HIV structure and replication cycle — MCQs

10 questions

A 49-year-old homeless man comes to the emergency department because of fatigue, cough, and worsening shortness of breath for 2 weeks. He was diagnosed with HIV-infection 25 years ago but has never had any symptoms. He has always refused to take antiretroviral medication. Pulmonary examination shows diffuse crackles over bilateral lower lung fields. An x-ray of the chest shows diffuse, symmetrical interstitial infiltrates. His serum level of beta-d-glucan is elevated. Further testing shows a heterozygous mutation that prevents entry of HIV into macrophages. Which of the following proteins is most likely affected by the mutation in this patient?

A 25-year-old sexually active male presents to an internal medicine physician for a routine health check up after having several unprotected sexual encounters. After appropriate testing the physician discusses with the patient that he is HIV+ and must be started on anti-retroviral treatment. Which of the following medications prescribed acts on the gp41 subunit of the HIV envelope glycoprotein?

An investigator is studying the rate of multiplication of hepatitis C virus in hepatocytes. The viral genomic material is isolated, enzymatically cleaved into smaller fragments and then separated on a formaldehyde agarose gel membrane. Targeted probes are then applied to the gel and visualized under x-ray. Which of the following is the most likely structure being identified by this test?

A 24-year-old male presents to the emergency room with a cough and shortness of breath for the past 3 weeks. You diagnose Pneumocystis jiroveci pneumonia (PCP). An assay of the patient's serum reveals the presence of viral protein p24. Which of the following viral genes codes for this protein?

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?

An investigator is studying the replication of a virus in denucleated embryonic fibroblasts. After the fibroblasts are infected with the virus, viral proteins are directly translated from the virion's genetic material using fibroblast ribosomes. The resultant large polypeptides are then cleaved into smaller peptides by viral proteases to generate mature viral proteins. Finally, the virion's genetic material is replicated using a protein translated from the virion's genetic material. Which of the following is the most likely virus being evaluated in this study?

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 44-year-old with a past medical history significant for human immunodeficiency virus infection presents to the emergency department after he was found to be experiencing worsening confusion. The patient was noted to be disoriented by residents and staff at the homeless shelter where he resides. On presentation he reports headache and muscle aches but is unable to provide more information. His temperature is 102.2°F (39°C), blood pressure is 112/71 mmHg, pulse is 115/min, and respirations are 24/min. Knee extension with hips flexed produces significant resistance and pain. A lumbar puncture is performed with the following results: Opening pressure: Normal Fluid color: Clear Cell count: Increased lymphocytes Protein: Slightly elevated Which of the following is the most likely cause of this patient's symptoms?

A 32-year-old HIV positive male presents to the office complaining of difficulty swallowing and bad breath for the past couple of months. Upon further questioning, he says, "it feels like there’s something in my throat". He says that the difficulty is sometimes severe enough that he has to skip meals. He added that it mainly occurs with solid foods. He is concerned about his bad breath since he has regular meetings with his clients. Although he is on antiretroviral medications, he admits that he is noncompliant. On examination, the patient is cachectic with pale conjunctiva. On lab evaluation, the patient’s CD4+ count is 70/mm3. What is the most likely cause of his symptoms?

Q10

A 45-year-old man comes to the physician because of a 3-week history of progressive diarrhea and a 2.2-kg (5-lb) weight loss. During the past week, he has had six small bloody stools daily. He is employed as a sales manager and regularly flies to South America. He has HIV, gastroesophageal reflux disease, and hypertension. Current medications include chlorthalidone, omeprazole, emtricitabine, tenofovir, and efavirenz. He reports taking efavirenz irregularly. He is 175 cm (5 ft 9 in) tall and weighs 64 kg (143 lb); BMI is 22 kg/m2. His temperature is 38.1°C (100.6°F), pulse is 91/min, and blood pressure is 116/69 mm Hg. The abdomen is scaphoid. Bowel sounds are normal. His CD4+ T-lymphocyte count is 44/mm3 (N ≥ 500), leukocyte count is 6,000/mm3, and erythrocyte sedimentation rate is 12 mm/h. Colonoscopy shows areas of inflammation scattered throughout the colon with friability, granularity, and shallow linear ulcerations. The intervening mucosa between areas of inflammation appears normal. A biopsy specimen is shown. Which of the following is the most likely cause of this patient's symptoms?

HIV structure and replication cycle US Medical PG Practice Questions and MCQs

Question 1: A 49-year-old homeless man comes to the emergency department because of fatigue, cough, and worsening shortness of breath for 2 weeks. He was diagnosed with HIV-infection 25 years ago but has never had any symptoms. He has always refused to take antiretroviral medication. Pulmonary examination shows diffuse crackles over bilateral lower lung fields. An x-ray of the chest shows diffuse, symmetrical interstitial infiltrates. His serum level of beta-d-glucan is elevated. Further testing shows a heterozygous mutation that prevents entry of HIV into macrophages. Which of the following proteins is most likely affected by the mutation in this patient?

A. ICAM-1
B. Gp120
C. CD4
D. P antigen
E. CCR5 (Correct Answer)

Explanation: ***CCR5*** - The mutation preventing HIV entry into **macrophages** points to an issue with a coreceptor, most commonly **CCR5**, which is crucial for macrophage-tropic HIV strains. - A **heterozygous mutation** in CCR5 (CCR5-Δ32) can confer partial resistance to HIV-1 infection, explaining why the patient has been asymptomatic for 25 years despite refusing antiretroviral therapy. - This is a well-documented host genetic factor that slows HIV disease progression. *ICAM-1* - **ICAM-1 (Intercellular Adhesion Molecule 1)** is involved in cell adhesion and immune cell trafficking, but not directly in HIV entry into macrophages. - Mutations in ICAM-1 would not specifically prevent HIV entry, nor would it explain the long-term asymptomatic status in an HIV-positive individual. *Gp120* - **Gp120** is an HIV envelope glycoprotein that binds to the **CD4 receptor** and a coreceptor (CCR5 or CXCR4) on host cells. - While gp120 is essential for HIV entry, it is a **viral protein**; the question asks about a mutation in a **host protein** that prevents viral entry. *CD4* - **CD4** is the primary receptor for HIV on T cells and macrophages, essential for viral entry. - However, a **heterozygous CD4 mutation** would not provide meaningful protection against HIV, as one functional copy would be sufficient for viral entry. - In contrast, heterozygous **CCR5-Δ32** mutation provides documented partial resistance, making CCR5 the better answer given this patient's 25-year asymptomatic course. *P antigen* - **P antigen** typically refers to a red blood cell antigen and is not involved in HIV entry into macrophages. - There is no known direct association between P antigen and HIV susceptibility or disease progression.

Question 2: A 25-year-old sexually active male presents to an internal medicine physician for a routine health check up after having several unprotected sexual encounters. After appropriate testing the physician discusses with the patient that he is HIV+ and must be started on anti-retroviral treatment. Which of the following medications prescribed acts on the gp41 subunit of the HIV envelope glycoprotein?

A. Zidovudine
B. Saquinavir
C. Enfuvirtide (Correct Answer)
D. Amantadine
E. Rimantadine

Explanation: ***Enfuvirtide*** - **Enfuvirtide** is a **fusion inhibitor** that binds specifically to the **gp41 subunit** of the HIV envelope glycoprotein. - By binding to gp41, Enfuvirtide prevents the **fusion of the viral and host cell membranes**, thereby blocking viral entry and replication. *Zidovudine* - **Zidovudine** is a **nucleoside reverse transcriptase inhibitor (NRTI)**. - It works by inhibiting the enzyme **reverse transcriptase**, which is responsible for converting viral RNA into DNA. *Saquinavir* - **Saquinavir** is a **protease inhibitor (PI)**. - This drug works by inhibiting the **HIV protease enzyme**, which is crucial for cleaving viral polyproteins into functional proteins required for viral assembly and maturation. *Amantadine* - **Amantadine** is an **antiviral agent** primarily used to treat **influenza A**. - It works by interfering with the **M2 proton channel** of the influenza A virus, thus inhibiting viral uncoating. *Rimantadine* - **Rimantadine** is another **antiviral agent** used for **influenza A treatment and prophylaxis**. - Similar to amantadine, it targets the **M2 proton channel** of the influenza A virus, preventing the uncoating step necessary for viral replication.

Question 3: An investigator is studying the rate of multiplication of hepatitis C virus in hepatocytes. The viral genomic material is isolated, enzymatically cleaved into smaller fragments and then separated on a formaldehyde agarose gel membrane. Targeted probes are then applied to the gel and visualized under x-ray. Which of the following is the most likely structure being identified by this test?

A. Lipid-linked oligosaccharides
B. Transcription factors
C. Polypeptides
D. Ribonucleic acids (Correct Answer)
E. Deoxyribonucleic acids

Explanation: ***Ribonucleic acids*** - The description of isolating "viral genomic material," which is then "enzymatically cleaved" and run on a "formaldehyde agarose gel," followed by the application of "targeted probes" and X-ray visualization, perfectly matches the technique of **Northern blotting**. - Northern blotting is used to detect and quantify specific **RNA sequences**, which is consistent with the hepatitis C virus being an RNA virus. *Lipid-linked oligosaccharides* - These molecules are involved in protein glycosylation and are typically analyzed using techniques like **mass spectrometry** or **chromatography**, not Northern blotting. - They are not nucleic acid material, which is implied by "viral genomic material" and enzymatic cleavage steps. *Transcription factors* - **Transcription factors** are proteins that regulate gene expression and would typically be identified using techniques like **Western blotting** (for protein detection) or Electrophoretic Mobility Shift Assay (EMSA) for DNA binding. - They are not directly "genomic material" that would be cleaved and run on an agarose gel in this manner. *Polypeptides* - **Polypeptides** are chains of amino acids, i.e., proteins, which are normally detected using **Western blotting** after separation on an SDS-PAGE gel. - The use of "formaldehyde agarose gel" and "enzymatic cleavage" points specifically to nucleic acid analysis, not protein analysis. *Deoxyribonucleic acids* - While DNA is genomic material and is often analyzed similarly, the use of a **formaldehyde agarose gel** is characteristic of RNA electrophoresis because formaldehyde prevents RNA from forming secondary structures. - Furthermore, hepatitis C is a **single-stranded RNA virus**, meaning its genome is RNA, not DNA.

Question 4: A 24-year-old male presents to the emergency room with a cough and shortness of breath for the past 3 weeks. You diagnose Pneumocystis jiroveci pneumonia (PCP). An assay of the patient's serum reveals the presence of viral protein p24. Which of the following viral genes codes for this protein?

A. gag (Correct Answer)
B. pol
C. rev
D. env
E. tat

Explanation: ***gag*** - The **gag gene** (group-specific antigen) in HIV codes for structural proteins of the virus, including **p24**, which forms the viral capsid. - The presence of **p24 protein** in the serum is a key marker for **HIV infection**, particularly in the early stages, as it indicates active viral replication. *pol* - The **pol gene** codes for essential viral enzymes such as **reverse transcriptase**, **integrase**, and **protease**, which are crucial for the HIV life cycle. - While vital for viral replication, the **pol gene products** are enzymes involved in processing and replication, not the structural capsid protein p24. *rev* - The **rev gene** (regulator of expression of virion proteins) codes for the **Rev protein**, which regulates the export of HIV mRNAs from the nucleus to the cytoplasm. - This regulatory protein ensures the efficient synthesis of structural and enzymatic proteins but does not directly code for the p24 capsid protein. *env* - The **env gene** (envelope) codes for the viral envelope glycoproteins **gp160**, which is cleaved into **gp120** and **gp41**. - These proteins are critical for viral entry into host cells by binding to CD4 receptors and co-receptors, but they are distinct from the p24 capsid protein. *tat* - The **tat gene** (trans-activator of transcription) codes for the **Tat protein**, a powerful trans-activator that enhances the transcription of HIV RNA. - Tat plays a crucial role in increasing the efficiency of viral gene expression but does not code for structural components like the p24 capsid.

Question 5: 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

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.

Question 6: An investigator is studying the replication of a virus in denucleated embryonic fibroblasts. After the fibroblasts are infected with the virus, viral proteins are directly translated from the virion's genetic material using fibroblast ribosomes. The resultant large polypeptides are then cleaved into smaller peptides by viral proteases to generate mature viral proteins. Finally, the virion's genetic material is replicated using a protein translated from the virion's genetic material. Which of the following is the most likely virus being evaluated in this study?

A. Parvovirus
B. Human immunodeficiency virus
C. Measles virus
D. Molluscum contagiosum virus
E. Coxsackievirus (Correct Answer)

Explanation: ***Coxsackievirus*** - The description of **direct translation** from viral genetic material, **polyprotein cleavage by viral proteases**, and replication by a virally encoded protein is characteristic of **positive-sense single-stranded RNA viruses** like Coxsackievirus. - This process mirrors the replication strategy of **picornaviruses**, which include Coxsackievirus, where the genomic RNA acts directly as mRNA. - Critically, picornaviruses replicate entirely in the **cytoplasm**, allowing them to function in **denucleated cells** as described in the study. *Parvovirus* - Parvoviruses are **single-stranded DNA viruses** and require the host cell to be in **S-phase** to replicate their DNA, using host enzymes in the **nucleus**. - They **cannot replicate in denucleated cells** as they depend on nuclear host cell machinery. - They do not typically use **polyprotein cleavage** as their primary mechanism for generating mature viral proteins. *Human immunodeficiency virus* - HIV is a **retrovirus** (RNA virus) that requires **reverse transcriptase** to convert its RNA genome into DNA, which is then **integrated into the host genome in the nucleus**, before transcription and translation. - **Cannot replicate in denucleated cells** due to its requirement for nuclear integration. - While it does use **protease cleavage** of polyproteins, the initial steps of DNA synthesis and integration are distinct from the described mechanism. *Measles virus* - Measles is a **negative-sense single-stranded RNA virus**; its genome **cannot be directly translated** into proteins. - It requires an **RNA-dependent RNA polymerase** to synthesize positive-sense mRNA from its genome before protein synthesis can occur. - The question specifies that viral proteins are **directly translated** from the virion's genetic material, which is incompatible with negative-sense RNA viruses. *Molluscum contagiosum virus* - Molluscum contagiosum virus is a **poxvirus**, which is a **double-stranded DNA virus**. - While poxviruses uniquely replicate entirely in the **cytoplasm** and could theoretically work in denucleated cells, they do not use **direct translation** of their genome. - Instead, they employ a complex cascade of gene expression with early, intermediate, and late genes, not the direct genome translation and polyprotein cleavage described in the question.

Question 7: 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.

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.

Question 8: A 44-year-old with a past medical history significant for human immunodeficiency virus infection presents to the emergency department after he was found to be experiencing worsening confusion. The patient was noted to be disoriented by residents and staff at the homeless shelter where he resides. On presentation he reports headache and muscle aches but is unable to provide more information. His temperature is 102.2°F (39°C), blood pressure is 112/71 mmHg, pulse is 115/min, and respirations are 24/min. Knee extension with hips flexed produces significant resistance and pain. A lumbar puncture is performed with the following results: Opening pressure: Normal Fluid color: Clear Cell count: Increased lymphocytes Protein: Slightly elevated Which of the following is the most likely cause of this patient's symptoms?

A. Herpes simplex virus
B. Group B streptococcus
C. Cryptococcus (Correct Answer)
D. Tuberculosis
E. Neisseria meningitidis

Explanation: ***Cryptococcus*** - **Cryptococcus neoformans** is the **most common cause of meningitis** in HIV-positive patients, particularly those with CD4 counts <100 cells/μL. - The CSF findings are **classic for cryptococcal meningitis**: clear fluid, **lymphocytic pleocytosis**, normal or mildly elevated opening pressure, and **slightly elevated protein** with normal or mildly decreased glucose. - The patient's **subacute presentation** with confusion, fever, and meningeal signs in the context of **HIV infection** strongly suggests cryptococcal meningitis as the most likely diagnosis. - Diagnosis is confirmed with **CSF cryptococcal antigen**, India ink stain, or fungal culture. *Herpes simplex virus* - While HSV can cause meningitis or encephalitis, it is **not the most common cause** of meningitis in HIV-positive patients. - **HSV encephalitis** typically presents with more prominent temporal lobe involvement, including personality changes, seizures, and focal neurological deficits. - HSV meningitis is more common in **immunocompetent individuals** and would be less likely than cryptococcal infection in an HIV patient. *Group B streptococcus* - This causes **bacterial meningitis** with a **neutrophilic predominance** in CSF, not lymphocytic. - CSF would show **markedly elevated protein**, **decreased glucose**, and cloudy appearance. - More common in neonates and elderly patients, not typically associated with HIV. *Neisseria meningitidis* - This is a cause of **acute bacterial meningitis** with rapid onset and often a **petechial rash**. - CSF would show **neutrophilic predominance**, **high protein**, **low glucose**, and turbid appearance. - The lymphocytic pleocytosis rules out typical bacterial meningitis. *Tuberculosis* - **Tuberculous (TB) meningitis** is an important consideration in HIV-positive patients and can present with lymphocytic pleocytosis. - However, TB meningitis typically shows **markedly elevated protein** (often >100 mg/dL, not "slightly elevated"), **low glucose** (<45 mg/dL), and may have a "spider-web clot" on standing CSF. - The **more subacute to chronic course** (weeks) and absence of very high protein make TB less likely than cryptococcal meningitis in this acute presentation.

Question 9: A 32-year-old HIV positive male presents to the office complaining of difficulty swallowing and bad breath for the past couple of months. Upon further questioning, he says, "it feels like there’s something in my throat". He says that the difficulty is sometimes severe enough that he has to skip meals. He added that it mainly occurs with solid foods. He is concerned about his bad breath since he has regular meetings with his clients. Although he is on antiretroviral medications, he admits that he is noncompliant. On examination, the patient is cachectic with pale conjunctiva. On lab evaluation, the patient’s CD4+ count is 70/mm3. What is the most likely cause of his symptoms?

A. Candida albicans (Correct Answer)
B. Human papilloma virus
C. Cytomegalovirus
D. HHV-8
E. Irritation due to medication therapy

Explanation: ***Candida albicans*** - The patient's presentation with **dysphagia** (difficulty swallowing), **bad breath**, and sensation of something in the throat, combined with **HIV positive status** and a very **low CD4+ count (70/mm³)**, is highly suggestive of **esophageal candidiasis**. - **Esophageal candidiasis** is a common **opportunistic infection** in immunocompromised individuals, particularly those with advanced HIV (typically CD4+ <100/mm³), and presents with difficulty swallowing (especially solids), halitosis, sensation of food impaction, and can lead to malnutrition and cachexia. *Human papilloma virus* - While **HPV infections** can occur in HIV-positive individuals and cause squamous lesions, they typically manifest as warts or papillomas and are less likely to be the primary cause of such severe, obstructive dysphagia without other characteristic findings. - HPV-related lesions in the esophagus are relatively rare and usually do not present with the specific "something in my throat" sensation or the degree of malnourishment seen in this patient due to diffuse candidal inflammation. *Cytomegalovirus* - **Cytomegalovirus (CMV) esophagitis** is a serious opportunistic infection in HIV patients with very low CD4+ counts (typically <50/mm³), and it can cause dysphagia. - However, CMV esophagitis typically presents with **painful swallowing (odynophagia)** and **linear or deep ulcers** on endoscopy rather than the diffuse inflammation and white plaques characteristic of candidiasis. The patient's presentation of difficulty (not pain) with solids and the "something in the throat" sensation is more typical of candidiasis. *HHV-8* - **Human Herpesvirus 8 (HHV-8)** is primarily associated with **Kaposi's sarcoma (KS)**, which can affect the gastrointestinal tract, including the esophagus. - While KS lesions in the esophagus can cause dysphagia, they are typically described as **purplish, raised lesions**, and the patient's symptoms of bad breath and a feeling of "something in my throat" are not the most common presentation for esophageal Kaposi's sarcoma. *Irritation due to medication therapy* - Although some medications, including certain antiretrovirals, can cause **pill esophagitis** or irritation, the patient's symptoms are chronic ("past couple of months"), severe enough to cause **cachexia**, and his **noncompliance** would make medication-induced irritation less likely to be the sole cause of such severe and prolonged symptoms. - The patient's **compromised immune status** (low CD4+ count) strongly points towards an opportunistic infection rather than merely drug-induced irritation.

Question 10: A 45-year-old man comes to the physician because of a 3-week history of progressive diarrhea and a 2.2-kg (5-lb) weight loss. During the past week, he has had six small bloody stools daily. He is employed as a sales manager and regularly flies to South America. He has HIV, gastroesophageal reflux disease, and hypertension. Current medications include chlorthalidone, omeprazole, emtricitabine, tenofovir, and efavirenz. He reports taking efavirenz irregularly. He is 175 cm (5 ft 9 in) tall and weighs 64 kg (143 lb); BMI is 22 kg/m2. His temperature is 38.1°C (100.6°F), pulse is 91/min, and blood pressure is 116/69 mm Hg. The abdomen is scaphoid. Bowel sounds are normal. His CD4+ T-lymphocyte count is 44/mm3 (N ≥ 500), leukocyte count is 6,000/mm3, and erythrocyte sedimentation rate is 12 mm/h. Colonoscopy shows areas of inflammation scattered throughout the colon with friability, granularity, and shallow linear ulcerations. The intervening mucosa between areas of inflammation appears normal. A biopsy specimen is shown. Which of the following is the most likely cause of this patient's symptoms?

A. Adverse effect of medications
B. Cytomegalovirus (Correct Answer)
C. Clostridioides difficile
D. Cryptosporidium parvum
E. Hepatitis A virus

Explanation: ***Cytomegalovirus*** - The biopsy shows **cytomegalovirus (CMV)** infection, characterized by **intranuclear and intracytoplasmic inclusions** (owl's eye appearance) within endothelial cells, fibroblasts, and macrophages, indicated by the arrows. - This patient's severely **immunocompromised status** (CD4+ count of 44/mm3) makes him highly susceptible to opportunistic infections like CMV, which commonly causes **bloody diarrhea, weight loss**, and scattered colonic inflammation with friability and shallow linear ulcerations. *Adverse effect of medications* - While medications can cause gastrointestinal side effects, the biopsy findings of characteristic **viral inclusions** definitively point away from a drug-induced etiology. - Drug-related diarrhea typically does not present with the specific **histopathological features** seen, particularly the **intranuclear inclusions**. *Clostridioides difficile* - *C. difficile* infection typically presents with **pseudomembranous colitis**, which involves endoscopic findings of raised yellow-white plaques and characteristic pseudomembranes on histology, not the scattered inflammation and specific viral inclusions seen here. - Although the patient is on antibiotics (emtricitabine, tenofovir, efavirenz, though anti-retrovirals are unlikely directly to cause *C. difficile* overgrowth), his CD4 count is far more suggestive of an **opportunistic infection**. *Cryptosporidium parvum* - *Cryptosporidium parvum* causes **watery diarrhea** in immunocompromised individuals and would show **oocysts** on stool examination or small basophilic spheres attached to the brush border of enterocytes on biopsy, not viral inclusions. - It does not typically cause the **bloody diarrhea** or the specific ulcerations observed in this patient. *Hepatitis A virus* - Hepatitis A virus primarily affects the **liver**, causing acute hepatitis with symptoms like fatigue, nausea, vomiting, abdominal pain, and jaundice. - While it can cause some gastrointestinal symptoms, **bloody diarrhea** and the histological findings in the colon are not characteristic of Hepatitis A infection.

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