has a higher **pre-test probability** of HIV due to unprotected intercourse with a high-risk partner and a history of STIs, which increases the likelihood of HIV exposure and acquisition.
- A higher pre-test probability for a disease will **decrease the negative predictive value** of a test while increasing its positive predictive value, even if the test's sensitivity and specificity remain constant.
*Decreased positive predictive value*
- A higher **pre-test probability** (like in the 23-year-old patient) actually **increases the positive predictive value** of a diagnostic test, given the same sensitivity and specificity.
- The positive predictive value reflects the probability that a positive test result correctly identifies someone with the disease.
*Increased validity*
- **Validity** refers to how well a test measures what it is supposed to measure (accuracy), and it is not expected to change based on the individual patient's risk factors.
- The intrinsic properties of the test (sensitivity and specificity) determine its validity, not the prevalence of the disease or the patient's pre-test probability.
*Increased sensitivity*
- **Sensitivity** is a fixed characteristic of the test itself, defined as the proportion of true positives correctly identified by the test.
- A patient's individual risk factors or pre-test probability do not alter the inherent sensitivity of the HIV test.
*Increased specificity*
- **Specificity** is also a fixed characteristic of the test, representing the proportion of true negatives correctly identified.
- The test's specificity does not change based on the prevalence of HIV in the population or the patient's individual risk for the disease.
HIV resistance testing US Medical PG Question 4: A 27-year-old man interested in pre-exposure therapy for HIV (PrEP) is being evaluated to qualify for a PrEP study. In order to qualify, patients must be HIV- and hepatitis B- and C-negative. Any other sexually transmitted infections require treatment prior to initiation of PrEP. The medical history is positive for a prior syphilis infection and bipolar affective disorder, for which he takes lithium. On his next visit, the liver and renal enzymes are within normal ranges. HIV and hepatitis B and C tests are negative. Which of the following about the HIV test is true?
- A. It is a quantitative test used for screening purposes.
- B. It is a qualitative test used for screening purposes. (Correct Answer)
- C. A secondary reagent is needed to interpret the results.
- D. A known antigen binds directly to the patient's serum.
- E. An unknown antigen binds to the known serum.
HIV resistance testing Explanation: ***It is a qualitative test used for screening purposes.***
- **HIV screening tests** (e.g., 4th generation antibody/antigen combination assays) are typically **qualitative**, meaning they detect the presence or absence of HIV markers, not their exact amount.
- These tests are primarily used for broad **screening** of populations to identify potential cases of HIV infection.
*It is a quantitative test used for screening purposes.*
- **Quantitative tests** for HIV, such as viral load tests, measure the amount of virus in the blood and are typically used for monitoring disease progression or treatment effectiveness, not for initial screening.
- Screening tests are designed for high sensitivity to detect infection, even with low viral loads or early antibody responses, making a quantitative measurement less relevant for initial screening.
*A secondary reagent is needed to interpret the results.*
- While some complex immunoassays might involve multiple steps, modern **HIV screening tests** often use advanced technologies that directly yield results, making a separate secondary reagent for interpretation generally unnecessary.
- The results are typically indicated by a color change or a signal detected by an instrument, without requiring an additional interpretive reagent.
*A known antigen binds directly to the patient's serum.*
- **HIV antibody tests** detect **antibodies** produced by the patient's immune system in response to HIV infection.
- In such tests, **known HIV antigens** (from the test kit) bind to **HIV-specific antibodies present in the patient's serum**, not to serum components directly.
- This option is incorrect because it omits the critical role of antibodies as the target molecules being detected.
*An unknown antigen binds to the known serum.*
- This statement describes a different type of immunological assay where an unknown antigen is being identified using a known antibody, which is contrary to how **HIV screening tests** for infection are typically structured.
- **HIV screening tests** use known components (e.g., HIV antigens or antibodies) in the test kit to detect unknown components (e.g., HIV antibodies or viral antigens) in the patient's sample.
HIV resistance testing US Medical PG Question 5: A 26-year-old nurse presents 12 hours after she accidentally stuck herself with a blood-contaminated needle. She reported the accident appropriately and now seeks post-exposure prophylaxis. She does not have any complaints at the moment of presentation. Her vital signs include: blood pressure 125/80 mm Hg, heart rate 71/min, respiratory rate 15/min, and temperature 36.5℃ (97.7℉). Physical examination is unremarkable. The nurse has prescribed a post-exposure prophylaxis regimen which includes tenofovir, emtricitabine, and raltegravir. How will tenofovir change the maximum reaction rate (Vm) and Michaelis constant (Km) of the viral reverse transcriptase?
- A. Vm will decrease, Km will increase
- B. Vm and Km will both decrease
- C. Vm will stay the same, Km will increase
- D. Vm and Km will both increase
- E. Vm will decrease, Km will stay the same (Correct Answer)
HIV resistance testing Explanation: ***Vm will decrease, Km will stay the same***
- **Tenofovir** is a **nucleotide reverse transcriptase inhibitor (NtRTI)** that acts as a **competitive substrate analog**. Once phosphorylated to **tenofovir diphosphate**, it competes with natural deoxyadenosine triphosphate (dATP) for incorporation into the viral DNA chain.
- Upon incorporation, tenofovir acts as a **chain terminator** because it lacks a 3'-hydroxyl group necessary for further DNA elongation. This **irreversibly inactivates** the enzyme-DNA complex, effectively reducing the **maximum reaction rate (Vm)** by decreasing the amount of functional enzyme available.
- Since tenofovir competes with natural nucleotides but doesn't affect the enzyme's affinity for its natural substrates, the **Michaelis constant (Km) remains unchanged**. The inhibition pattern shows characteristics of competitive inhibition with irreversible chain termination.
*Vm will decrease, Km will increase*
- This pattern is characteristic of a **mixed inhibitor**, where the inhibitor can bind to both the free enzyme and the enzyme-substrate complex, reducing Vm while also decreasing substrate affinity (increasing Km).
- While tenofovir does reduce Vm through chain termination, it does not significantly alter the enzyme's affinity for natural nucleotide substrates. Tenofovir diphosphate **competes directly** with dATP rather than binding to an allosteric site, so Km remains unchanged rather than increasing.
*Vm and Km will both decrease*
- This effect is typical of an **uncompetitive inhibitor**, which binds only to the **enzyme-substrate complex**. Uncompetitive inhibitors decrease both Vm and Km, implying increased apparent substrate affinity.
- Tenofovir does not function as an uncompetitive inhibitor. As a **nucleotide analog**, it competes for the active site and gets incorporated into DNA, causing chain termination. This mechanism does not involve preferential binding to the enzyme-substrate complex that would decrease Km.
*Vm will stay the same, Km will increase*
- This describes **pure reversible competitive inhibition**, where the inhibitor competes with substrate for the active site but can be overcome by increasing substrate concentration, leaving Vm unchanged.
- While tenofovir diphosphate does **compete with natural nucleotides**, it acts as a **suicide substrate** that causes irreversible chain termination once incorporated. This **permanently inactivates** the enzyme-DNA complex, reducing the pool of functional enzyme and thus decreasing Vm, distinguishing it from simple reversible competitive inhibition.
*Vm and Km will both increase*
- An increase in both Vm and Km is not a standard pattern for enzyme inhibition and would suggest **reduced substrate affinity** with paradoxically increased catalytic capacity, which is inconsistent with any inhibitory mechanism.
- This scenario contradicts the **intended therapeutic effect** of tenofovir, which is to inhibit HIV reverse transcriptase activity and prevent viral replication, not to enhance enzyme function.
HIV resistance testing US Medical PG Question 6: A 23-year-old male with a homozygous CCR5 mutation is found to be immune to HIV infection. The patient’s CCR5 mutation interferes with the function of which viral protein?
- A. gp41
- B. Reverse transcriptase
- C. pp17
- D. gp120 (Correct Answer)
- E. p24
HIV resistance testing Explanation: ***gp120***
- The **gp120 protein** on the HIV envelope is responsible for binding to the **CD4 receptor** and the **coreceptor CCR5** or CXCR4 on host cells, which is the initial step for viral entry.
- A homozygous **CCR5 mutation** (specifically the **CCR5-Δ32** deletion) prevents HIV from using this coreceptor, thereby blocking the binding of gp120 and subsequent viral entry.
*gp41*
- **gp41** is another envelope protein that, after gp120 binds to CD4 and a coreceptor, undergoes a conformational change to mediate **fusion** of the viral and host cell membranes.
- While essential for entry, gp41 acts downstream of gp120's primary binding to the coreceptor, so a CCR5 mutation primarily affects gp120's ability to engage with the cell.
*Reverse transcriptase*
- **Reverse transcriptase** is a viral enzyme responsible for **converting viral RNA into DNA** once the virus has already entered the host cell cytoplasm.
- A CCR5 mutation prevents viral entry, thus the activity of reverse transcriptase is not directly interfered with by the mutation itself but rather by the lack of cellular access.
*pp17*
- **pp17**, also known as **matrix protein**, is an internal structural protein that plays a role in the assembly of new virions and guiding the **reverse transcribed DNA** into the nucleus.
- This protein is involved in later stages of the viral life cycle *after* entry and integration, and its function is not directly blocked by a CCR5 mutation.
*p24*
- **p24** is the major **capsid protein** that forms the core of the HIV virus, enclosing the viral RNA and enzymes.
- It is critical for maintaining the structural integrity of the virus and is a key target for diagnostic tests, but it does not directly participate in the initial binding and entry process that is affected by a CCR5 mutation.
HIV resistance testing US Medical PG Question 7: An investigator is studying the mechanism of HIV infection in cells obtained from a human donor. The effect of a drug that impairs viral fusion and entry is being evaluated. This drug acts on a protein that is cleaved off of a larger glycosylated protein in the endoplasmic reticulum of the host cell. The protein that is affected by the drug is most likely encoded by which of the following genes?
- A. gag
- B. env (Correct Answer)
- C. tat
- D. pol
- E. rev
HIV resistance testing Explanation: ***env***
- The **env (envelope) gene** of HIV encodes for the precursor protein **gp160**, which is then cleaved by host cellular proteases into **gp120** and **gp41** within the endoplasmic reticulum.
- **gp120** and **gp41** together form the viral envelope glycoproteins responsible for viral binding to host cells and **fusion/entry**, making them the target of drugs that impair these processes.
*gag*
- The **gag (group-specific antigen) gene** encodes for structural proteins of the viral core, such as **p24 (capsid protein)**, p17 (matrix protein), and p7 (nucleocapsid protein).
- These proteins are primarily involved in the assembly of new virions and do not directly mediate viral fusion and entry.
*tat*
- The **tat (trans-activator of transcription) gene** encodes a regulatory protein that significantly enhances the transcription of viral genes.
- It plays a crucial role in the viral life cycle by increasing the efficiency of HIV gene expression, but it is not directly involved in viral fusion or entry.
*pol*
- The **pol (polymerase) gene** encodes for essential viral enzymes, including **reverse transcriptase**, integrase, and protease.
- These enzymes are critical for converting viral RNA into DNA, integrating viral DNA into the host genome, and cleaving viral polyproteins, respectively, but they are not involved in mediating viral entry.
*rev*
- The **rev (regulator of virion expression) gene** encodes a regulatory protein that facilitates the transport of unspliced and partially spliced viral RNAs from the nucleus to the cytoplasm.
- This transport is crucial for the synthesis of structural and enzymatic proteins and for packaging viral RNA into new virions, but it does not directly participate in viral fusion and entry.
HIV resistance testing US Medical PG Question 8: A 29-year-old woman tests positive for HIV during pregnancy screening. She is concerned about transmission to her baby. Which of the following interventions most significantly reduces the risk of vertical transmission?
- A. Avoiding breastfeeding only
- B. Cesarean delivery only
- C. Antiretroviral therapy during pregnancy and labor (Correct Answer)
- D. Maternal immunization
HIV resistance testing Explanation: ***Antiretroviral therapy during pregnancy and labor***
- **Antiretroviral therapy (ART)** significantly reduces the **viral load** in the mother, thereby minimizing the risk of HIV transmission to the fetus during pregnancy and childbirth.
- When combined with other strategies like **cesarean section** and **avoidance of breastfeeding** in developed countries, ART can reduce vertical transmission rates to less than 1%.
*Avoiding breastfeeding only*
- While **avoiding breastfeeding** is a crucial intervention, especially in settings where safe alternatives are available, it addresses only one mode of transmission (postnatal).
- It does not prevent **in-utero** or **intrapartum transmission**, which are primary routes of vertical transmission if the viral load is high.
*Cesarean delivery only*
- **Cesarean delivery** can reduce the risk of transmission by avoiding exposure to maternal blood and secretions during vaginal delivery.
- However, it is most effective when the maternal **viral load is high** and is often combined with ART for maximum efficacy; it's less effective without ART.
*Maternal immunization*
- **Maternal immunization** involves administering vaccines to the mother to protect against specific infections, primarily bacterial or viral diseases like influenza or tetanus.
- It has **no direct impact** on the risk of HIV transmission, as there is currently no vaccine available for HIV.
HIV resistance testing US Medical PG Question 9: A 41-year-old HIV-positive male presents to the ER with a 4-day history of headaches and nuchal rigidity. A lumbar puncture shows an increase in CSF protein and a decrease in CSF glucose. When stained with India ink, light microscopy of the patient’s CSF reveals encapsulated yeast with narrow-based buds. Assuming a single pathogenic organism is responsible for this patient’s symptoms, which of the following diagnostic test results would also be expected in this patient?
- A. Ring-enhancing lesions on CT imaging
- B. Latex agglutination of CSF (Correct Answer)
- C. Cotton-wool spots on funduscopic exam
- D. Acid-fast oocysts in stool
- E. Frontotemporal atrophy on MRI
HIV resistance testing Explanation: **Latex agglutination of CSF**
- The presence of **encapsulated yeast with narrow-based buds** in the cerebrospinal fluid (CSF) on **India ink stain** is pathognomonic for **Cryptococcus neoformans**, the causative agent of **cryptococcal meningitis**.
- **Latex agglutination** is a rapid and highly sensitive test that detects the **cryptococcal capsular polysaccharide antigen** in CSF, making it an expected diagnostic finding.
*Ring-enhancing lesions on CT imaging*
- **Ring-enhancing lesions** are typically associated with **Toxoplasma gondii encephalitis** (toxoplasmosis) in HIV-positive patients, which would also present with focal neurological deficits.
- While cryptococcal meningitis can sometimes cause cryptococcomas that may enhance, these are less common and not the primary diagnostic feature.
*Cotton-wool spots on funduscopic exam*
- **Cotton-wool spots** are associated with **HIV retinopathy** or sometimes **cytomegalovirus (CMV) retinitis**, presenting as fluffy white lesions on the retina.
- These findings are indicative of microinfarctions in the retinal nerve fiber layer due to various causes, but not directly linked to fungal meningitis.
*Acid-fast oocysts in stool*
- **Acid-fast oocysts in stool** are characteristic of infections such as **cryptosporidiosis** or **isosporiasis**, which cause chronic diarrhea in immunocompromised individuals.
- These are gastrointestinal pathogens and would not directly lead to the neurological symptoms and CSF findings described in the patient.
*Frontotemporal atrophy on MRI*
- **Frontotemporal atrophy** is a feature of **neurocognitive disorders** such as **frontotemporal dementia** or **HIV-associated dementia (HAD)**, a chronic neurocognitive decline.
- While HAD can occur in HIV-positive individuals, it does not explain the acute presentation of headaches, nuchal rigidity, and specific CSF findings suggestive of an acute infectious process like meningitis.
HIV resistance testing US Medical PG Question 10: Four scientists were trying to measure the effect of a new inhibitor X on the expression levels of transcription factor, HNF4alpha. They measured the inhibition levels by using RT-qPCR. In short they converted the total mRNA of the cells to cDNA (RT part), and used PCR to amplify the cDNA quantifying the amplification with a dsDNA binding dye (qPCR part). Which of the following group characteristics contains a virus(es) that has the enzyme necessary to convert the mRNA to cDNA used in the above scenario?
- A. Enveloped, dimeric (+) ssRNA (Correct Answer)
- B. Enveloped, circular (-) ssRNA
- C. Nonenveloped, (+) ssRNA
- D. Nonenveloped, ssDNA
- E. Nonenveloped, circular dsDNA
HIV resistance testing Explanation: ***Enveloped, dimeric (+) ssRNA***
- This group describes **retroviruses**, which possess the enzyme **reverse transcriptase**.
- **Reverse transcriptase** is essential for converting their **RNA genome** into **cDNA**, a process analogous to the RT step in RT-qPCR.
- Examples include **HIV**, which is tagged to this topic.
*Enveloped, circular (-) ssRNA*
- This description does not accurately represent a major viral family.
- Most enveloped negative-sense RNA viruses have **linear or segmented genomes** (e.g., **Orthomyxoviruses**, **Bunyaviruses**), not circular.
- These viruses replicate using an **RNA-dependent RNA polymerase** to synthesize mRNA from their negative-sense RNA genome.
- They do not inherently carry or require **reverse transcriptase** for their life cycle.
*Nonenveloped, (+) ssRNA*
- These viruses, like **Picornaviruses**, directly use their positive-sense RNA as mRNA and replicate via an **RNA-dependent RNA polymerase**.
- They do not possess **reverse transcriptase** for cDNA synthesis.
*Nonenveloped, ssDNA*
- Viruses with a **single-stranded DNA genome**, such as **Parvoviruses**, replicate by first synthesizing a double-stranded DNA intermediate.
- Their replication machinery does not involve **reverse transcriptase** to convert RNA to DNA.
*Nonenveloped, circular dsDNA*
- Viruses in this group, like **Papillomaviruses** and **Polyomaviruses**, have a circular double-stranded DNA genome and replicate within the host nucleus using the host's DNA polymerase.
- They do not utilize or encode **reverse transcriptase** for their replication cycle.
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