HIV/AIDS for USMLE Step 1
HIV/AIDS for the USMLE Step 1 Exam
Epidemiology and Transmission
- Global Prevalence:
- Over 38 million people worldwide live with HIV/AIDS, with significant prevalence in sub-Saharan Africa.
- In the U.S., HIV predominantly affects men who have sex with men (MSM) but also occurs in heterosexual individuals and those who inject drugs.
- Transmission:
- Sexual Contact: Primary mode, with increased risk in receptive anal intercourse.
- Blood Exposure: Sharing needles among injection drug users or through transfusions (rare in countries with blood screening).
- Vertical Transmission: From mother to child during childbirth or breastfeeding if untreated.
Pathophysiology
- HIV Virus Structure:
- HIV is an RNA retrovirus with a viral envelope that binds to CD4 receptors on T cells.
- Core enzymes include reverse transcriptase, integrase, and protease, essential for viral replication and integration into the host genome.
- Viral Replication and Immune Evasion:
- The virus binds to CD4 and either CCR5 or CXCR4 co-receptors to enter host cells.
- Using reverse transcriptase, HIV converts its RNA into DNA, which integrates into the host DNA via integrase, allowing long-term infection.
- Continuous replication and immune evasion result in a gradual decline in CD4+ T cells, weakening immune defenses.
- Progression to AIDS:
- Acute HIV Infection: High viral load with flu-like symptoms, followed by partial immune recovery.
- Chronic HIV Infection: Asymptomatic or mild symptoms with ongoing viral replication and CD4+ decline.
- AIDS: Defined by CD4 <200 cells/µL or the presence of AIDS-defining illnesses, such as Pneumocystis jirovecii pneumonia or Kaposi sarcoma.
Clinical Presentation
- Acute Retroviral Syndrome:
- Occurs 2–4 weeks after exposure, presenting with fever, sore throat, lymphadenopathy, rash, and myalgia, resembling mononucleosis.
- Diagnosis in this phase is through HIV RNA PCR, as antibody tests may not yet detect infection.
- Chronic HIV Infection:
- Prolonged asymptomatic period, though some may develop mild symptoms like oral thrush or herpes zoster.
- CD4+ count gradually declines, increasing susceptibility to opportunistic infections.
- AIDS:
- Characterized by severe immunosuppression, with susceptibility to opportunistic infections (e.g., tuberculosis, candidiasis) and cancers (e.g., Kaposi sarcoma, non-Hodgkin lymphoma).
Diagnosis
- Initial Screening:
- Antigen/Antibody Combination Test: Fourth-generation assay detects both HIV antibodies and p24 antigen, allowing earlier detection.
- HIV RNA PCR: Used in suspected acute infection when antibodies may not yet be present.
- Confirmatory Testing:
- Confirmatory antibody testing or RNA testing to verify initial positive results.
- CD4 Count and Viral Load:
- CD4 Count: Indicates immune function and risk for opportunistic infections.
- Viral Load: Measures viral replication and guides treatment effectiveness.
Treatment
- Antiretroviral Therapy (ART):
- Goal: Suppress viral replication to undetectable levels, allowing CD4 recovery and reducing transmission.
- Drug Classes:
- Nucleoside Reverse Transcriptase Inhibitors (NRTIs): Tenofovir, emtricitabine.
- Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs): Efavirenz.
- Protease Inhibitors (PIs): Atazanavir, typically with a booster like ritonavir.
- Integrase Strand Transfer Inhibitors (INSTIs): Dolutegravir, preferred for first-line therapy due to high efficacy.
- ART Regimen: Often a combination of NRTIs with an INSTI for initial therapy.
- Prophylaxis for Opportunistic Infections:
- PCP (Pneumocystis jirovecii Pneumonia): TMP-SMX prophylaxis when CD4 <200 cells/µL.
- Toxoplasmosis: TMP-SMX when CD4 <100 cells/µL and positive Toxoplasma IgG.
- MAC (Mycobacterium avium Complex): Azithromycin when CD4 <50 cells/µL.
Key Points
- HIV is an RNA retrovirus targeting CD4+ T cells, leading to progressive immune system compromise and risk for opportunistic infections.
- Transmission occurs primarily through sexual contact, blood exposure, and from mother to child.
- Acute HIV presents with flu-like symptoms, while chronic infection is often asymptomatic until CD4+ levels are critically low.
- Diagnosis involves an antigen/antibody combination test, confirmed by RNA or antibody testing.
- ART is essential to suppress viral replication, improve immune function, and reduce transmission risk.
- Opportunistic infection prophylaxis depends on CD4 count, with TMP-SMX, azithromycin, and other agents used based on risk level.