Infectious Diseases Module 6

A 32-year-old man presents to a sexual health clinic 3 weeks after a high-risk sexual encounter with a febrile illness, sore throat, maculopapular rash and cervical lymphadenopathy. His investigations reveal:

• HIV Ag/Ab combination immunoassay: reactive
• HIV RNA viral load: 850,000 copies/mL
• CD4 count: 480 cells/µL (reference range 500–1500 cells/µL)
• HIV genotypic tropism assay: R5-tropic virus

The virus responsible for this patient’s infection requires binding to CD4 and a co-receptor to gain entry into host cells.

Which of the following cell surface molecules is the co-receptor most likely utilised during this early phase of infection?

A 26-year-old woman presents 10 days after a condom failure with an anxious desire for HIV testing. She is asymptomatic. A fourth-generation HIV Ag/Ab combination immunoassay is negative.

She is very concerned as her partner is known to be HIV positive with a detectable viral load.

Which of the following investigations is most appropriate to exclude acute HIV infection at this stage?

A 44-year-old man is referred after an incidental positive HIV diagnosis made during a routine insurance screen. He reports no symptoms and states he has never been unwell. He is not on antiretroviral therapy.

Investigations reveal:

• HIV RNA viral load: <50 copies/mL (undetectable, off treatment)
• CD4 count: 920 cells/µL (reference range 500–1500 cells/µL)
• HLA typing: HLA-B*57:01 positive
• Estimated duration of infection: >8 years

Which of the following best explains this patient’s ability to control viraemia in the absence of treatment?

A 38-year-old woman with well-controlled HIV enrolled in a clinical trial evaluating dual broadly neutralising antibody (bNAb) therapy (3BNC117 and 10-1074).

Antiretroviral therapy was stopped and the antibodies infused at days 0, 21 and 42. She maintained an undetectable viral load for 20 weeks before viral rebound occurred.

Sequencing of the rebound virus demonstrated mutations conferring resistance to 10-1074, and serum antibody concentrations at rebound were <10 µg/mL.

Which of the following best explains the mechanism of viral rebound in this patient?

A 30-year-old man has been virologically suppressed on antiretroviral therapy for 5 years with a viral load persistently <20 copies/mL and a CD4 count of 780 cells/µL (reference range 500–1500 cells/µL).

He asks his physician whether stopping treatment now that he is “undetectable” would result in cure.

Which of the following best explains why cessation of antiretroviral therapy would result in viral rebound in this patient?

A 55-year-old man with HIV has been virologically suppressed on antiretroviral therapy for 10 years with an undetectable viral load and CD4 count of 640 cells/µL (reference range 500–1500 cells/µL).

He presents with an acute anterior myocardial infarction. He is a non-smoker with well-controlled blood pressure. Blood tests show elevated high-sensitivity C-reactive protein and elevated soluble CD14 and IL-6.

Which of the following pathophysiological processes best explains this patient’s increased cardiovascular risk despite virological suppression?

A 40-year-old man is newly diagnosed with HIV and is treatment-naive. His baseline investigations show:

• HIV RNA viral load: 90,000 copies/mL
• CD4 count: 350 cells/µL (reference range 500–1500 cells/µL)
• HLA-B*57:01: negative
• CMV IgG: positive
• He has a history of major depression and methamphetamine use

He asks about the likely course of his disease if factors were left unmodified.

Which of the following single interventions would most improve this patient’s long-term prognosis?

A 29-year-old man newly diagnosed with HIV is commenced on a fixed-dose combination of bictegravir, tenofovir alafenamide and emtricitabine. His baseline investigations show:

• HIV RNA viral load: 120,000 copies/mL
• CD4 count: 410 cells/µL (reference range 500–1500 cells/µL)
• HLA-B*57:01: negative
• HBsAg: negative

After 4 weeks of therapy his viral load has fallen particularly rapidly to 800 copies/mL.

Which step of the HIV lifecycle is inhibited by the drug component most likely responsible for this especially rapid decline in viral load?

A 47-year-old asymptomatic woman is newly diagnosed with HIV during antenatal-style screening. She feels well. Investigations show:

• HIV RNA viral load: 45,000 copies/mL
• CD4 count: 620 cells/µL (reference range 500–1500 cells/µL)
• HLA-B*57:01: negative
• HBsAg: negative

She asks whether she should wait until her CD4 count falls before starting treatment.

Which of the following is the most appropriate recommendation regarding initiation of antiretroviral therapy?

A 34-year-old man with HIV has been on bictegravir/tenofovir alafenamide/emtricitabine for 18 months. His viral load was undetectable for the first year. Recent results show:

• HIV RNA viral load: 8,000 copies/mL (previously <20 copies/mL)
• CD4 count: 510 cells/µL (reference range 500–1500 cells/µL)

On questioning, he admits to frequently missing doses over the past 3 months due to a change in work circumstances.

Which of the following is the most appropriate next step in management?

A 41-year-old man newly diagnosed with HIV is being planned for antiretroviral therapy. The treating team is considering an abacavir-containing regimen (dolutegravir/abacavir/lamivudine). His investigations show:

• HIV RNA viral load: 60,000 copies/mL
• CD4 count: 300 cells/µL (reference range 500–1500 cells/µL)
• HBsAg: negative

Which of the following investigations is essential before commencing this regimen to prevent a potentially fatal complication?

A 38-year-old woman with HIV/hepatitis B co-infection has been stable on tenofovir disoproxil fumarate/emtricitabine plus dolutegravir for 3 years. Her investigations show:

• HIV RNA viral load: <20 copies/mL
• HBsAg: positive
• HBV DNA: undetectable
• CD4 count: 650 cells/µL (reference range 500–1500 cells/µL)
• eGFR: falling, now 42 mL/min/1.73m² (previously >90)

The renal team recommends discontinuing tenofovir disoproxil fumarate due to nephrotoxicity.

Which of the following is the most important consideration when modifying her regimen?

A 33-year-old man with HIV has been virologically suppressed on a standard three-drug oral regimen for 2 years. He reports difficulty with daily tablet adherence due to a demanding travel schedule and requests a less burdensome option.

His investigations show:

• HIV RNA viral load: <20 copies/mL
• CD4 count: 720 cells/µL (reference range 500–1500 cells/µL)
• No documented resistance mutations
• HBsAg: negative

Which of the following options has the best supporting trial evidence as a switch strategy in a virologically suppressed patient seeking a reduced dosing burden?

A 36-year-old man with HIV has been on antiretroviral therapy for 18 months with a viral load consistently <20 copies/mL and a CD4 count of 690 cells/µL (reference range 500–1500 cells/µL).

He is in a stable serodifferent relationship (his partner is HIV negative) and asks about the risk of transmitting HIV to his partner through condomless sex now that his viral load is undetectable.

Which of the following is the most accurate advice regarding the risk of sexual transmission in this scenario?

A 27-year-old male healthcare worker sustains a deep percutaneous needlestick injury while taking blood from a patient known to be HIV positive with a detectable viral load. He presents 2 hours after the injury. His baseline investigations show:

• HIV serology: negative
• HIV RNA viral load: undetectable
• Hepatitis B surface antibody: >100 mIU/mL (immune)
• Creatinine, LFTs and FBC: within normal limits

He is commenced on three-drug post-exposure prophylaxis.

Which of the following best explains the pathophysiological rationale for commencing prophylaxis as soon as possible after this exposure?

A 24-year-old man presents 36 hours after receptive anal intercourse with ejaculation with a casual male partner who has subsequently disclosed that he is HIV positive.

The partner states he is on antiretroviral therapy but is uncertain about his most recent viral load result and has missed several doses recently. The exposed man’s baseline investigations show:

• HIV serology: negative
• HIV RNA viral load: undetectable
• Creatinine, LFTs, FBC: within normal limits
• Pregnancy test: not applicable

Which of the following is the most appropriate management?

A 31-year-old man requests pre-exposure prophylaxis after several recent episodes of condomless receptive anal intercourse with casual partners.

He mentions that 10 days ago he developed fever, sore throat, myalgia, a maculopapular rash and generalised lymphadenopathy, which are now resolving. His investigations show:

• HIV Ag/Ab combination immunoassay: negative
• Creatinine and eGFR: normal
• Hepatitis B, C and syphilis serology: negative

Which of the following is the most appropriate next step before prescribing PrEP?

A 29-year-old cis-gender man who has sex with men requests PrEP. His HIV risk arises solely from episodic condomless anal intercourse with casual male partners, which he can usually anticipate. He does not inject drugs. His investigations show:

• HIV Ag/Ab immunoassay: negative
• HIV RNA: not detected
• eGFR: 95 mL/min/1.73m² (reference range >90)
• HBsAg: negative; anti-HBs: positive (immune)
• Syphilis, chlamydia and gonorrhoea screening: negative

He prefers not to take a daily tablet and asks whether an event-based regimen is suitable for him.

Which of the following is the most appropriate PrEP regimen for this patient?

A 35-year-old man is being assessed for daily PrEP. His baseline investigations show:

• HIV Ag/Ab immunoassay: negative; HIV RNA: not detected
• eGFR: 88 mL/min/1.73m² (reference range >90)
• HBsAg: positive
• anti-HBc: positive; HBV DNA: 4,500 IU/mL
• ALT: 62 U/L (reference range <40 U/L)

Which of the following is the most important consideration in this patient’s management?

A 26-year-old man who has been prescribed daily tenofovir/emtricitabine PrEP for 6 months presents for review. He reports that he frequently forgets doses and estimates he takes “one or two tablets a week.”

He continues to have condomless receptive anal intercourse with multiple casual partners. His investigations show:

• HIV Ag/Ab immunoassay: negative; HIV RNA: not detected
• eGFR: 90 mL/min/1.73m² (reference range >90)
• Rectal chlamydia: positive

Which of the following best explains the principal concern regarding this patient’s HIV risk?

A 40-year-old man attends with his HIV-negative male partner. He has been living with HIV and on antiretroviral therapy for 3 years. His investigations show:

• HIV RNA viral load: <20 copies/mL on the most recent three consecutive tests over 12 months
• CD4 count: 680 cells/µL (reference range 500–1500 cells/µL)

The couple wish to stop using condoms and ask whether the HIV-negative partner needs to start PrEP to remain protected.

Which of the following is the most accurate advice?

A 30-year-old woman at ongoing high risk of HIV through condomless heterosexual intercourse has struggled with daily oral PrEP adherence despite repeated counselling. She asks about alternative preventive options.

Her investigations show:

• HIV Ag/Ab immunoassay: negative; HIV RNA: not detected
• eGFR: 92 mL/min/1.73m² (reference range >90)
• HBsAg: negative; anti-HBs: positive
• Pregnancy test: negative

Which of the following long-acting prevention strategies has the strongest randomised trial evidence of superiority to daily oral tenofovir/emtricitabine in women?

A 34-year-old man is diagnosed with HIV after presenting with several weeks of progressive exertional dyspnoea, dry cough, fever and 15% weight loss.

On examination he has oral thrush and his chest auscultation is unremarkable. His investigations show:

• SpO₂ 93% on room air at rest, falling to 85% on ambulation
• CD4 count: 85 cells/µL (reference range 500–1500 cells/µL)
• Chest radiograph: bilateral diffuse perihilar interstitial infiltrates
• Serum lactate dehydrogenase (LDH): markedly elevated
• Arterial blood gas (room air): PaO₂ 68 mmHg

Which of the following investigations is most likely to confirm the underlying diagnosis?

A 36-year-old man with newly diagnosed HIV (CD4 count 60 cells/µL, reference range 500–1500 cells/µL) is confirmed to have Pneumocystis jirovecii pneumonia on bronchoalveolar lavage.

His arterial blood gas on room air shows:

• PaO₂ 68 mmHg
• Alveolar–arterial (A–a) oxygen gradient: 42 mmHg
• SpO₂ 90% on room air

He is commenced on trimethoprim-sulfamethoxazole.

In addition to antimicrobial therapy, which of the following interventions will most reduce his risk of mortality?

A 40-year-old man has completed 21 days of treatment for a first episode of Pneumocystis jirovecii pneumonia. He has commenced antiretroviral therapy.

His investigations show:

• CD4 count: 72 cells/µL (reference range 500–1500 cells/µL)
• HIV RNA viral load: 180,000 copies/mL (pre-treatment)
• G6PD level: normal

Which of the following is the most appropriate ongoing management to prevent recurrence?

A 38-year-old man with HIV who is not on antiretroviral therapy presents with a 2-week history of fever, malaise and progressively worsening headache.

On examination he is lethargic but there is no neck stiffness or photophobia. His investigations show:

• CD4 count (6 months ago): 150 cells/µL (reference range 500–1500 cells/µL)
• CT brain: no mass lesion, no hydrocephalus
• Lumbar puncture: opening pressure 32 cmH₂O (reference range 10–20 cmH₂O)
• CSF white cell count: mildly elevated with lymphocyte predominance
• CSF protein: mildly elevated; CSF glucose: low
• CSF India ink: positive for encapsulated yeasts

Which of the following CSF investigations is most sensitive and specific for confirming the diagnosis?

A 35-year-old woman with advanced HIV is diagnosed with cryptococcal meningitis (CSF CrAg positive, opening pressure 30 cmH₂O [reference range 10–20 cmH₂O]).

Her CD4 count is 40 cells/µL (reference range 500–1500 cells/µL). She is not yet on antiretroviral therapy.

Which of the following induction regimens has the strongest evidence of superior efficacy for this infection?

A 25-year-old woman recently arrived from Thailand presents with 2 weeks of headache, fever and diplopia. On examination she has a partial sixth nerve palsy.

Her investigations show:

• HIV serology: positive (new diagnosis)
• CD4 count: 45 cells/µL (reference range 500–1500 cells/µL)
• MRI brain: a solitary ring-enhancing lesion in the right midbrain with surrounding oedema
• Serum Toxoplasma IgG: positive

Which of the following is the most appropriate initial management?

A 33-year-old man with newly diagnosed HIV is being treated for Pneumocystis jirovecii pneumonia and is improving.

His investigations show:

• CD4 count: 55 cells/µL (reference range 500–1500 cells/µL)
• HIV RNA viral load: 250,000 copies/mL

He is antiretroviral-naive. The team is deciding when to start antiretroviral therapy.

Which of the following is the most appropriate timing for initiation of antiretroviral therapy?

A 32-year-old man with advanced HIV (baseline CD4 count 30 cells/µL, reference range 500–1500 cells/µL) was diagnosed and treated for cryptococcal meningitis. Antiretroviral therapy was commenced 6 weeks later.

Two weeks after starting antiretroviral therapy he re-presents with worsening headache, fever and a reduced level of consciousness. His investigations show:

• CD4 count: now 140 cells/µL (rising)
• HIV RNA viral load: fallen from 400,000 to 3,000 copies/mL
• Repeat lumbar puncture: raised opening pressure 34 cmH₂O (reference range 10–20 cmH₂O), elevated white cell count
• CSF fungal culture: no growth (sterile)

Which of the following best explains this patient’s deterioration?