USMLE Step 1 Quiz
Practice Hiv And Retroviruses in USMLE Step 1 with focused quiz questions that help you check what you know, review explanations, and build confidence with test-style prompts.
Question 1 / 20
0 of 20 answered
A 25-year-old woman is diagnosed with HIV infection during a routine prenatal screening. She is started on combination antiretroviral therapy (cART) that includes tenofovir. This drug is a nucleotide reverse transcriptase inhibitor (NRTI).
Which of the following processes is directly inhibited by the active form of tenofovir?
This quiz focuses on Hiv And Retroviruses, giving you a quick way to practice the rules, question types, and explanations that matter most for USMLE Step 1.
Try each quiz question before looking at the correct answer. Use the explanations to review missed ideas, then come back to similar questions until the pattern feels familiar.
A 25-year-old woman is diagnosed with HIV infection during a routine prenatal screening. She is started on combination antiretroviral therapy (cART) that includes tenofovir. This drug is a nucleotide reverse transcriptase inhibitor (NRTI).
Which of the following processes is directly inhibited by the active form of tenofovir?
Explanation: Tenofovir is a nucleotide reverse transcriptase inhibitor (NRTI). After phosphorylation to its active form (tenofovir diphosphate), it competes with deoxyadenosine triphosphate for incorporation into the growing DNA chain by the viral reverse transcriptase. Because it lacks a 3'-hydroxyl group, its incorporation results in chain termination, thus inhibiting the synthesis of double-stranded proviral DNA from the viral RNA template.
A 35-year-old woman with advanced AIDS and a CD4 count of 45 cells/mm³ is hospitalized with Pneumocystis pneumonia. Her physician explains that the virus responsible for her condition must first attach to and fuse with her immune cells to replicate.
The conformational change required for the fusion of the HIV envelope with the host cell membrane is mediated by which of the following viral proteins?
Explanation: HIV entry is a two-step process involving two envelope glycoproteins. First, the surface glycoprotein gp120 binds to the CD4 receptor and a coreceptor (CCR5 or CXCR4). This binding event induces a conformational change that exposes the transmembrane glycoprotein gp41. The newly exposed gp41 protein then inserts into the host cell membrane and refolds, pulling the viral and host membranes together and mediating their fusion. p24 is the capsid protein, and p17 is the matrix protein.
A researcher is studying the structure of the HIV-1 provirus after it has been integrated into a host T-cell's genome. The provirus contains long terminal repeats (LTRs) at each end, which are identical nucleotide sequences.
The LTRs of the integrated HIV provirus contain regulatory sequences that serve as a binding site for which of the following?
Explanation: The long terminal repeats (LTRs) are created during reverse transcription and are found at both ends of the integrated provirus. The 5' LTR acts as a powerful promoter for viral gene expression. It contains binding sites for host cell transcription factors, such as NF-κB and Sp1, as well as for the viral Tat protein. The activation state of the T-cell influences the availability of these transcription factors, which in turn regulates the transcription of the proviral DNA by the host's RNA polymerase II.
A 34-year-old woman with untreated HIV infection is brought to the emergency department after a generalized tonic-clonic seizure. An MRI of the brain reveals multiple ring-enhancing lesions. A serologic test for Toxoplasma gondii IgG is positive. Her CD4 count is 75 cells/mm³.
The development of toxoplasmic encephalitis in this patient is primarily due to the loss of which of the following immune functions?
Explanation: Control of latent Toxoplasma gondii infection relies heavily on cell-mediated immunity. CD4+ T-helper cells, specifically the Th1 subset, are critical for this process. Th1 cells produce interferon-gamma (IFN-γ), which is the principal cytokine responsible for activating macrophages to kill intracellular tachyzoites. With a CD4 count of 75 cells/mm³, this patient has a profound defect in Th1 function, allowing for the reactivation of latent toxoplasmosis and the development of encephalitis.
A 50-year-old man with HIV is being treated with a combination antiretroviral therapy that includes atazanavir, a protease inhibitor. He is also being treated for hyperlipidemia with simvastatin. His physician cautions him about a potential drug-drug interaction that could increase the risk of myopathy.
This interaction occurs because atazanavir inhibits which of the following host systems, leading to increased levels of simvastatin?
Explanation: Most HIV protease inhibitors, including atazanavir, are potent inhibitors of the cytochrome P450 system, particularly the CYP3A4 isoenzyme. Simvastatin and many other statins are extensively metabolized by CYP3A4. Co-administration of a protease inhibitor with simvastatin can block its metabolism, leading to significantly increased plasma concentrations and a heightened risk of dose-dependent adverse effects like myopathy and rhabdomyolysis.
A 30-year-old man with a history of intravenous drug use presents with a 2-week history of fever, sore throat, and a maculopapular rash. A 4th-generation HIV test is positive. A new antiviral agent, maraviroc, is being considered. This drug prevents the virus from entering host cells by binding to a host cell surface protein.
Maraviroc exerts its therapeutic effect by blocking the interaction between the viral envelope protein gp120 and which of the following host cell proteins?
Explanation: Maraviroc is a CCR5 antagonist, also known as an entry inhibitor. It blocks the binding of the HIV gp120 protein to the CCR5 coreceptor. This interaction is a necessary step for the entry of macrophage-tropic (M-tropic) HIV strains, which are typically dominant in early infection. By blocking this coreceptor, maraviroc prevents the virus from entering host cells like macrophages and CD4+ T-cells.
A 42-year-old man with a long-standing HIV infection has been non-adherent to his medication regimen. His viral load has increased significantly. He is started on a new regimen that includes raltegravir. After 3 months, his viral load becomes undetectable.
The efficacy of raltegravir is due to its ability to prevent which of the following steps in the HIV replication cycle?
Explanation: Raltegravir is an integrase strand transfer inhibitor (INSTI). It binds to and inhibits the viral enzyme integrase, which is responsible for covalently inserting the proviral DNA (synthesized by reverse transcriptase) into the host cell's chromosome. This step is critical for establishing a permanent, latent infection. By blocking integration, raltegravir effectively halts the viral replication cycle.
A research laboratory is developing a novel antiretroviral agent. The compound is found to be effective in cell culture. Treatment results in the release of viral particles from infected cells, but these particles are non-infectious and have a distinct, immature morphology on electron microscopy.
The viral enzyme most likely targeted by this new agent is which of the following?
Explanation: HIV protease is a viral enzyme essential for the late stages of replication. It cleaves the Gag and Gag-Pol polyproteins into their individual functional components (e.g., p24 capsid, p17 matrix, reverse transcriptase, integrase). Inhibition of protease prevents this maturation step. As a result, immature, non-infectious virions are assembled and released from the cell, effectively stopping the spread of the virus.
A 28-year-old healthcare worker sustains a needlestick injury from a patient with a known high HIV viral load. The worker undergoes post-exposure prophylaxis and serial testing. Four weeks after the exposure, a 4th generation HIV test is performed. This test combines an immunoassay for HIV-1/HIV-2 antibodies with detection of a specific viral antigen.
Detection of which of the following viral proteins allows for earlier diagnosis of acute HIV infection compared to antibody-only tests?
Explanation: The p24 protein is the viral capsid protein, a core component of the HIV virion. It is produced in large quantities during the initial burst of viral replication in acute infection. p24 antigen can be detected in the blood as early as 10-14 days post-infection, before the development of detectable anti-HIV antibodies. Fourth-generation assays detect both p24 antigen and HIV antibodies, shortening the diagnostic 'window period' compared to older antibody-only tests.
In a clinical trial for a new HIV vaccine, researchers observe that some individuals who become infected initially have a viral strain that infects macrophages. Over time, the virus evolves and begins to preferentially infect naive T-lymphocytes, which is associated with a more rapid decline in CD4 count.
This change in viral tropism is most likely due to a mutation in the viral env gene that alters the binding affinity for which of the following host cell surface molecules?
Explanation: HIV tropism is determined by the coreceptor it uses in addition to CD4. Macrophage-tropic (M-tropic or R5) strains use the CCR5 coreceptor, found on macrophages, dendritic cells, and memory T cells. T-cell-tropic (T-tropic or X4) strains use the CXCR4 coreceptor, found primarily on naive T-lymphocytes. A switch from CCR5 to CXCR4 usage (a 'tropism switch') often occurs late in disease and is associated with accelerated CD4+ T-cell depletion and disease progression.
A 45-year-old woman with HIV has been on a stable antiretroviral regimen for several years. Her regimen includes emtricitabine. Laboratory tests show signs of mitochondrial toxicity, including a mild, persistent lactic acidosis.
The toxicity observed in this patient is related to the off-target inhibition of which of the following host enzymes by emtricitabine?
Explanation: Emtricitabine is a nucleoside reverse transcriptase inhibitor (NRTI). The primary mechanism of toxicity for the NRTI class is the inhibition of mitochondrial DNA polymerase gamma. This host enzyme is responsible for replicating mitochondrial DNA. Inhibition leads to mitochondrial dysfunction, impaired oxidative phosphorylation, and consequent adverse effects such as lactic acidosis, pancreatitis, and peripheral neuropathy.
A 29-year-old pregnant woman is diagnosed with HIV at 12 weeks gestation. She is started on a three-drug antiretroviral regimen containing dolutegravir. The goal of therapy is to rapidly suppress her viral load to prevent vertical transmission.
Dolutegravir effectively suppresses viral replication by inhibiting the enzyme responsible for which of the following functions?
Explanation: Dolutegravir is an integrase strand transfer inhibitor (INSTI). The viral enzyme integrase is responsible for inserting the reverse-transcribed viral DNA (provirus) into the host cell's genome by covalently linking it to the host DNA. By inhibiting this enzyme, dolutegravir prevents the establishment of a permanent, latent infection within the host cell, thus halting the replication cycle. Option B describes reverse transcriptase, C describes gp41, and D describes protease.
A 22-year-old man presents to an urgent care clinic with a 5-day history of fever, fatigue, pharyngitis, and a diffuse maculopapular rash. He reports a new sexual partner 3 weeks ago. Physical examination reveals cervical lymphadenopathy. Laboratory studies show a high viral load and a negative HIV-1/2 antibody test, but a positive p24 antigen test.
This patient's clinical presentation is most consistent with which of the following stages of HIV infection?
Explanation: The patient is presenting with a mononucleosis-like illness approximately 2-4 weeks after a potential exposure. This constellation of symptoms (fever, fatigue, pharyngitis, lymphadenopathy, rash) is characteristic of acute retroviral syndrome. The laboratory findings of a high viral load with a negative antibody test but positive p24 antigen test confirm an acute infection within the 'window period' before antibodies have fully developed. Clinical latency is asymptomatic, and AIDS involves severe immunodeficiency.
A 38-year-old man with untreated HIV infection has a CD4+ T-cell count that has progressively declined from 600 cells/mm³ to 250 cells/mm³ over the past five years. A significant proportion of the depleted CD4+ T-cells are found to be uninfected 'bystander' cells.
Which of the following is a major mechanism contributing to the depletion of uninfected CD4+ T-cells in chronic HIV infection?
Explanation: While direct viral killing of infected cells occurs, a major contributor to CD4+ T-cell depletion, especially of uninfected 'bystander' cells, is apoptosis. Chronic immune activation caused by HIV leads to increased expression of pro-apoptotic molecules like Fas (CD95) and Fas-ligand on T-cells. This renders both infected and uninfected activated T-cells highly susceptible to activation-induced cell death, contributing significantly to lymphopenia.
A 46-year-old woman with a history of intravenous drug use presents with a 1-month history of progressive dyspnea and a dry cough. A chest X-ray shows diffuse bilateral interstitial infiltrates. A bronchoalveolar lavage is positive for Pneumocystis jirovecii.
Based on this opportunistic infection, this patient's CD4+ T-lymphocyte count is most likely below which of the following thresholds?
Explanation: The presence of an AIDS-defining illness, such as Pneumocystis jirovecii pneumonia (PJP), is sufficient for a diagnosis of AIDS. PJP typically occurs when the CD4+ T-cell count falls below 200 cells/mm³. This level of immunosuppression severely impairs cell-mediated immunity, which is crucial for controlling this opportunistic fungus. Prophylaxis for PJP is recommended for all HIV-infected individuals with a CD4 count below this threshold.
A 52-year-old man with AIDS, who is non-adherent to his antiretroviral therapy, presents with a 3-week history of fever, night sweats, weight loss, and diarrhea. His last recorded CD4 count was 30 cells/mm³. Blood cultures are performed and eventually grow an acid-fast bacillus.
The pathogen responsible for this patient's disseminated disease is most likely which of the following?
Explanation: Disseminated Mycobacterium avium complex (MAC) infection is a common opportunistic infection in patients with advanced AIDS, typically occurring when the CD4 count drops below 50 cells/mm³. The clinical presentation of systemic symptoms like fever, night sweats, weight loss, and diarrhea is classic for disseminated MAC. While M. tuberculosis can occur at any CD4 count, it is more common at higher counts than MAC.
A 41-year-old man with untreated HIV infection presents with several painless, purplish, non-blanching nodules on his arms and hard palate. A biopsy of a skin lesion reveals spindle-shaped cells, neovascularization, and extravasated red blood cells.
This patient's condition is caused by an infection with which of the following viruses?
Explanation: The clinical and histologic findings are classic for Kaposi sarcoma (KS). KS is an AIDS-defining malignancy caused by Human herpesvirus 8 (HHV-8). The virus infects endothelial cells and induces their proliferation and angiogenesis, driven by viral proteins that mimic host growth factors. The severe immunodeficiency of AIDS allows for uncontrolled HHV-8 replication and the development of KS.
A 24-year-old man comes to the clinic requesting HIV testing. He is concerned because he had unprotected sex 10 days ago. A rapid antibody-only test is negative. The physician explains that this result may not be conclusive due to the 'window period.'
The most appropriate next test to diagnose an acute infection in this patient would be one that detects which of the following?
Explanation: The window period is the time between initial infection and the development of detectable antibodies. During this period, the virus is actively replicating. The first marker to become detectable is viral RNA, which can be measured by a nucleic acid amplification test (NAAT). HIV RNA is typically detectable within 7-14 days of infection, making it the most sensitive test for diagnosing acute HIV. A 4th-generation antigen/antibody test would also be appropriate, but HIV RNA is the earliest marker.
Researchers are studying the long-term immune response in a cohort of 'elite controllers,' individuals who maintain undetectable viral loads without antiretroviral therapy. They note that a key challenge for the humoral immune system is the rapid mutation rate of one specific viral gene, leading to immune escape.
Mutations in the gene encoding which of the following proteins are most responsible for HIV's ability to evade the neutralizing antibody response?
Explanation: The env gene encodes the envelope glycoproteins gp120 and gp41, which are displayed on the surface of the virion and are the primary targets for neutralizing antibodies. The viral reverse transcriptase is highly error-prone, leading to a high mutation rate. Mutations in the env gene are particularly significant because they alter the structure of gp120, allowing the virus to escape recognition by pre-existing antibodies. This constant evolution is a major obstacle to vaccine development.
An experimental HIV therapy is designed to inhibit the function of the Tat protein. In cell culture, this therapy successfully reduces the production of new viral particles from latently infected cells that have been reactivated.
The Tat protein enhances viral production by performing which of the following functions?
Explanation: Tat stands for 'Trans-Activator of Transcription.' It is a regulatory protein that binds to a specific RNA sequence called the TAR (trans-activation response) element, located at the 5' end of all viral transcripts. This binding significantly increases the processivity of the host RNA polymerase II, preventing premature termination and promoting the synthesis of full-length viral mRNAs. This creates a powerful positive feedback loop, leading to a massive amplification of viral gene expression.