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?

Decreased negative predictive value

Decreased positive predictive value

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?

It is a qualitative test used for screening purposes.

It is a quantitative test used for screening purposes.

A secondary reagent is needed to interpret the results.

A known antigen binds directly to the patient's serum.

An unknown antigen binds to the known serum.

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?

Vm will decrease, Km will stay the same

Vm will decrease, Km will increase

Vm will stay the same, Km will increase

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?

Antiretroviral therapy during pregnancy and labor

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?

Ring-enhancing lesions on CT imaging

Cotton-wool spots on funduscopic exam

HIV resistance testing for USMLE Step 1: High-Yield Microbiology Lessons

Indications - To Test or Not?

When to Perform Genotype Assay:
- ART-Naïve: At entry into care to guide initial regimen selection.
- Virologic Failure: When viral load rebounds on ART (>200 copies/mL) to guide regimen changes.
- Pregnancy: Before starting ART or if virologic failure occurs.
- Suboptimal viral suppression after starting therapy.
When NOT to Test:
- Not reliable if viral load is <500 copies/mL, as amplification may fail.
- After discontinuing ART, as resistant strains may become undetectable.

⭐ Genotypic assays are the standard for routine testing. Phenotypic assays are reserved for complex cases with extensive resistance, often requiring expert consultation.

HIV resistance development during antiretroviral therapy

Assay Types - Genes vs. Phenes

Feature	Genotypic Assay	Phenotypic Assay
Principle	Detects drug-resistance mutations in viral genes (e.g., pol for RT, PR, IN).	Measures viral replication in the presence of antiretroviral drugs.
Method	Sanger or Next-Generation Sequencing of viral RNA.	Recombinant virus culture with drug titration.
Turnaround	Faster: 1-2 weeks.	Slower: 2-4 weeks.
Cost	Lower.	Higher.
Sensitivity	Requires viral load >500-1000 copies/mL. Can detect minor variants.	Requires viral load >1000 copies/mL. Less sensitive to minor variants.
Utility	Standard for initial testing; infers resistance from known mutations.	"Gold standard" for complex cases; directly measures drug susceptibility.

⭐ Exam Favorite: Genotypic testing is the preferred method for initial resistance assessment in treatment-naïve patients and for initial virologic failure due to its speed and lower cost. Phenotypic tests are reserved for complex cases with extensive treatment history.

Interpreting Reports - Decoding Mutations

Genotypic reports identify specific amino acid substitutions in viral genes (e.g., pol).
Mutation nomenclature: M184V = Methionine (M) at position 184 is replaced by Valine (V).
Interpretation relies on databases (e.g., Stanford HIVDB) to correlate mutations with drug resistance levels.
Key Resistance Mutations by Class:
- NRTIs: M184V (major 3TC/FTC resistance), K65R (broad NRTI resistance), Thymidine Analogue Mutations (TAMs).
- NNRTIs: K103N (class-wide resistance), Y181C, G190A.
- Protease Inhibitors (PIs): L90M, I84V (major mutations).
- Integrase Inhibitors (INSTIs): N155H, Q148H/R/K.

⭐ The M184V mutation, while conferring high-level resistance to Lamivudine/Emtricitabine, impairs viral replication and can paradoxically increase susceptibility to Tenofovir and Zidovudine.

HIV resistance testing is crucial at entry into care and upon virologic failure to guide antiretroviral therapy (ART).

Genotypic assays, the standard initial test, detect resistance-conferring mutations in the pol gene (reverse transcriptase, protease, integrase).

They are faster and cheaper than phenotypic tests but require expert interpretation.

Phenotypic assays measure the concentration of a drug needed to inhibit viral growth, directly assessing resistance.

Phenotyping is reserved for complex resistance patterns or after failure of multiple ART regimens.

Tests may not detect minority resistance variants present at <20% of the viral population.

Continue reading on Oncourse

CONTINUE READING — FREE

or get the app

App Store|Google Play