HIV/AIDS for USMLE Step 3
HIV/AIDS for the USMLE Step 3 Exam
Epidemiology and Transmission
- Prevalence:
- HIV/AIDS affects over 38 million people worldwide, with approximately 1 million cases in the U.S.
- Groups at higher risk include MSM (men who have sex with men), injection drug users (IDUs), and individuals with multiple sexual partners or unprotected sex practices.
- Transmission:
- Sexual Contact: Primary transmission route, with increased risk in receptive anal intercourse.
- Blood Exposure: Needle sharing and healthcare-related exposure.
- Vertical Transmission: From mother to child during pregnancy, delivery, or breastfeeding, particularly without ART.
Pathophysiology
- HIV Structure and Mechanism:
- HIV is an RNA retrovirus that binds to CD4 and co-receptors (CCR5 or CXCR4) to infect CD4+ T cells.
- HIV uses reverse transcriptase to convert RNA to DNA, which integrates into the host genome, establishing a persistent infection.
- Immune System Impact:
- Acute infection results in high viral load and rapid CD4 decline, with partial CD4 recovery as the infection becomes chronic.
- Chronic infection leads to ongoing immune activation and CD4 cell loss, eventually progressing to AIDS (CD4 <200 cells/µL or the presence of AIDS-defining illnesses).
Clinical Stages
- Acute Retroviral Syndrome:
- Presents 2–4 weeks after infection with fever, lymphadenopathy, sore throat, rash, and myalgia.
- Diagnosis in this phase is confirmed by HIV RNA PCR, as antibodies may not yet be detectable.
- Chronic HIV Infection:
- Latent phase with gradual CD4+ decline; may be asymptomatic or have mild symptoms (e.g., oral candidiasis, herpes zoster).
- Without ART, disease progresses to AIDS.
- AIDS:
- Characterized by severe immunosuppression, with susceptibility to opportunistic infections (e.g., Pneumocystis pneumonia, tuberculosis) and malignancies (e.g., Kaposi sarcoma).
Diagnosis
- Screening:
- Antigen/Antibody Combination Test: Fourth-generation assay detects both p24 antigen and HIV antibodies, identifying early infection.
- HIV RNA PCR: Useful for acute infection or if antigen/antibody test is inconclusive.
- Confirmatory Testing:
- HIV-1/HIV-2 Antibody Differentiation Immunoassay: Confirms positive results and distinguishes HIV-1 from HIV-2.
- CD4 Count and Viral Load:
- CD4 Count: Assesses immune function and guides prophylaxis for opportunistic infections.
- Viral Load: Monitors infection status and ART effectiveness.
Treatment
- Antiretroviral Therapy (ART):
- Goal: Suppress viral load, increase CD4 counts, reduce transmission, and prevent progression to AIDS.
- Drug Classes:
- NRTIs (Nucleoside Reverse Transcriptase Inhibitors): Tenofovir, emtricitabine.
- INSTIs (Integrase Strand Transfer Inhibitors): Dolutegravir, bictegravir, often first-line due to efficacy and low side effects.
- NNRTIs (Non-Nucleoside Reverse Transcriptase Inhibitors) and PIs (Protease Inhibitors): Alternative or additional options based on resistance and tolerance.
- ART Regimen: Combination of NRTIs with an INSTI or other agents depending on resistance and patient tolerance.
- Prophylaxis for Opportunistic Infections:
- PCP (Pneumocystis jirovecii Pneumonia): TMP-SMX when CD4 <200 cells/µL.
- Toxoplasmosis: TMP-SMX when CD4 <100 cells/µL and positive Toxoplasma IgG.
- MAC (Mycobacterium avium Complex): Azithromycin for CD4 <50 cells/µL.
Preventive Strategies
- Pre-Exposure Prophylaxis (PrEP):
- Indicated for HIV-negative individuals at high risk (e.g., MSM, serodiscordant couples).
- Regimen: Tenofovir/emtricitabine (Truvada) daily.
- Post-Exposure Prophylaxis (PEP):
- Recommended following potential exposure, such as a needlestick injury or unprotected sex.
- Regimen: 28-day course of ART, initiated within 72 hours.
- Vertical Transmission Prevention:
- During Pregnancy and Delivery: ART for HIV-positive mothers; IV zidovudine for mothers with detectable viral load.
- Infant Prophylaxis: Zidovudine for neonates to reduce transmission risk.
Key Points
- HIV targets CD4+ T cells, progressively depleting them and leading to immune deficiency.
- Transmission occurs through sexual contact, blood exposure, and vertical transmission.
- Acute HIV presents with flu-like symptoms; chronic infection may remain asymptomatic until CD4 levels fall.
- Diagnosis includes a fourth-generation antigen/antibody test, confirmed by RNA or antibody differentiation testing.
- ART, combining NRTIs and an INSTI, is recommended for all HIV-positive individuals to suppress viral replication and reduce transmission.
- Opportunistic infection prophylaxis is based on CD4 count, with agents like TMP-SMX and azithromycin used for specific thresholds.
- PrEP, PEP, and ART during pregnancy are crucial for reducing transmission risk.