HIV

HIV Clinical Medicine MCQs: Cases and Explanations

• Acute HIV Infection Case     * Patient Profile: A 24-year-old man presenting with fever, sore throat, diffuse rash, and lymphadenopathy.     * Timeline: Symptoms appeared 3 weeks after unprotected sexual intercourse.     * Initial Test: Rapid HIV antibody test is negative.     * Management: The best next step is to order quantitative HIV RNA testing.     * Clinical Reasoning: Acute HIV infection (AHI) often occurs before antibodies develop. During this phase, the viral load is extremely high, making HIV RNA (Nucleic Acid Test/NAT) the most sensitive diagnostic tool. A negative antibody test does not rule out acute infection. Symptoms often mimic influenza, but exposure history must guide clinical suspicion.

• AIDS Diagnostic Criteria Case     * Thresholds: AIDS is diagnosed when a patient has a CD4 count < 200\,cells/mm^3 OR the presence of an AIDS-defining illness.     * Examples:         * CD4 count $180\,cells/mm^3$ without symptoms fulfills criteria.         * Oral candidiasis is suggestive of immune dysfunction but is not automatically an AIDS-defining illness in the absence of esophageal involvement.         * Viral load (e.g., $50\,copies/mL$) or a positive antibody test alone does not define AIDS without satisfying the CD4 or opportunistic infection criteria.

• Pneumocystis jirovecii Pneumonia (PJP) Case     * Patient Profile: 39-year-old HIV-positive patient.     * Symptoms: Progressive dyspnea, fever, dry cough, and severe hypoxemia.     * Imaging: Chest X-ray (CXR) shows diffuse bilateral perihilar infiltrates.     * Differential Diagnosis:         * PJP: Classic presentation of opportunistic infection with diffuse infiltrates and dry cough.         * Bacterial Pneumonia: Typically presents with focal consolidation.         * Tuberculosis (TB): Usually presents with more chronic symptoms and upper lobe cavitary lesions.         * Pulmonary Embolism (PE): Does not cause diffuse bilateral perihilar infiltrates.

• Opportunistic Infection (OI) Prophylaxis Case     * PJP Prophylaxis: Indicated when CD4 count is < 200\,cells/mm^3. First-line therapy is Trimethoprim-sulfamethoxazole (TMP-SMX).     * MAC Prophylaxis: Use Azithromycin for Mycobacterium Avium Complex (MAC) when CD4 count is < 50\,cells/mm^3.     * Fluconazole: Not used for routine prophylaxis.     * Rifampin: Used for TB treatment, not general HIV prophylaxis in this context.

• CNS Lesions in HIV Case     * Symptoms: Seizures and focal neurologic deficits.     * Imaging: CT shows multiple ring-enhancing lesions.     * Likely Diagnosis: Toxoplasmosis (the most common CNS lesion in HIV).     * Comparison:         * Primary CNS Lymphoma: Usually presents as a solitary (single) lesion.         * Stroke: Does not cause ring-enhancing lesions.         * Progressive Multifocal Leukoencephalopathy (PML): Characterized by non-enhancing white matter lesions.

• HIV Medication Toxicity and Screening Cases     * Tenofovir Disoproxil Fumarate (TDF): Associated with nephrotoxicity (renal dysfunction) and decreased bone mineral density.     * Abacavir (ABC): Associated with a hypersensitivity reaction. Mandatory testing for the $HLA-B<em>5701$ allele is required prior to initiation.      Dolutegravir (DTG): Associated with weight gain.     * Atazanavir (ATV): Known for causing hyperbilirubinemia (jaundice).

• HIV Prevention and Monitoring Cases     * Viral Load Goal: Effective Antiretroviral Therapy (ART) aims for suppression below $200\,copies/mL$, ideally to undetectable levels.     * U=U (Undetectable = Untransmittable): Means that an undetectable viral load prevents the sexual transmission of HIV. It does not cure HIV or prevent the transmission of other Sexually Transmitted Infections (STIs).     * PrEP Selection: F/TDF (Truvada) is the only oral option approved for vaginal sex, anal sex, and injection drug use. F/TAF (Descovy) is not approved for receptive vaginal sex.     * PrEP and Acute Infection: If a patient has symptoms concerning for acute HIV, quantitative HIV RNA testing must be obtained before starting PrEP to avoid developing drug resistance through partial treatment.     * PEP Timing: Post-Exposure Prophylaxis (PEP) must be started within $72\,hours$ of a potential exposure (e.g., needle-stick injury).

History and Epidemiology of HIV/AIDS

• Historical Timeline     * 1981: Increased reports of Pneumocystis and Kaposi Sarcoma in otherwise healthy young men; initially classified as GRID (Gay Related Immune Disease).     * 1982: Named AIDS by the CDC; discovered to be transmissible through blood/perinatal transfusions.     * 1983: Casual contact confirmed NOT to be a risk factor.     * 1984: Needle sharing identified as a risk factor; HIV is identified.     * 1987: First antiretroviral (AZT) introduced.     * 1996: Combination ART (cART) revolutionized treatment.

• Social and Behavioral Context     * Stigma: Refers to attitudes and beliefs labeling people with HIV as socially unacceptable.     * Discrimination: Behaviors and differential treatment resulting from stigma.     * Inclusive History Taking: Normalize the process, use non-judgmental language, avoid assumptions, and focus on anatomy/practices ("what goes where") rather than orientation.

• Demographics and Regional Distribution     * Gender: Men account for $79\%$ of cases. Breakdown: Male-to-male ($67\%$), Heterosexual contact ($22\%$), IVDU ($7\%$), Perinatal (< 1\%).     * Ethnicity: Black/African American ($38\%$), Hispanic/Latino ($32\%$), White ($24\%$), Asian ($2\%$).     * Age: Ages 13-34 account for the majority of new infections ($56\%$ total; 25-34 being $37\%$).     * Region: The South accounts for the highest burden in the US at $52\%$, followed by the West ($21\%$), Midwest ($13\%$), and Northeast ($13\%$).

HIV Pathophysiology and Clinical Stages

• Viral Mechanism     * HIV is a retrovirus that integrates permanently into the host genome.     * Targets: CD4 cells (T-lymphocytes).     * Cell Cycle: The virion uses CD4 cells to replicate; this replication process destroys the cell, leading to immune system dysfunction.     * Consequences of Decreased Immunity: Increased susceptibility to infections, neoplasms, autoimmune (AI) conditions, and allergic/hypersensitivity (HS) reactions.

• Transmission Routes     * Bodily Fluids: Blood, semen, vaginal secretions, breast milk, and Cerebrospinal Fluid (CSF).     * High-Risk Behaviors: Injection drug use (IVDU), sexual intercourse, vertical transmission (in utero, childbirth, breastfeeding), blood transfusions, and occupational exposure.     * Risk Factors: Inconsistent condom use, unknown partner status, drug/alcohol use during sex (e.g., "poppers"/amyl nitrite), and transactional sex.

• Clinical Stages of Infection     * Acute HIV Infection: 2–4 weeks after exposure. Characterized by flu-like/mono-like symptoms, extremely high viral load, and establishment of a viral reservoir. Requires Ag/Ab or RNA testing.     * Clinical Latency: Asymptomatic/chronic phase. Virus reproduces at low levels; can last a decade or longer. CD4 count slowly declines.     * AIDS: Severe damage to the immune system. Defined by CD4 < 200\,cells/mm^3 or the presence of AIDS-defining conditions.

Systemic Manifestations and Opportunistic Infections

• Pulmonary and Gastrointestinal Findings     * Wasting Syndrome: Significant weight loss and loss of muscle mass, often accompanied by N/V, anorexia, and malabsorption.     * Pneumonia: Defined as occurring > 1/year. Includes bacterial, mycobacterial (TB), and fungal (PJP) causes.     * Tuberculosis: Higher risk in homeless populations; requires resistance testing due to Multi-Drug Resistant (MDR) TB risk.

• Integumentary and Oral Manifestations     * Viral Skin Infections: Disseminated Herpes Zoster, severe/disseminated HSV, and widespread Molluscum Contagiosum (facial/neck distribution suggests severe immunosuppression).     * Bacterial/Fungal Skin Infections: Staph, furuncles, bullous impetigo, and seborrheic dermatitis.     * Oral Signs: Oral Candidiasis (white plaques) and Hairy Leukoplakia (EBV-related, lateral tongue). These are suggestive of HIV in otherwise healthy individuals.     * Gingival Disease: Periodontitis and severe gingival overgrowth.

• Neurologic and CNS Disease     * HIV-Associated Dementia: Issues with memory, attention, cognition, and motor/fine-motor function (e.g., writing). It is a diagnosis of exclusion.     * Toxoplasmosis: Most common CNS lesion; typically presents in seropositive patients with multiple contrast-enhancing lesions on imaging.     * CNS Lymphoma: Second most common CNS lesion; associated with EBV. Often appears as a solitary lesion and requires brain biopsy for definitive diagnosis.     * Meningitis: Can be cryptococcal (elevated ICP), meningococcal, or HIV-related.

Opportunistic Infection (OI) Prophylaxis Summary

• General Principles: Initiation is based on CD4 counts. Prophylaxis can be discontinued if CD4 counts increase sustainably due to ART.

• Target CD4 Thresholds:     * CD4 < 200\,cells/mm^3 (PJP): TMP-SMX (1 Double Strength tablet daily). Alternative: Dapsone (if allergic).     * CD4 < 100\,cells/mm^3 (Toxoplasmosis): TMP-SMX. Alternative: Dapsone + Pyrimethamine + Leucovorin.     * CD4 < 50\,cells/mm^3 (MAC): Azithromycin ($1200\,mg$ PO weekly). Alternative: Clarithromycin ($500\,mg$ PO BID).

Management and Antiretroviral Therapy (ART)

• Entry into Care: Initial Evaluation     * Comprehensive History: STI screening (mouth, vagina, rectum), treatment history, and mental health evaluation.     * Baseline Labs: HIV Serology (confirm status), Viral Load (Quant HIV RNA), CD4 Count, Genotypic Resistance testing, $HLA-B*5701$ (if considering ABC), Tropism testing (if considering CCR5 antagonists), Hepatitis B/C serology, CBC, CMP, Lipids, UA, and Pregnancy test.

• ART Medication Classes     1. NRTIs (Nucleoside Reverse Transcriptase Inhibitors): Tenofovir (TDF/TAF), Emtricitabine (FTC), Abacavir (ABC), Lamivudine (3TC).     2. NNRTIs (Non-nucleoside): Doravirine (DOR), Rilpivirine (RPV).     3. INSTIs (Integrase Transfer Strand Inhibitors): Bictegravir (BIC), Dolutegravir (DTG), Raltegravir (RAL).     4. PIs (Protease Inhibitors): Darunavir (DRV), Atazanavir (ATV).     5. PK Enhancers/Boosters: Ritonavir (/r), Cobicistat (/c).     6. Others: Fusion inhibitors, CCR5 antagonists, Post-attachment inhibitors, Attachment inhibitors, Capsid inhibitors (Lenacapavir).

• Standard Treatment Regimen     * Backbone: 2 NRTIs.     * Additional Agent: 1 INSTI, NNRTI, or Boosted PI.     * Target: Viral load < 200\,copies/mL (ideally Undetectable).

• Specific Initial Regimens     * No Prior CAB (PrEP) Exposure: BIC/TAF/FTC OR DTG + (TAF/TDF) + (FTC/3TC) OR DTG/3TC (Only if HIV RNA < 500,000\,copies/mL, no HBV, and genotype results known).     * Previous CAB Exposure: Requires INSTI genotype testing; often utilize DRV/c or DRV/r + (TAF/TDF) + (FTC/3TC).     * Renal/Bone Concerns: Prefer TAF over TDF; consider DTG/ABC/3TC (if $HLA-B*5701$ negative).

Pre-Exposure Prophylaxis (PrEP) and Post-Exposure Prophylaxis (PEP)

• PrEP Options     * F/TDF (Truvada): Oral daily for vaginal sex, anal sex, and IVDU. Associated with $10\%$ renal/bone density decline.     * F/TAF (Descovy): Oral daily for anal sex only (male/female). Lower renal/bone toxicity but can increase LDL.     * Cabotegravir (CAB/Apretude): Long-acting IM injection every 2 months (after initial 4-week dose). Monitor for depressive disorders and injection site reactions.     * Lenacapavir (LEN/Yeztugo): Capsid inhibitor; SC injection every 6 months (26 weeks).

• 2-1-1 PrEP (On-Demand)     * Not FDA approved but studied with F/TDF.     * Dosing: 2 pills $2-24\,hours$ before sex, then 1 pill $24\,hours$ after sex, then 1 pill $48\,hours$ after the first dose.

• Ongoing PrEP Management     * Follow-up: Oral PrEP every 3 months; injectable every 2 or 6 months.     * Testing at each visit: HIV Ab/Ag testing and HIV-Quant RNA.     * Renal Function: Required for oral options.     * HBV Awareness: FTC/TDF treats Hep B; discontinuing it may cause HBV rebound/flare.     * The CAB "Tail": After discontinuing CAB, subtherapeutic levels remain. To prevent resistance, high-risk patients should transition to oral PrEP and undergo quarterly HIV screening for 1 year.

• PEP (Post-Exposure Prophylaxis)     * Eligibility: Source HIV+ or unknown; exposure within $72\,hours$.     * Regimen (28 days): F/TDF + Raltegravir OR Dolutegravir OR (Darunavir + Ritonavir).