What is the most likely diagnosis in a 27‑year‑old bisexual man with HIV on Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide) and low viral load, presenting with 20 days of nausea, vomiting, fever, and abdominal pain after recent amoxicillin and prednisone for streptococcal infection?

Differential Diagnosis: CMV Colitis or Typhlitis in HIV Patient on Biktarvy

The most likely diagnosis in this 27-year-old man with HIV on Biktarvy presenting with 20 days of nausea, vomiting, fever, and abdominal pain after recent steroid exposure is CMV colitis or neutropenic enterocolitis (typhlitis), both of which require urgent contrast-enhanced CT imaging and hospital admission for close monitoring and potential surgical consultation.

Critical Clinical Context

This patient's presentation raises several red flags that demand immediate attention:

• Prolonged symptoms (20 days) with fever, nausea, vomiting, and abdominal pain despite recent antibiotic treatment 1
• Recent prednisone exposure increases risk of opportunistic infections and surgical complications 1
• HIV status requires consideration of HIV-specific surgical diseases including CMV colitis, Mycobacterium avium complex, and abdominal tuberculosis 1
• Immunocompromised state means clinical signs may be unreliable—the more severe the immunocompromise, the less reliable the physical findings 1

Immediate Diagnostic Workup Required

Laboratory Evaluation

• Complete blood count to assess for neutropenia, anemia, or hematologic abnormalities 1, 2
• Comprehensive metabolic panel including liver enzymes, as significantly elevated AST (>273 U/L) or ALT (>108 U/L) with GI symptoms requires inpatient monitoring 2, 3
• AST:ALT ratio of approximately 3:1 signals severe liver injury necessitating serial monitoring 2, 3
• Serum lactate when bowel ischemia is suspected (severe pain, peritoneal signs, hemodynamic instability) 2
• C-reactive protein is fundamental in differential diagnosis of immunocompromised patients 1
• Stool testing for Clostridioides difficile and its toxin, as diarrhea with or without acute abdomen mandates this test 1

Imaging Strategy

Contrast-enhanced CT of the abdomen and pelvis is mandatory as the first-line modality for acute abdominal pain in immunocompromised patients 1, 2. Plain radiographs and ultrasound are insufficiently sensitive and specific in this population 1. CT reliably identifies:

• Small-bowel obstruction, its cause, location, and complications such as ischemia 2
• Neutropenic enterocolitis (typhlitis) with bowel wall thickening, particularly in the cecum 1
• Mesenteric ischemia, perforation, or abscess formation 1, 2

Primary Differential Diagnoses

1. CMV Colitis (Most Likely)

• HIV-associated opportunistic infection that presents with prolonged GI symptoms, fever, and abdominal pain 1
• Steroid exposure significantly increases CMV reactivation risk 1
• Despite low viral load on Biktarvy, CMV colitis can occur, particularly with recent immunosuppression from prednisone 1
• Requires colonoscopy with biopsy for definitive diagnosis showing CMV inclusion bodies 1

2. Neutropenic Enterocolitis (Typhlitis)

• High mortality if misdiagnosed or underestimated; accurate differential diagnosis is mandatory 1
• Presents with fever, abdominal pain (particularly right lower quadrant), nausea, and vomiting 1
• Treatment should be nonoperative including broad-spectrum antibiotics and bowel rest; emergency surgery reserved only for perforation or ischemia 1
• Damage control approach should be adopted in severely sick patients with physiological derangement 1

3. Clostridioides difficile Colitis

• Must be tested in any immunocompromised patient with diarrhea and abdominal pain 1
• Recent amoxicillin exposure is a significant risk factor 1
• Specific testing for C. difficile toxin should be performed 1

4. Drug-Induced Hepatotoxicity

• Biktarvy (B/F/TAF) can cause nausea (reported in 2-13% of patients in clinical trials) 4, 5
• However, nausea as a drug-related adverse event typically occurs early in treatment, not after one year of therapy 6
• Amoxicillin and prednisone can both cause hepatotoxicity 1
• Elevated liver enzymes with GI symptoms require inpatient monitoring 2, 3

Hospital Admission Criteria Met

This patient meets multiple criteria for immediate hospital admission:

• Prolonged symptoms (20 days) unresponsive to outpatient treatment 1
• Immunocompromised status with HIV requiring close monitoring 1
• Recent steroid exposure with higher risk of surgical complications 1
• Potential for markedly elevated liver enzymes requiring serial monitoring 2, 3
• Risk of bowel ischemia, perforation, or neutropenic enterocolitis mandating surgical consultation availability 1, 2

Inpatient Management Priorities

• Serial liver function tests to detect worsening hepatic injury 2, 3
• Continuous vital-sign monitoring and repeat laboratory assessments to track enzyme trends 3
• Prompt surgical consultation for any peritoneal signs or imaging evidence of ischemia, perforation, or obstruction 1, 2
• Broad-spectrum antibiotics if neutropenic enterocolitis or bacterial infection suspected 1
• Maintain usual steroid regimen if patient was on chronic steroids; consider stress-dose hydrocortisone 100 mg IV if unexplained hypotension occurs 1

Critical Pitfalls to Avoid

• Do not dismiss prolonged symptoms in immunocompromised patients as simple gastroenteritis 1
• Do not rely on physical examination alone—fever, leukocytosis, and peritoneal signs may be mild or absent in severe immunocompromise 1
• Do not delay CT imaging in favor of plain radiographs or ultrasound, which are insufficiently sensitive 1, 2
• Do not assume Biktarvy is well-tolerated without considering drug-induced hepatotoxicity, though this is less likely after one year of therapy 6
• Do not miss C. difficile testing given recent antibiotic exposure 1
• Pain out of proportion to examination findings is classic for early mesenteric ischemia and must not be dismissed 2

Nuances in This Case

The combination of well-controlled HIV (low viral load on Biktarvy) with recent prednisone exposure creates a unique risk profile. While Biktarvy maintains excellent virologic suppression (>94% at one year) 5, 6, the recent steroid course temporarily increases opportunistic infection risk despite good HIV control. The 20-day duration of symptoms is particularly concerning and argues against simple viral gastroenteritis or drug-related nausea from Biktarvy, which would typically resolve or occur early in treatment 4, 6.

Immediate hospital admission with contrast-enhanced CT imaging, comprehensive laboratory evaluation including liver enzymes and C. difficile testing, and readiness for surgical consultation is the appropriate management strategy 1, 2, 3.