12.3 Bloodborne Infectious Disease Screening: HIV & Hepatitis C

ABFM Family Medicine Certification Study Guide Exam

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1 Chapter 1: Exam Structure, Blueprint & Clinical Decision-Making

1.1 Exam Blueprint, FMCLA vs. One-Day Exam & Board Scoring 1.2 Clinical Reasoning, Test-Taking Strategy & Ambiguity Management 1.3 Evidence-Based Medicine & Clinical Practice Guidelines in Primary Care

2 Chapter 2: Healthcare Systems, Practice Management & Quality

2.1 Practice Management, Billing, Coding & Documentation 2.2 Quality Improvement, Patient Safety & Diagnostic Stewardship 2.3 Interprofessional Team-Based Care & Care Coordination

3 Chapter 3: Ethics, Law, Biostatistics & Health Equity

3.1 Medical Ethics, Informed Consent & Surrogate Decision-Making 3.2 Biostatistics, Clinical Epidemiology & Diagnostic Test Interpretation 3.3 Social Determinants of Health, Health Equity & Cultural Humility 3.4 Physician Wellness, Burnout Prevention & Professionalism

4 Chapter 4: Lifestyle Counseling & Behavior Change

4.1 Alcohol Use Screening & Brief Intervention 4.2 Illicit Drug & Cannabis Counseling 4.3 Tobacco & Vaping Cessation Counseling

5 Chapter 5: Nutrition, Physical Activity & Chronic Disease Prevention

5.1 Dietary Counseling for Obesity & Chronic Disease Prevention 5.2 Exercise Prescription & Physical Activity Counseling 5.3 Genetic Risk Assessment & Family History Counseling

6 Chapter 6: Routine Adult Immunizations

6.1 ACIP Adult Respiratory Vaccines: Influenza, COVID-19, RSV & Pneumococcal 6.2 ACIP Adult Non-Respiratory Vaccines: Tdap, Shingrix, HPV & Hep B 6.3 Immunizations in Special Populations: Pregnancy, Asplenia & Immunocompromise

7 Chapter 7: Pediatric Health Maintenance & Surveillance

7.1 Newborn Examination & Early Postnatal Care 7.2 Well-Child Care, Developmental Surveillance & Milestones 7.3 Pediatric & Adolescent Screening: Vision, Hearing, Anemia & Lead 7.4 Pediatric Oral Health, Dental Screening & Fluoride

8 Chapter 8: Behavioral Health & Safety Screening

8.1 Primary Care Depression, Anxiety & Behavioral Health Screening 8.2 Domestic Violence, Intimate Partner Violence & Firearm Safety 8.3 Occupational Health & Recreational Safety Counseling

9 Chapter 9: Adult Preventive Screening: Cardiovascular & Metabolic

9.1 Cardiovascular Disease & Hypertension Screening 9.2 Type 2 Diabetes Screening & Prediabetes Risk Stratification 9.3 Abdominal Aortic Aneurysm & Osteoporosis Screening

10 Chapter 10: Adult Cancer Screening: Breast & Gynecologic

10.1 Breast Cancer Screening & Risk-Assessment 10.2 Cervical Cancer Screening & ASCCP Algorithms 10.3 Skin Cancer Clinical Assessment & Counseling

11 Chapter 11: Adult Cancer Screening: Colorectal, Lung & Prostate

11.1 Colorectal Cancer Screening Modalities & Intervals 11.2 Lung Cancer Screening with Low-Dose CT 11.3 Prostate Cancer Screening & Shared Decision-Making

12 Chapter 12: Sexual Health, Infectious Disease Screening & Contraception

12.1 Sexual Health Counseling & Risk-Reduction Strategies 12.2 STI Screening: Chlamydia, Gonorrhea, Syphilis & Trichomoniasis 12.3 Bloodborne Infectious Disease Screening: HIV & Hepatitis C

13 Chapter 13: Reproductive Life Planning, Lactation & Preoperative Care

13.1 Preconception Planning & Comprehensive Contraception Management 13.2 Lactation Support & Breastfeeding Counseling 13.3 Preoperative Medical Evaluation & Pre-Participation Sports Exam

14 Chapter 14: Emergent Cardiovascular Conditions

14.1 Acute Coronary Syndromes & Myocardial Infarction 14.2 Acute Chest Pain Risk Stratification & Triage 14.3 Acute or Critical Valvular Heart Emergencies

15 Chapter 15: Cardiac Arrhythmias, Heart Failure & Hypertensive Crises

15.1 Acute Atrial & Ventricular Arrhythmias 15.2 Acute Decompensated Heart Failure & Cardiogenic Shock 15.3 Hypertensive Emergency & Urgency Management

16 Chapter 16: Vascular & Thromboembolic Emergencies

16.1 Pulmonary Embolism & Deep Vein Thrombosis 16.2 Acute Aortic Syndromes & Peripheral Vascular Emergencies 16.3 Critical Limb Ischemia & Acute Arterial Occlusion

17 Chapter 17: Neurologic Emergencies: Stroke & Altered Consciousness

17.1 Acute Ischemic Stroke & Intracranial Hemorrhage 17.2 Syncope Evaluation & Status Epilepticus 17.3 Acute Delirium, Encephalopathy & Severe Confusion

18 Chapter 18: Neurologic Trauma & Acute Cranial Emergencies

18.1 Concussion, Moderate-to-Severe TBI & Intracranial Injury 18.2 Thunderclap & Acute Severe Secondary Headaches 18.3 Acute Ophthalmologic Emergencies

19 Chapter 19: Acute Abdominal, Pelvic & Gastrointestinal Emergencies

19.1 Acute Abdominal & Pelvic Pain Triage 19.2 Upper & Lower Gastrointestinal Bleeding 19.3 Acute Hepatic Failure, Cholangitis & Severe Jaundice

20 Chapter 20: Acute Pulmonary & Airway Emergencies

20.1 Acute Hypoxic Respiratory Failure & ARDS 20.2 Severe Community-Acquired Pneumonia & Empyema 20.3 Acute Severe Epistaxis & Airway Obstruction

21 Chapter 21: Acute Traumatic Injuries & Wound Care

21.1 Major Trauma Resuscitation & Initial Assessment 21.2 Burn Assessment, Inhalation Injury & Resuscitation 21.3 Laceration Management, Complex Wounds & Animal Bites

22 Chapter 22: Acute Orthopedic & Musculoskeletal Emergencies

22.1 Acute Ambulatory Fractures & Initial Splinting 22.2 Compartment Syndrome & Major Orthopedic Trauma 22.3 Septic Arthritis & Acute Microcrystalline Crises

23 Chapter 23: Severe Infections, Sepsis & Systemic Emergencies

23.1 Sepsis, Septic Shock & Initial Fluid Resuscitation 23.2 Necrotizing Soft Tissue Infections & Severe CNS Infections 23.3 Anaphylaxis Diagnosis, Epinephrine Dosing & Airway Protection

24 Chapter 24: Metabolic, Endocrine & Electrolyte Emergencies

24.1 Diabetic Ketoacidosis & Hyperosmolar Hyperglycemic State 24.2 Critical Electrolyte Emergencies: Dyskalemias & Dysnatremias 24.3 Severe Calcium Abnormalities & Acute Adrenal Crisis

25 Chapter 25: Hematologic, Urologic & Dental Emergencies

25.1 Severe Symptomatic Anemias & Coagulopathic Emergencies 25.2 Testicular Torsion, Priapism & Acute Urinary Retention 25.3 Urgent Odontogenic Infections & Dental Trauma

26 Chapter 26: Psychiatric, Behavioral & Obstetric/Gynecologic Emergencies

26.1 Suicidal Ideation, Acute Agitation & Behavioral Emergencies 26.2 Acute Physical & Sexual Assault Care 26.3 Life-Threatening Vaginal Bleeding & Ectopic Pregnancy 26.4 Environmental Heat Stroke & Severe Hypothermia

27 Chapter 27: Acute Head, Neck & Neurologic Symptoms

27.1 Primary Acute Headaches: Migraine, Tension & Cluster 27.2 Concussion & Minor Closed Head Injury Evaluation 27.3 Transient Ischemic Attack Evaluation & ABCD2 Risk Scoring

28 Chapter 28: Acute Cranial Nerves, Hearing & Sensory Symptoms

28.1 Peripheral Neuropathies: Bell's Palsy, Carpal Tunnel & Radiculopathy 28.2 Acute Tinnitus, Sudden Sensorineural Hearing Loss & Cerumen Impaction 28.3 Acute Dizziness, Benign Paroxysmal Positional Vertigo & Vestibular Neuritis

29 Chapter 29: Acute Upper Respiratory Tract Infections

29.1 Acute Viral Rhinosinusitis vs. Bacterial Rhinosinusitis 29.2 Acute Pharyngitis: Group A Streptococcus & Centor Criteria 29.3 Acute Otitis Media, Otitis Externa & Serous Effusion

30 Chapter 30: Acute Lower Respiratory Infections & Cough

30.1 Influenza, COVID-19 & Viral Respiratory Syndromes 30.2 Acute Bronchitis & Lower Respiratory Tract Infections 30.3 Ambulatory Community-Acquired Pneumonia

31 Chapter 31: Allergic, Nasal & Non-Infectious Pulmonary Conditions

31.1 Allergic Rhinitis & Acute Non-Anaphylactic Allergic Reactions 31.2 Acute Dyspnea in Ambulatory Care 31.3 Interstitial Lung Diseases & Sarcoidosis Presentation

32 Chapter 32: Acute Chest, Cardiac & Vascular Symptoms

32.1 Palpitations Evaluation & Arrhythmia Triage in Primary Care 32.2 Deep Vein Thrombosis & Superficial Thrombophlebitis 32.3 Ambulatory Hypotension & Orthostasis Evaluation

33 Chapter 33: Acute Upper Gastrointestinal Conditions

33.1 Peptic Ulcer Disease & Gastritis 33.2 Dysphagia, Esophagitis & Acute Esophageal Disorders 33.3 Acute Nausea, Vomiting & Foodborne Illness

34 Chapter 34: Acute Lower Gastrointestinal Conditions

34.1 Acute Infectious Diarrhea & Gastroenteritis 34.2 Acute Constipation & Functional Bowel Changes 34.3 Ano-Rectal Disorders: Hemorrhoids, Fissures, Abscesses & Pruritus Ani

35 Chapter 35: Inflammatory, Functional & Malabsorptive GI Disorders

35.1 Acute Flares of Inflammatory Bowel Disease 35.2 Irritable Bowel Syndrome: Diagnosis, Subtyping & Management 35.3 Celiac Disease & Malabsorption Syndromes

36 Chapter 36: Acute Abdominal, Hepatic & Biliary Disorders

36.1 Ambulatory Abdominal & Pelvic Pain Triage 36.2 Acute Cholecystitis, Biliary Colic & Pancreatitis 36.3 Acute Liver Injury & Viral Hepatitis

37 Chapter 37: Acute Abdominal Wall, Hernias & Dental Conditions

37.1 Abdominal Wall, Inguinal & Ventral Hernias 37.2 Acute Dental Pain, Odontogenic Abscess & Aphthous Ulcers 37.3 Acute Edema: Unilateral vs. Bilateral Diagnostic Evaluation

38 Chapter 38: Acute Infectious Dermatoses

38.1 Bacterial Skin Infections: Impetigo, Cellulitis & Cutaneous Abscesses 38.2 Fungal Skin Infections: Tinea Corporis, Cruris, Pedis & Onychomycosis 38.3 Viral Cutaneous Infections: Herpes Simplex, Zoster & Molluscum Contagiosum

39 Chapter 39: Inflammatory, Allergic & Autoimmune Dermatoses

39.1 Atopic Dermatitis, Contact Dermatitis & Eczematous Flares 39.2 Non-Infectious Rashes: Urticaria, Drug Eruptions & Erythema Multiforme 39.3 Cutaneous Malignancies & Premalignant Lesions: AK, BCC, SCC & Melanoma

40 Chapter 40: Acute Shoulder, Elbow & Upper Extremity Injuries

40.1 Rotator Cuff Pathology, Tendinopathy & Shoulder Impingement 40.2 Lateral & Medial Epicondylitis, Olecranon Bursitis & Elbow Sprains 40.3 Wrist & Hand Soft-Tissue Injuries: De Quervain, TFCC & Finger Sprains

41 Chapter 41: Acute Knee, Ankle & Lower Extremity Injuries

41.1 Meniscal Tears, Ligamentous Knee Injuries & Patellofemoral Pain 41.2 Ankle Sprains, Ottawa Ankle Rules & Achilles Tendinopathy 41.3 Plantar Fasciitis, Shin Splints & Overuse Syndromes

42 Chapter 42: Acute Ambulatory Fractures & Dislocations

42.1 Distal Radius, Scaphoid & Common Upper Extremity Fractures 42.2 Metatarsal, Clavicle & Common Lower Extremity Fractures 42.3 Joint Dislocation Management: Nursemaid's Elbow & Shoulder Subluxation

43 Chapter 43: Acute Axial Musculoskeletal Pain & Falls

43.1 Acute Low Back Pain: Red Flags, Strain & Disc Herniation 43.2 Acute Cervical Strain, Whiplash & Axial Neck Pain 43.3 Evaluation of Falls in Ambulatory & Older Patients

44 Chapter 44: Acute Inflammatory Arthropathies & Generalized Pain

44.1 Acute Inflammatory Arthritis & Spondyloarthropathies 44.2 Myalgias, Rhabdomyolysis & Post-Viral Pain Syndromes 44.3 Acute Non-Headache Pain Management Strategies

45 Chapter 45: Acute Renal, Urinary & Genitourinary Conditions

45.1 Uncomplicated UTI, Pyelonephritis & Acute Urethritis 45.2 Hematuria Workup & Glomerulonephritis 45.3 Nephrolithiasis & Acute Urinary Tract Obstruction

46 Chapter 46: Acute Male Genitourinary & Prostatic Conditions

46.1 Acute Prostatitis, Epididymitis & Orchitis 46.2 Acute Scrotal Pain: Torsion vs Appendage, BPH & Male Genital Emergencies 46.3 Acute Urinary Retention & Incontinence Evaluation

47 Chapter 47: Acute Women's Health & Early Pregnancy Care

47.1 Early Pregnancy Diagnosis, Dating & Initial Complications 47.2 Abnormal Uterine Bleeding & Acute Menstrual Disorders 47.3 Premenstrual Syndrome & Premenstrual Dysphoric Disorder

48 Chapter 48: Breast Disorders, STIs & Pediatric Elimination

48.1 Palpable Breast Mass, Mastitis & Nipple Discharge 48.2 Sexually Transmitted Infections: Diagnosis, Staging & CDC Guidelines 48.3 Pediatric Enuresis & Encopresis

49 Chapter 49: Systemic Signs, Metabolic Dysregulation & Miscellaneous Infections

49.1 Acute Fever, Sepsis Screening & FUO in Primary Care 49.2 Acute Hyperglycemia & Symptomatic Hypoglycemia 49.3 Electrolyte Abnormalities: Mild-to-Moderate Disturbances 49.4 Vector-Borne, Tick-Borne & Rickettsial Illnesses

50 Chapter 50: Chronic Cardiovascular Diseases: Hypertension & Ischemia

50.1 Essential Hypertension Management: 2025 AHA/ACC Guideline & JNC Strategies 50.2 Chronic Coronary Artery Disease & Post-MI Secondary Prevention 50.3 Chronic Heart Failure: HFrEF, HFpEF & Quadruple GDMT

51 Chapter 51: Chronic Vascular, Valvular & Dyslipidemic Diseases

51.1 Peripheral Arterial Disease & Claudication 51.2 Chronic Valvular Heart Disease & Murmur Evaluation 51.3 Lipid Disorders & ASCVD Risk-Based Statin Therapy

52 Chapter 52: Chronic Respiratory Diseases: Asthma & COPD

52.1 Chronic Asthma Management: GINA Stepwise SMART Therapy 52.2 Chronic Obstructive Pulmonary Disease: GOLD Recommendations 52.3 Solitary Pulmonary Nodule Evaluation & Fleischner Society Criteria

53 Chapter 53: Chronic Metabolic Diseases: Diabetes Mellitus

53.1 Type 2 Diabetes Management: ADA Pharmacotherapy Algorithms 53.2 Type 1 Diabetes: Basal-Bolus Insulin, CGMs & Diabetic Complications 53.3 Diabetic Microvascular & Macrovascular Disease Surveillance

54 Chapter 54: Obesity, Nutrition & Metabolic Bone Diseases

54.1 Medical & Behavioral Management of Obesity & Incretin Mimetics 54.2 Osteoporosis & Metabolic Bone Disease: DEXA, FRAX & Antiresorptives 54.3 Nutritional Deficiencies: Vitamin D, B12, Iron & Malnutrition

55 Chapter 55: Chronic Endocrine Disorders

55.1 Primary & Subclinical Hypothyroidism, Hyperthyroidism & Nodules 55.2 Adrenal Disorders: Addison's Disease & Cushing's Syndrome 55.3 Hypercalcemia, Hyperparathyroidism & Pituitary Disorders

56 Chapter 56: Chronic Kidney Disease & Venous Disorders

56.1 Chronic Kidney Disease: KDIGO Staging & Renoprotective Therapy 56.2 Chronic Venous Insufficiency, Stasis Dermatitis & Lymphedema 56.3 Chronic Electrolyte & Acid-Base Management in CKD

57 Chapter 57: Chronic Gastrointestinal & Hepatic Diseases

57.1 Gastroesophageal Reflux Disease, Barrett's Esophagus & Dyspepsia 57.2 Chronic Liver Disease: MASLD/NAFLD, Cirrhosis & Portal Hypertension 57.3 Viral Hepatitis B & C: Long-Term Monitoring & DAA Therapy

58 Chapter 58: Colorectal Surveillance & Chronic Pancreaticobiliary Care

58.1 Post-Polypectomy Colorectal Polyp Surveillance Guidelines 58.2 Chronic Pancreatitis & Exocrine Pancreatic Insufficiency 58.3 Chronic Nausea, Gastroparesis & Functional GI Disorders

59 Chapter 59: Chronic Musculoskeletal & Rheumatologic Disorders

59.1 Osteoarthritis: Hip, Knee & Hand Management 59.2 Spinal Conditions: Spinal Stenosis, Spondylolisthesis & Compression Fractures 59.3 Chronic Myopathies & Fibromyalgia Syndrome

60 Chapter 60: Chronic Neurologic & Neurodegenerative Disorders

60.1 Dementia: Alzheimer's, Vascular & Lewy Body Disease 60.2 Parkinson's Disease & Essential Tremor 60.3 Epilepsy: Chronic Antiseizure Medications & Post-Stroke Care

61 Chapter 61: Chronic Peripheral Nerves, Pain & Sensory Disorders

61.1 Diabetic & Chronic Peripheral Neuropathies 61.2 Chronic Pain Syndromes & Chronic Daily Headaches 61.3 Chronic Tinnitus, Presbycusis & Persistent Dizziness

62 Chapter 62: Chronic Psychiatric Disorders

62.1 Major Depressive Disorder & Generalized Anxiety Disorder 62.2 Bipolar Disorder: Maintenance Pharmacotherapy & Lithium Monitoring 62.3 Adult & Pediatric Attention-Deficit/Hyperactivity Disorder

63 Chapter 63: Chronic Behavioral Health & Neurodevelopmental Conditions

63.1 Chronic Behavioral Conditions: PTSD, OCD & Somatization 63.2 Autism Spectrum Disorder & Intellectual Disabilities 63.3 Eating Disorders: Anorexia Nervosa, Bulimia & Binge Eating

64 Chapter 64: Chronic Substance Use Disorders & Tobacco Cessation

64.1 Alcohol Use Disorder: Pharmacotherapy & Relapse Prevention 64.2 Opioid & Stimulant Use Disorders: MOUD & Harm Reduction 64.3 Longitudinal Tobacco Cessation Pharmacotherapy

65 Chapter 65: Chronic Dermatologic Conditions

65.1 Acne Vulgaris, Rosacea & Seborrheic Dermatitis 65.2 Chronic Plaque Psoriasis & Biologic Therapies 65.3 Chronic Eczema, Hidradenitis Suppurativa & Cutaneous Lupus

66 Chapter 66: Chronic Reproductive, Infectious & Geriatric Special Care

66.1 Chronic Menstrual Disorders, Infertility & Sexual Dysfunction 66.2 Menopause Management & Hormone Replacement Therapy 66.3 Chronic HIV Infection Management & Primary Care Integration 66.4 Gender-Affirming Primary Care & Hormone Therapy 66.5 Advance Care Planning, Palliative Care & End-of-Life Symptom Control

67 Chapter 67: Continuity Care: Sleep, Fatigue, Cancer, Pregnancy & the Adult Preventive Visit

67.1 Chronic Insomnia & Obstructive Sleep Apnea 67.2 Chronic Malaise, Fatigue & ME/CFS 67.3 Primary Care During Cancer Treatment & Survivorship 67.4 Routine Prenatal Care & Longitudinal Pregnancy Management 67.5 The Periodic Adult Health Examination & Medicare Annual Wellness Visit

12.3 Bloodborne Infectious Disease Screening: HIV & Hepatitis C

Key Takeaways Explain This Topic AI

The USPSTF issues a Grade A recommendation for universal HIV screening in all adolescents and adults aged 15 to 65 years, all pregnant individuals during each pregnancy, and persons outside this age range who are at increased risk.

The CDC/CLSI HIV diagnostic algorithm begins with a 4th-generation combination immunoassay detecting HIV-1/2 antibodies and HIV-1 p24 antigen, reflexing to an HIV-1/HIV-2 antibody differentiation immunoassay, with discordant or indeterminate results resolved by quantitative or qualitative HIV-1 RNA NAAT.

Acute Retroviral Syndrome (primary HIV) presents 2 to 4 weeks post-exposure as a severe mononucleosis-like illness with extremely high plasma viral loads (>100,000 to millions of copies/mL); during early acute infection, 4th-generation antibody differentiation tests are non-reactive or indeterminate while HIV-1 RNA PCR is strongly positive.

Universal Hepatitis C screening (USPSTF Grade A) is recommended at least once in a lifetime for all adults aged 18 to 79 years and for all pregnant persons during each pregnancy, utilizing anti-HCV antibody testing with mandatory automated reflex to HCV RNA PCR.

An anti-HCV positive / HCV RNA negative pattern indicates resolved past infection or successfully treated HCV; because anti-HCV antibodies persist for life without conferring immunity, suspected reinfection must be diagnosed by directly testing for HCV RNA PCR.

Last updated: September 2026

Universal HIV Screening: USPSTF Grade A Mandates

Human Immunodeficiency Virus (HIV) infection is a chronic bloodborne and sexually transmitted infection that causes progressive CD4+ T-lymphocyte depletion, cellular immune failure, and opportunistic illness. Early diagnosis and prompt initiation of Antiretroviral Therapy (ART) suppress viral replication, halt disease progression, restore normal life expectancy, and eliminate sexual transmission ( Undetectable = Untransmittable [U=U] ).

The USPSTF Recommendations

Universal Screening (Ages 15 to 65 Years; Grade A) : The USPSTF recommends that clinicians screen for HIV infection in all adolescents and adults aged 15 to 65 years , regardless of reported risk behaviors or clinical presentation. Routine opt-out screening normalizes testing, reduces social stigma, and identifies the estimated 13% of individuals living with HIV who are unaware of their infection.

Universal Screening in Pregnancy (Grade A) : Universal HIV screening is recommended for all pregnant persons during each pregnancy , ideally at the initial prenatal visit. For individuals at high risk of HIV acquisition (e.g., PWID, partners living with HIV, commercial sex work, new STI diagnosis during pregnancy, or residing in high-prevalence areas), screening must be repeated during the third trimester (prior to 36 weeks gestation). Immediate rapid testing during labor and delivery is mandated for individuals whose HIV status is undocumented.

High-Risk Individuals Outside Ages 15 to 65 (Grade A) : Screen persons younger than 15 or older than 65 who exhibit increased risk factors (new or multiple partners, injection drug use, MSM, transactional sex).

Screening Frequency for High-Risk Populations : Individuals at ongoing high risk—such as sexually active MSM, transgender individuals having condomless sex, PWID sharing injection paraphernalia, and commercial sex workers—should undergo screening at least annually, and as often as every 3 to 6 months .

Opt-Out Consent Paradigm : HIV testing should be conducted using an opt-out model : the patient is notified verbally or in writing that HIV testing will be performed as part of routine preventive labs unless the patient explicitly declines. Formal separate written consent is no longer recommended by the CDC, as it creates administrative barriers to universal testing.

The CDC / CLSI 4th-Generation HIV Diagnostic Algorithm

Modern clinical practice utilizes the Centers for Disease Control and Prevention and Clinical and Laboratory Standards Institute (CDC/CLSI) standardized diagnostic cascade, which replaced older Western blot algorithms: STEP 1: 4th-Generation HIV-1/2 Combination Immunoassay

• (Detects HIV-1/2 Antibodies & HIV-1 p24 Antigen)
• |
• +---------+---------+
• | |
• NON-REACTIVE REACTIVE
• | |
• HIV Negative v
• (Unless acute window STEP 2: HIV-1 / HIV-2 Antibody Differentiation Immunoassay
• suspected; check RNA) |
• +-------------------+-------------------+
• | | |
• HIV-1 (+) HIV-2 (+) BOTH (-) OR INDETERMINATE
• | | |
• HIV-1 Infection HIV-2 Infection v
• Confirmed Confirmed STEP 3: Qualitative / Quantitative
• HIV-1 RNA NAAT
• |
• +---------+---------+
• | |
• DETECTABLE UNDETECTABLE
• | |
• ACUTE HIV-1 FALSE-POSITIVE
• INFECTION SCREENING TEST
• (p24(+) / Ab(-)) (HIV Negative)
• Detailed Breakdown of Algorithm Steps

Step 1: 4th-Generation Combination Immunoassay :

Detects both HIV-1 and HIV-2 antibodies (IgM and IgG) AND the HIV-1 p24 capsid antigen .

The Diagnostic Advantage : Free viral p24 antigen appears in the bloodstream within 14 to 20 days post-infection , significantly earlier than host IgG antibodies (which develop at 30 to 45 days). This test narrows the diagnostic "window period" to approximately 2 to 3 weeks.

If non-reactive: The patient is considered HIV-negative. (Caveat: If the patient reports a high-risk exposure within the preceding 14 days, the test may be in the pre-p24 eclipse window; order an HIV-1 RNA NAAT immediately). If reactive, reflex directly to Step 2.

Step 2: HIV-1 / HIV-2 Antibody Differentiation Immunoassay :

Rapid, multi-spot instrument immunoassay that discriminates whether reactive antibodies are directed against HIV-1 or HIV-2.

Clinical Distinction : Identifying HIV-2 is clinically vital: HIV-2 is endemic to West Africa and is intrinsically resistant to Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) and has decreased susceptibility to certain protease inhibitors.

If reactive for HIV-1 or HIV-2 antibodies: Diagnosis is established.

If non-reactive or indeterminate for both antibodies : Proceed directly to Step 3.

Step 3: HIV-1 RNA Nucleic Acid Amplification Test (NAAT) :

Detects viral RNA genetic material (qualitative or quantitative viral load).

Scenario A (HIV-1 RNA Detectable) : Confirms Acute HIV-1 Infection (the p24 antigen was detected in Step 1, but host antibodies have not yet formed in Step 2).

Scenario B (HIV-1 RNA Undetectable) : Confirms that the initial Step 1 immunoassay was a biological false positive . The patient is uninfected.

Acute Retroviral Syndrome (Primary HIV Infection)

Acute Retroviral Syndrome (ARS) represents the initial symptomatic phase of HIV infection, occurring in 50% to 80% of individuals approximately 2 to 4 weeks after viral inoculation .

Clinical Presentation

ARS typically presents as a severe, prolonged mononucleosis-like illness characterized by:

High spiking fevers (96%) and severe fatigue.

Generalized, non-tender cervical, axillary, and occipital lymphadenopathy (74%).

Pharyngitis (70%), frequently non-exudative.

Maculopapular morbilliform rash (70%): An erythematous, non-pruritic maculopapular eruption prominently distributed across the face, neck, upper trunk, and occasionally the extremities, palms, and soles.

Severe myalgias and arthralgias (54%).

Painful mucocutaneous ulcerations (33%): Shallow, sharply demarcated aphthous-like ulcers on the oral mucosa, tongue, esophagus, or anogenital region.

Gastrointestinal symptoms: Nausea, vomiting, profuse watery diarrhea, and rapid weight loss.

Neurologic manifestations: Aseptic meningitis, facial palsy, or radiculopathy.

Diagnostic Biomarker Dynamics & Exam Pearls

Viremia Level : During ARS, viral replication is unconstrained by host cellular immunity; plasma HIV-1 RNA levels are massively elevated—routinely exceeding 100,000 to millions of copies/mL .

The Diagnostic Trap : A 3rd-generation antibody test will be completely non-reactive (negative) because host IgG seroconversion takes 3 to 6 weeks. A 4th-generation combination assay may be reactive due to p24 antigen, but the Step 2 differentiation assay will be negative. The single most sensitive and definitive diagnostic test for Acute Retroviral Syndrome is quantitative plasma HIV-1 RNA PCR (viral load) .

Board Exam Pearl : A young patient presents with high fever, sore throat, generalized lymphadenopathy, and a diffuse maculopapular rash. A heterophile antibody test (Monospot) is negative. The primary care physician must immediately ask about sexual and injection history and order an HIV-1 RNA NAAT to diagnose acute HIV, which is the most critical "Monospot-negative mono" lookalike!

Urgent Clinical Action : Immediate initiation of Antiretroviral Therapy (ART)—same-day or rapid start—preserves the latent CD4 cell reservoir, limits chronic immune activation, prevents opportunistic sequelae, and abruptly halts forward viral transmission.

Universal Hepatitis C Screening: USPSTF Grade A Mandates

Hepatitis C Virus (HCV) is a single-stranded RNA flavivirus transmitted predominantly through parenteral blood contact. Chronic infection develops in 75% to 85% of exposed individuals, leading to progressive hepatic fibrosis, cirrhosis, end-stage liver disease, and hepatocellular carcinoma (HCC).

The Screening Guidelines

Universal Screening for Adults Aged 18 to 79 Years (USPSTF Grade A) : The USPSTF recommends one-time universal screening for HCV infection in all adults aged 18 to 79 years, regardless of risk factors. This universal recommendation expanded upon the previous "baby boomer" birth cohort (1945–1965) strategy due to the dramatic surge in acute HCV infections among adolescents and young adults fueled by the opioid and injection drug epidemic.

Universal Screening in Pregnancy (USPSTF Grade A) : Screen all pregnant persons during each pregnancy , typically at the initial prenatal visit. Identifying maternal infection enables postpartum curative treatment and guides pediatric testing for infants at risk of vertical transmission.

Periodic / Annual Screening for Ongoing Risk : Individuals with persistent risk behaviors—such as ongoing injection drug use, intranasal illicit substance use, maintenance hemodialysis, men with HIV who have sex with men, commercial sex workers, and individuals who received unregulated tattoos or body piercings—must receive annual or more frequent HCV screening .

Hepatitis C Diagnostic Testing Cascade & Serologic Patterns

The diagnostic cascade for Hepatitis C requires an initial screening test followed by mandatory, automated molecular confirmation: INITIAL SCREENING: Anti-HCV Antibody Immunoassay

• |
• +---------+---------+
• | |
• NON-REACTIVE REACTIVE
• | |
• No Infection v
• (Unless acute window; MANDATORY REFLEX: Quantitative HCV RNA PCR
• check RNA if suspected) |
• +---------+---------+
• | |
• DETECTABLE UNDETECTABLE
• | |
• ACTIVE CHRONIC RESOLVED PAST
• HCV INFECTION INFECTION
• (Evaluate for DAA) (Or Treated HCV;
• Anti-HCV stays (+))
• Automated Reflex HCV RNA Testing

Clinicians should always order "HCV Antibody with Reflex to Quantitative HCV RNA." When the anti-HCV antibody is reactive, the laboratory automatically tests the original primary blood sample for HCV RNA PCR. This eliminates the catastrophic loss to follow-up (previously >30% to 50%) that occurred when patients were required to return for a separate venipuncture.

Master Interpretation Matrix: Hepatitis C Serologic Profiles

Diagnostic Pattern Anti-HCV Antibody HCV RNA PCR Clinical Interpretation & Mandatory Primary Care Actions

Active Chronic HCV Infection REACTIVE DETECTABLE Indicates active viremic infection (viral replication present). Mandatory steps: 1) Non-invasive fibrosis staging (FIB-4 score); 2) Screen for Hepatitis A and B (administer vaccines if non-immune); 3) Counsel on alcohol cessation; 4) Initiate curative Direct-Acting Antiviral (DAA) therapy.

Resolved Past Infection / Cured HCV REACTIVE UNDETECTABLE Represents either spontaneous immune clearance (occurs in 15% to 25% of individuals) OR successfully cured HCV following DAA therapy. No active viremia; patient cannot transmit HCV; DAA therapy is NOT indicated. Critical Pearl : Anti-HCV antibodies persist for life and provide zero protective immunity.

Acute HCV in Serologic Window Period NON-REACTIVE DETECTABLE Represents early acute Hepatitis C before host antibody seroconversion has occurred (the serologic window is typically 2 to 8 weeks, but can extend to 12 weeks). Suspected in healthcare workers post-needlestick or PWID presenting with acute transaminitis and jaundice.

No HCV Infection NON-REACTIVE UNDETECTABLE Patient is uninfected. If an acute parenteral exposure occurred within the past 4 weeks, repeat HCV RNA testing in 4 to 6 weeks.

The Clinical Problem of Suspected Reinfection

Because anti-HCV antibodies persist indefinitely, an anti-HCV antibody test is completely useless for diagnosing reinfection in a patient who has previously cleared or been cured of Hepatitis C. If a patient with prior cured HCV resumes injection drug use and presents with acute malaise or elevated transaminases, the clinician must bypass the antibody test and order quantitative HCV RNA PCR directly .

Primary Care Management of Active Hepatitis C

Once active viremia is documented (anti-HCV reactive + HCV RNA detectable), primary care physicians can easily manage and cure the infection using simplified treatment algorithms:

1. Non-Invasive Hepatic Fibrosis Assessment

Before prescribing DAAs, clinicians must determine whether the patient has progressed to cirrhosis (METAVIR stage F4):

FIB-4 Index : Validated mathematical calculator utilizing four simple parameters: FIB-4 = Age (years) × AST (U/L) Platelet Count ( 10 9 / L ) × ALT (U/L) \text{FIB-4} = \frac{\text{Age (years)} \times \text{AST (U/L)}}{\text{Platelet Count } (10^9/\text{L}) \times \sqrt{\text{ALT (U/L)}}} FIB-4 = Platelet Count ( 1 0 9 / L ) × ALT (U/L) ​ Age (years) × AST (U/L) ​

A calculated FIB-4 < 1.45 has a >90% negative predictive value for advanced fibrosis (F0–F2; non-cirrhotic).

A calculated FIB-4 > 3.25 has a 97% specificity for advanced fibrosis/cirrhosis (F3–F4).

Transient Elastography (FibroScan) : Measures liver stiffness in kilopascals (kPa). Values >=12.5 kPa indicate cirrhosis.

2. Pangenotypic Direct-Acting Antiviral (DAA) Regimens

Modern DAAs target non-structural viral proteins (NS3/4A protease inhibitors, NS5A replication complex inhibitors, and NS5B RNA-dependent RNA polymerase inhibitors). In treatment-naive patients without cirrhosis, two first-line pangenotypic regimens yield cure rates exceeding 95% to 98% :

Glecaprevir / Pibrentasvir (Mavyret) :

Dosing : 3 tablets taken orally once daily with food for exactly 8 weeks .

Composition : Glecaprevir (NS3/4A protease inhibitor, 100 mg per tablet) + Pibrentasvir (NS5A inhibitor, 40 mg per tablet).

Sofosbuvir / Velpatasvir (Epclusa) :

Dosing : 1 tablet taken orally once daily for exactly 12 weeks .

Composition : Sofosbuvir (NS5B nucleotide polymerase inhibitor, 400 mg) + Velpatasvir (NS5A inhibitor, 100 mg).

Drug Interaction Warning : Velpatasvir requires gastric acidity for oral absorption. Proton Pump Inhibitors (PPIs) severely decrease velpatasvir absorption and can cause treatment failure; PPIs must be withheld or taken 4 hours after Epclusa with food.

3. Sustained Virologic Response (SVR12) = Virologic Cure

The therapeutic goal of DAA therapy is Sustained Virologic Response at 12 weeks post-treatment (SVR12) , defined as an undetectable plasma HCV RNA level 12 weeks after completing the full antiviral course. Achieving SVR12 signifies definitive virologic cure, decreases all-cause mortality, and reduces the risk of hepatic failure.

4. Post-Cure Surveillance in Cirrhotic Patients

CRITICAL BOARD EXAM RULE: Cirrhosis Surveillance Continues for Life : If a patient had underlying cirrhosis (F4) prior to DAA treatment, achieving SVR12 virologic cure does NOT eliminate their risk of hepatocellular carcinoma (HCC) . Although the relative risk of HCC declines, the absolute annual risk remains >1% to 1.5% per year. Therefore, all patients with pre-existing cirrhosis must continue lifetime surveillance for hepatocellular carcinoma with abdominal ultrasound (with or without serum alpha-fetoprotein [AFP]) every 6 months , alongside periodic screening for esophageal varices via upper endoscopy.

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