HIV

HIV 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 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 US Medical PG Question 2: A 2300-g (5-lb 1-oz) male newborn is delivered to a 29-year-old primigravid woman. The mother has HIV and received triple antiretroviral therapy during pregnancy. Her HIV viral load was 678 copies/mL 1 week prior to delivery. Labor was uncomplicated. Apgar scores are 7 and 8 at 1 and 5 minutes respectively. Physical examination of the newborn shows no abnormalities. Which of the following is the most appropriate next step in management of this infant?

• A. Administer lamivudine and nevirapine
• B. Administer zidovudine, lamivudine and nevirapine (Correct Answer)
• C. Administer nevirapine
• D. Administer zidovudine
• E. HIV antibody testing

HIV Explanation: ***Administer zidovudine, lamivudine and nevirapine*** - The mother has a **viral load of 678 copies/mL**, which falls into the **intermediate-risk category** (50-999 copies/mL) for HIV transmission. - Current guidelines recommend **combination antiretroviral prophylaxis** (zidovudine + lamivudine + nevirapine) for infants born to mothers with viral loads in this range, typically given for 2 weeks followed by zidovudine alone to complete 4-6 weeks. - This enhanced regimen provides better protection than monotherapy when maternal viral suppression is suboptimal. *Administer zidovudine* - Zidovudine monotherapy is reserved for **low-risk infants** whose mothers have viral loads **<50 copies/mL** at delivery with documented adherence to ART during pregnancy. - With a maternal viral load of 678 copies/mL, monotherapy alone is **insufficient** and would not meet current standard of care for HIV prophylaxis. *Administer lamivudine and nevirapine* - This regimen omits **zidovudine**, which remains the **backbone of neonatal HIV prophylaxis** and should always be included. - Using only lamivudine and nevirapine without zidovudine is not consistent with established guidelines. *Administer nevirapine* - Nevirapine monotherapy is **not adequate** for HIV prophylaxis in developed countries with access to combination therapy. - While nevirapine may be used as a single dose in resource-limited settings, it should be part of a multi-drug regimen when other agents are available. *HIV antibody testing* - HIV antibody testing in newborns will detect **maternal antibodies** that crossed the placenta and cannot determine the infant's true infection status at birth. - While HIV diagnostic testing using **PCR or viral load assays** will be performed at 14-21 days, 1-2 months, and 4-6 months of age, **antiretroviral prophylaxis must be initiated immediately** after birth to prevent transmission.

HIV US Medical PG Question 3: A 45-year-old man with a history of poorly controlled human immunodeficiency virus (HIV) infection presents to the emergency room complaining of clumsiness and weakness. He reports a 3-month history of worsening balance, asymmetric muscle weakness, and speech difficulties. He recently returned from a trip to Guatemala to visit his family. He has been poorly compliant with his anti-retroviral therapy and his most recent CD4 count was 195. His history is also notable for rheumatoid arthritis and hepatitis C. His temperature is 99°F (37.2°C), blood pressure is 140/90 mmHg, pulse is 95/min, and respirations are 18/min. On exam, he has 4/5 strength in his right upper extremity, 5/5 strength in his left upper extremity, 5/5 strength in his right lower extremity, and 3/5 strength in his left lower extremity. His speech is disjointed with intermittent long pauses between words. Vision is 20/100 in the left eye and 20/40 in his right eye; previously, his eyesight was 20/30 bilaterally. This patient most likely has a condition caused by which of the following types of pathogens?

• A. Arenavirus
• B. Bunyavirus
• C. Herpesvirus
• D. Polyomavirus (Correct Answer)
• E. Picornavirus

HIV Explanation: ***Polyomavirus*** - The patient's **poorly controlled HIV**, **low CD4 count (195)**, and progressive neurological symptoms (clumsiness, weakness, speech difficulties, vision changes) are highly suggestive of **Progressive Multifocal Leukoencephalopathy (PML)**. - PML is caused by the **JC virus**, which is a type of **polyomavirus**, typically reactivating in immunocompromised individuals. *Arenavirus* - Arenaviruses (e.g., Lassa fever virus) are known to cause **hemorrhagic fevers** and can lead to neurological complications, but the clinical presentation described (progressive focal neurological deficits in an HIV patient) is not typical for an arenavirus infection. - While some arenaviruses cause **meningoencephalitis**, the progressive, demyelinating-like course seen in this patient points away from arenavirus. *Bunyavirus* - Bunyaviruses (e.g., Hantavirus, La Crosse encephalitis virus) can cause **encephalitis**, fever, and myalgia, but they don't typically present with the specific constellation of **progressive white matter lesions** and focal neurological signs characteristic of PML in an HIV patient. - Hantaviruses are more associated with **hemorrhagic fever with renal syndrome** or **hantavirus cardiopulmonary syndrome**. *Herpesvirus* - While herpesviruses (e.g., HSV, CMV, VZV) can cause severe neurological disease in HIV patients (e.g., **CMV encephalitis**, **HSV encephalitis**, **VZV vasculopathy**), the described progressive multifocal deficits, especially with rapid worsening, in an HIV patient with a low CD4 count strongly favor PML. - Herpesviral encephalitides often present with more acute onset, fever, and seizures, or specific radiographic patterns not directly matching PML. *Picornavirus* - Picornaviruses, such as enteroviruses, can cause **aseptic meningitis** or **encephalitis**, particularly in immunocompromised individuals. - However, the progressive, multifocal neurological deficits, particularly affecting **white matter**, are not characteristic of picornavirus infections, which tend to cause more diffuse or acute inflammatory processes.

HIV US Medical PG Question 4: A 46-year-old Caucasian male with past medical history of HIV (CD4: 77/mm^3), hypertension, hyperlipidemia, and osteoarthritis presents to the emergency department with sudden weakness of his right hand. He reports that the weakness has gradually been getting worse and that this morning he dropped his cup of coffee. He has never had anything like this happen to him before, although he was hospitalized last year for pneumonia. He reports inconsistent adherence to his home medications, which include raltegravir, tenofovir, emtricitabine, TMP-SMX, hydrochlorothiazide, pravastatin, and occasional ibuprofen. His father died of a myocardial infarction at the age of 60, and his mother suffered a stroke at the age of 72. The patient's temperature is 102.6°F (39.2°C), blood pressure is 156/92 mmHg, pulse is 88/min, and respirations are 18/min. On neurological exam, he has 3/5 strength in the distal muscles of the right extremity with preserved sensation. His neurological exam is normal in all other extremities. Which of the following is the best next step in management?

• A. Serology for Toxoplasma-specific IgG antibodies
• B. Empiric treatment with pyrimethamine-sulfadiazine
• C. Head CT (Correct Answer)
• D. Empiric treatment with itraconazole
• E. Lumbar puncture

HIV Explanation: ***Head CT*** - The patient presents with **focal neurological deficits** (right hand weakness) and has several risk factors, including poorly controlled **HIV with a low CD4 count** (increased risk of opportunistic infections or CNS lesions) and uncontrolled hypertension (increased risk of stroke). A **head CT** is crucial to rapidly identify potential causes like a mass lesion, hemorrhage, or infarct, which would guide immediate management. - The **fever** and **subacute onset** of weakness (gradually worsening with acute exacerbation) also point towards an intracranial process that needs urgent imaging. *Serology for Toxoplasma-specific IgG antibodies* - While **Toxoplasmosis** is a strong consideration given the patient's low CD4 count, **serology alone is not the best initial step** for acute neurological deficits. - A positive IgG indicates past exposure but not necessarily active infection, and it doesn't provide real-time information on the cause of the focal neurological symptoms. Imaging is needed first to identify a lesion. *Empiric treatment with pyrimethamine-sulfadiazine* - This is the treatment for **cerebral toxoplasmosis**, but **empiric treatment should only be initiated after imaging** (CT or MRI) confirms the presence of a lesion consistent with toxoplasmosis, especially in a patient with acute focal deficits. - Starting treatment without imaging may delay diagnosis of other potentially critical conditions like a brain abscess, lymphoma, or stroke. *Empiric treatment with itraconazole* - **Itraconazole** is an antifungal medication, typically used for histoplasmosis, blastomycosis, or aspergillosis, which are less common causes of acute focal neurological deficits in HIV than toxoplasmosis or lymphoma. - There is no specific clinical indication or risk factor (e.g., endemic area for fungal infections) that would make **empiric antifungal treatment** the best next step compared to diagnostic imaging for this presentation. *Lumbar puncture* - A **lumbar puncture** can be useful in diagnosing CNS infections (e.g., cryptococcal meningitis, viral encephalitis) or other inflammatory conditions, but it is typically performed *after* ruling out a mass lesion or increased intracranial pressure with imaging (CT or MRI) to prevent herniation. - Given the patient's focal neurological deficit and potential for a mass or hemorrhage, **LP carries a risk of brain herniation** and is not the best initial step.

HIV US Medical PG Question 5: A physician scientist is looking for a more efficient way to treat HIV. Patients infected with HIV mount a humoral immune response by producing antibodies against the HIV envelope proteins. These antibodies are the same antibodies detected by the ELISA and western blot assays used to diagnose the disease. The physician scientist is trying to generate a new, more potent antibody against the same HIV envelope proteins targeted by the natural humoral immune response. Of the following proteins, which is the most likely target of the antibody he is designing?

• A. p24
• B. CXCR4
• C. CCR5
• D. p17
• E. gp120 (Correct Answer)

HIV Explanation: ***gp120*** - **gp120** is an **envelope glycoprotein** on the surface of HIV, responsible for binding to CD4 receptors on host cells. - Antibodies against **gp120** are generated during natural infection and are detected by diagnostic assays, making it a primary target for therapeutic antibody development. *p24* - **p24** is a **capsid protein** of HIV, forming the conical core of the virus, but it is not an envelope protein. - While antibodies against **p24** are produced during infection and are detectable, it's an internal protein, not exposed on the viral surface for direct neutralization. *CXCR4* - **CXCR4** is a **chemokine co-receptor** found on the surface of host cells (e.g., T-lymphocytes), used by some HIV strains (T-tropic) for entry. - It is a host cell protein, not an HIV viral protein, so it would not be a target for antibodies aiming to directly neutralize the virus. *CCR5* - **CCR5** is another **chemokine co-receptor** on host cells (e.g., macrophages, T-lymphocytes) used by other HIV strains (M-tropic) for viral entry. - Similar to CXCR4, it is a host cell protein, not an HIV envelope protein, and therefore not a direct target for neutralizing antibodies against the virus itself. *p17* - **p17** is an HIV **matrix protein** located just beneath the viral envelope, playing a role in viral assembly and budding. - Similar to p24, it is an internal structural protein, not an external envelope protein, making it less accessible for neutralizing antibodies.

HIV US Medical PG Question 6: 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

HIV 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.

HIV US Medical PG Question 7: A 28-year-old G1P0 woman at 16 weeks estimated gestational age presents for prenatal care. Routine prenatal screening tests are performed and reveal a positive HIV antibody test. The patient is extremely concerned about the possible transmission of HIV to her baby and wants to have the baby tested as soon as possible after delivery. Which of the following would be the most appropriate diagnostic test to address this patient’s concern?

• A. CD4+ T cell count
• B. Viral culture
• C. Polymerase chain reaction (PCR) for HIV RNA (Correct Answer)
• D. Antigen assay for p24
• E. EIA for HIV antibody

HIV Explanation: ***Polymerase chain reaction (PCR) for HIV RNA*** - **PCR for HIV RNA** directly detects the viral genetic material, providing a definitive diagnosis of HIV infection in an infant. - Unlike antibody tests, PCR can distinguish between passively acquired maternal antibodies and actual infant infection, making it suitable for newborns. *CD4+ T cell count* - **CD4+ T cell count** is used to monitor the progression of HIV infection and immunosuppression, not for initial diagnosis, especially in neonates. - While it's an important marker for HIV disease, it does not confirm the presence of the virus itself in a newborn. *Viral culture* - **Viral culture** is a highly specific method for detecting HIV, but it is expensive, time-consuming, and technically demanding. - It is not routinely used for rapid early diagnosis in neonates due to its practical limitations and the availability of faster, reliable alternatives like PCR. *Antigen assay for p24* - The **p24 antigen test** can detect early HIV infection in adults, but its sensitivity is lower in neonates compared to PCR, especially immediately after birth. - It may not reliably detect infection in newborns due to low viral loads or the presence of maternal antibodies that complex the antigen. *EIA for HIV antibody* - An **EIA for HIV antibody** will detect maternal antibodies that have crossed the placenta, meaning it will be positive in nearly all infants born to HIV-positive mothers, regardless of the infant's infection status. - This test cannot distinguish between passive maternal antibody transfer and true infant infection.

HIV US Medical PG Question 8: A 33-year-old man is brought into the emergency department with fever, lethargy, and confusion. He is a cachectic man in acute distress, unable to respond to questions or follow commands. His friend confides that the patient has been sexually active with multiple male partners and was diagnosed with HIV several months ago, but was lost to follow up. Based on prior records, his most recent CD4 count was 65 cells/uL. Which of the following is the most appropriate next step in management?

• A. CT head without contrast (Correct Answer)
• B. Lumbar puncture
• C. Recheck CD4 and HIV viral load serologies
• D. MRI brain with contrast
• E. Neurological exam with fundoscopy

HIV Explanation: ***CT head without contrast*** - With signs of **increased intracranial pressure** (lethargy, confusion, inability to follow commands), performing a non-contrast CT head is crucial to rule out a **mass lesion** or **herniation risk** before any invasive procedures like a lumbar puncture. - This patient's severely low **CD4 count** (65 cells/uL) puts him at very high risk for opportunistic central nervous system infections such as **toxoplasmosis** or **PML**, or even CNS lymphoma, which can cause mass lesions. *Lumbar puncture* - A **lumbar puncture** is contraindicated in the presence of signs suggestive of increased intracranial pressure until a **mass lesion** has been excluded by imaging. - Performing a lumbar puncture in such a situation could precipitate **brain herniation**, which can be fatal. *Recheck CD4 and HIV viral load serologies* - While important for long-term management, rechecking these labs is not the most **immediate next step** for an acutely ill patient with severe neurological symptoms. - The patient requires urgent diagnosis and treatment for his acute condition, which could be life-threatening, before focusing on **baseline serologies**. *MRI brain with contrast* - An **MRI brain with contrast** provides more detailed imaging than a CT, but a non-contrast CT is faster and sufficient for initial screening for mass lesions or herniation risk. - In an emergency setting with an unstable patient, the **rapid accessibility** of CT makes it the preferred initial imaging modality. *Neurological exam with fundoscopy* - A neurological exam and fundoscopy are important components of the work-up but are **diagnostic steps**, not a management step. - These exams will help localize the lesion and assess for **papilledema**, but imaging is required to confirm the presence of a mass or rule out herniation risk.

HIV US Medical PG Question 9: A 27-year-old man presents with a 2-week history of fever, malaise, and occasional diarrhea. On physical examination, the physician notes enlarged inguinal lymph nodes. An HIV screening test is positive. Laboratory studies show a CD4+ count of 650/mm3. This patient is most likely currently in which of the following stages of HIV infection?

• A. Chronic HIV infection
• B. Asymptomatic HIV infection
• C. AIDS
• D. Acute HIV infection (Correct Answer)
• E. Clinical latency stage

HIV Explanation: ***Acute HIV infection*** - The symptoms (fever, malaise, diarrhea, enlarged lymph nodes) and the timeframe (2 weeks) are classic for **acute retroviral syndrome**, which occurs 2-4 weeks after initial HIV infection. - A positive HIV screening test with a relatively high **CD4+ count** (650/mm³) is typical during this initial phase before significant immune deterioration. - Also known as **primary HIV infection**, this stage represents the body's initial immune response to the virus. *Chronic HIV infection* - This stage is typically characterized by a **longer duration** (years) with often **asymptomatic periods** or mild, non-specific symptoms, and a gradually declining CD4+ count. - While enlarged lymph nodes can persist, the acute onset of fever and malaise with only 2 weeks of symptoms points away from this more stable, quiescent phase. *Asymptomatic HIV infection* - This phrase is often used interchangeably with the **clinical latency stage** of chronic HIV infection, where the patient has no symptoms related to HIV despite ongoing viral replication. - The presence of fever, malaise, diarrhea, and lymphadenopathy described in the case clearly indicates a **symptomatic phase**, not an asymptomatic one. *AIDS* - **AIDS (Acquired Immunodeficiency Syndrome)** is defined by a CD4+ T cell count below 200 cells/mm³ or the presence of an AIDS-defining opportunistic infection or malignancy. - The patient's CD4+ count of 650/mm³ is well above the threshold for AIDS diagnosis. *Clinical latency stage* - This stage, also called **chronic asymptomatic HIV infection**, typically lasts 8-10 years without treatment and is characterized by minimal or no symptoms. - Patients in clinical latency have **declining but not yet critically low CD4+ counts** and generally feel well. - The acute presentation with fever, malaise, and the **2-week timeframe** clearly indicates a much earlier stage of infection.

HIV US Medical PG Question 10: 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 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 Flashcard 1 of 10

Question: HIV initially infects what cell type?_____

Answer: Macrophages

HIV Flashcard 2 of 10

Question: Which gene is mutated in HIV protease inhibitor resistance?_____

Answer: pol gene

HIV Flashcard 3 of 10

Question: Which two regulatory proteins of HIV are required for viral replication?_____

Answer: Rev and Tat

HIV Flashcard 4 of 10

Question: What infectious disease is an irreversible cause of dementia? _____

Answer: HIV

HIV Flashcard 5 of 10

Question: HIV later on infects what cell type?_____

Answer: CD4+ Helper T cells

HIV Flashcard 6 of 10

Question: Which viral gene in HIV codes for the p24 capsid protein?_____

Answer: gag

HIV Flashcard 7 of 10

Question: Does HIV have an envelope?_____

Answer: Yes

HIV Flashcard 8 of 10

Question: progressive multifocal leukoencephalopathy (PML)

Answer:

Extra Information: destruction of oligodendrocytes, demyelination of CNSrapidly progressive, usually fatalrecent JC virus infection, AIDS

HIV Flashcard 9 of 10

Question: The _____ blot *used to be* the confirmatory test for HIV after a positive ELISA

Answer: Western

Extra Information:   https://onlinemeded.org/spa/infectious-disease/hiv/acquire?ref=anki 

HIV Flashcard 10 of 10

Question: Which HIV gene encodes for the virion p24 (Capsid) and p17 (Matrix) core proteins? _____

Answer: gag

Extra Information:    https://onlinemeded.org/spa/microbiology/antivirals/acquire?ref=anki