A 58-year-old woman with HIV infection is brought to the emergency department because of a 2-week history of headaches, blurred vision, and confusion. Her current medications include antiretroviral therapy and trimethoprim-sulfamethoxazole. Neurological examination shows ataxia and memory impairment. Her CD4+ T-lymphocyte count is 90/μL. Cerebrospinal fluid analysis shows lymphocytic predominant pleocytosis, and PCR is positive for Epstein-Barr virus DNA. An MRI of the brain with contrast shows a solitary, weakly ring-enhancing lesion with well-defined borders involving the corpus callosum. Which of the following is the most likely diagnosis?

Progressive multifocal leukoencephalopathy

A 52-year-old man is brought to the emergency department because of headaches, vertigo, and changes to his personality for the past few weeks. He was diagnosed with HIV 14 years ago and was started on antiretroviral therapy at that time. Medical records from one month ago indicate that he followed his medication schedule inconsistently. Since then, he has been regularly taking his antiretroviral medications and trimethoprim-sulfamethoxazole. His vital signs are within normal limits. Neurological examination shows ataxia and apathy. Mini-Mental State Examination score is 15/30. Laboratory studies show: Hemoglobin 12.5 g/dL Leukocyte count 8400/mm3 Segmented neutrophils 80% Eosinophils 1% Lymphocytes 17% Monocytes 2% CD4+ T-lymphocytes 90/μL Platelet count 328,000/mm3 An MRI of the brain with contrast shows a solitary ring-enhancing lesion involving the corpus callosum and measuring 4.5 cm in diameter. A lumbar puncture with subsequent cerebrospinal fluid analysis shows slight pleocytosis, and PCR is positive for Epstein-Barr virus DNA. Which of the following is the most likely diagnosis?

Progressive multifocal leukoencephalopathy

A 44-year-old man with HIV comes to the physician for a routine follow-up examination. He has been noncompliant with his antiretroviral medication regimen for several years. He appears chronically ill and fatigued. CD4+ T-lymphocyte count is 180/mm³ (N ≥ 500). Further evaluation of this patient is most likely to show which of the following findings?

Violaceous lesions on skin exam

Multifocal demyelination on brain MRI

Ring-enhancing lesions on brain MRI

Cotton-wool spots on fundoscopy

Ground-glass opacities on chest CT

A 52-year-old woman presents to a local hospital complaining about a rash on her face and torso, as well as night sweats, low-grade fever, diarrhea, and unintentional weight loss. Her personal history is relevant for homelessness; she also has a history of risky behaviors such as the use and abuse of intravenous drugs, and unprotected intercourse with multiple sexual partners. Upon physical examination, well-demarcated violaceous plaques and papules distributed on her face and back are visible (see image below). Additional findings include fine reticular and interstitial changes on a chest radiograph, a CD4+ count of 50 cells/mm3, and positive HIV serology. Which of the following is the most likely etiology of this patient's dermatological condition?

Human alphaherpesvirus 3 (HHV-3) infection

HIV-associated malignancies for USMLE Step 1: High-Yield Microbiology Lessons

HIV & Malignancy - The Unholy Alliance

Mechanism: A triad of immunosuppression (low CD4 count), chronic inflammation, and co-infection with oncogenic viruses drives malignancy risk.
Key Viral Co-infections:
- HHV-8: Kaposi Sarcoma
- EBV: Primary CNS Lymphoma, Burkitt Lymphoma
- HPV: Cervical & Anal Cancer
HAART Era Shift: While effective antiretroviral therapy has ↓ AIDS-defining cancers (ADCs), non-AIDS-defining cancers (NADCs) like lung and liver cancer are now more common due to longer lifespans.

⭐ Primary CNS Lymphoma in an HIV patient is almost always associated with EBV infection and typically occurs with CD4 counts < 50/mm³.

Kaposi sarcoma lesions on skin of HIV patient

AIDS-Defining Cancers - The Classic Trio

The risk of certain cancers skyrockets with severe immunosuppression (CD4+ < 200 cells/μL). These virally-driven malignancies are hallmarks of advanced HIV disease and are recognized as AIDS-defining conditions.

Kaposi sarcoma lesions on abdomen of AIDS patient

Malignancy	Associated Virus	Key Presentation	Diagnostic Clue
Kaposi Sarcoma	HHV-8	Violaceous papules/nodules on skin, hard palate, GI tract, or respiratory tract.	Biopsy: Spindle cells, neovascularization, and extravasated RBCs.
Primary CNS Lymphoma	EBV	Altered mental status, seizures, or focal neurological deficits. Typically a single ring-enhancing lesion on contrast MRI.	Definitive diagnosis via brain biopsy. EBV DNA in CSF is highly suggestive.
Invasive Cervical Cancer	HPV (16, 18)	Abnormal vaginal bleeding (often post-coital), pelvic pain, or vaginal discharge. HIV+ women require more frequent screening.	Pap smear shows dysplasia (CIN); confirmed by colposcopy and biopsy.

Emerging Threats - The NADC List

With effective antiretroviral therapy (ART), patients with HIV live longer but face a rising tide of Non-AIDS-Defining Cancers (NADCs). These are now a more frequent cause of mortality than classic AIDS-defining cancers in the ART era.

Key NADCs & Viral Associations:
- Anal Cancer: Human Papillomavirus (HPV)
- Hodgkin Lymphoma: Epstein-Barr Virus (EBV)
- Hepatocellular Carcinoma: Hepatitis B (HBV) & C (HCV)
- Lung Cancer: ↑ risk independent of smoking.

⭐ In the HIV population, the standardized incidence ratio for anal cancer and Hodgkin lymphoma is significantly elevated compared to the general population.

Mechanism of Malice - How HIV Drives Cancer

HIV cripples the immune system, creating a permissive environment for cancer through two primary mechanisms:

⭐ Most HIV-associated lymphomas are aggressive, high-grade B-cell types (e.g., Diffuse Large B-cell, Burkitt). Primary CNS lymphoma, caused by EBV, is an AIDS-defining illness and often presents with a solitary ring-enhancing lesion on imaging.

High‑Yield Points - ⚡ Biggest Takeaways

Kaposi Sarcoma, caused by HHV-8, presents with characteristic violaceous skin lesions.

Primary CNS Lymphoma, driven by EBV, typically appears as a solitary, ring-enhancing lesion on brain MRI.

Systemic Non-Hodgkin Lymphomas are also EBV-related and frequently present in extranodal sites.

Invasive cervical and anal cancers, caused by HPV, have a significantly higher incidence and more rapid progression.

These malignancies often serve as an AIDS-defining illness.

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