HIV/AIDS for USMLE Step 2
HIV/AIDS for the USMLE Step 2 Exam
Epidemiology and Transmission
- Global and U.S. Prevalence:
- Over 38 million people worldwide are living with HIV/AIDS, with approximately 1 million in the U.S.
- HIV affects individuals across all demographics, with MSM (men who have sex with men), heterosexual individuals with high-risk behaviors, and injection drug users (IDUs) at particularly high risk.
- Transmission Modes:
- Sexual Contact: Primary transmission route, with risk increased in anal intercourse and unprotected sex.
- Blood Exposure: Needle sharing among IDUs and accidental needlestick injuries in healthcare.
- Vertical Transmission: Mother to child during pregnancy, delivery, or breastfeeding if untreated.
Pathophysiology
- HIV Structure and Target:
- HIV is an RNA retrovirus that infects CD4+ T cells, leading to immune system compromise.
- The virus binds to CD4 receptors and co-receptors (CCR5 or CXCR4) to enter the cell, using reverse transcriptase to convert RNA to DNA, which then integrates into the host genome.
- Immune Evasion and Disease Progression:
- Acute Infection: Initial high viral replication and CD4 decline, presenting with flu-like symptoms.
- Chronic HIV: Latent period with gradual CD4+ decline and mild symptoms (oral thrush, herpes zoster).
- AIDS: Severe immunosuppression defined by CD4 <200 cells/µL or an AIDS-defining illness (e.g., Pneumocystis jirovecii pneumonia, Kaposi sarcoma).
Clinical Presentation
- Acute Retroviral Syndrome:
- Presents 2–4 weeks after infection with fever, lymphadenopathy, sore throat, rash, and myalgia.
- High viral load and transient drop in CD4, diagnosed by HIV RNA PCR.
- Chronic HIV Infection:
- Asymptomatic or mild symptoms during this phase, which may last for years.
- As CD4 declines, susceptibility to opportunistic infections increases, progressing to AIDS if untreated.
- AIDS-Defining Illnesses:
- Opportunistic Infections: Pneumocystis pneumonia, cryptococcal meningitis, cytomegalovirus (CMV) retinitis.
- Malignancies: Kaposi sarcoma, non-Hodgkin lymphoma.
Diagnosis
- Initial Screening:
- Antigen/Antibody Combination Test: Detects both HIV antibodies and p24 antigen, allowing early detection.
- HIV RNA PCR: Detects viral RNA, useful in acute infection when antibodies may not yet be present.
- Confirmatory Testing:
- HIV-1/HIV-2 Antibody Differentiation Immunoassay: Confirms infection and distinguishes between HIV-1 and HIV-2.
- CD4 Count and Viral Load: CD4 indicates immune status, while viral load assesses infection severity and ART response.
Treatment
- Antiretroviral Therapy (ART):
- Goals: Suppress viral replication, restore immune function, reduce transmission, and prevent AIDS.
- ART Components:
- NRTIs: Tenofovir and emtricitabine are commonly used backbones.
- INSTIs: Dolutegravir and bictegravir are preferred initial agents due to efficacy and tolerability.
- NNRTIs and PIs: Alternative agents depending on resistance, side effects, and drug interactions.
- Initiation: Recommended for all HIV-positive individuals regardless of CD4 count, ideally immediately after diagnosis to prevent immune deterioration.
- Prophylaxis for Opportunistic Infections:
- PCP (Pneumocystis jirovecii Pneumonia): TMP-SMX when CD4 <200 cells/µL.
- Toxoplasmosis: TMP-SMX for CD4 <100 cells/µL and positive Toxoplasma IgG.
- MAC (Mycobacterium avium Complex): Azithromycin for CD4 <50 cells/µL.
Preventive Strategies
- Pre-Exposure Prophylaxis (PrEP):
- Indications: HIV-negative individuals at high risk, including MSM, IDUs, and serodiscordant partners.
- Regimen: Daily oral tenofovir/emtricitabine (Truvada), shown to significantly reduce HIV transmission risk.
- Post-Exposure Prophylaxis (PEP):
- Indications: Following potential HIV exposure (e.g., needlestick injuries or unprotected sex).
- Regimen: 28-day ART regimen, ideally initiated within 72 hours of exposure.
- Prevention of Vertical Transmission:
- Management: ART for HIV-positive mothers during pregnancy, labor, and delivery, and avoidance of breastfeeding.
- Neonatal Prophylaxis: Zidovudine for infants born to HIV-positive mothers.
Key Points
- HIV is an RNA retrovirus that targets CD4+ T cells, leading to progressive immune suppression.
- Transmission occurs mainly through sexual contact, blood exposure, and vertical routes.
- Acute HIV infection presents with flu-like symptoms; chronic infection may be asymptomatic until immunodeficiency advances to AIDS.
- Diagnosis involves antigen/antibody testing confirmed by viral RNA testing.
- ART is recommended for all HIV-positive patients, with NRTI and INSTI combinations as preferred first-line regimens.
- Opportunistic infection prophylaxis is guided by CD4 count, with TMP-SMX, azithromycin, and other agents based on specific risks.
- PrEP, PEP, and careful management during pregnancy are effective preventive strategies.