HIV/AIDS for ABIM

HIV/AIDS for the American Board of Internal Medicine Exam

• Prevalence:
• Approximately 38 million people globally and over 1 million in the United States are living with HIV/AIDS.
• HIV is transmitted primarily through unprotected sexual contact, injection drug use, vertical transmission (mother to child), and exposure to infected blood or bodily fluids.

• Risk Factors:
• Sexual Contact: High-risk behaviors include unprotected intercourse, particularly among men who have sex with men (MSM) and heterosexuals with multiple partners.
• Injection Drug Use: Sharing needles or equipment.
• Healthcare Exposure: Occupational exposure through needlesticks or contact with blood.
• Vertical Transmission: From mother to child during pregnancy, childbirth, or breastfeeding.
• Geographic and Socioeconomic Factors: Higher rates in low-resource settings and populations with limited healthcare access.

• Virus Structure and Replication:
• HIV is an RNA retrovirus primarily targeting CD4+ T cells.
• The virus binds to CD4 receptors and co-receptors (CCR5 or CXCR4), entering the host cell, where it uses reverse transcriptase to convert RNA into DNA.
• Viral DNA integrates into the host genome via integrase, leading to chronic infection and eventual T-cell depletion.

• Immune System Impact:
• Progressive depletion of CD4+ T cells impairs immune response, increasing susceptibility to opportunistic infections (OIs) and malignancies.
• Acute infection leads to a transient decrease in CD4+ cells, followed by partial recovery as the virus establishes latency.
• Without treatment, chronic immune activation and cell destruction ultimately progress to AIDS (CD4 <200 cells/µL or the presence of AIDS-defining conditions).

• Acute HIV Infection:
• Symptoms: Fever, sore throat, lymphadenopathy, myalgia, and maculopapular rash, similar to mononucleosis or flu.
• Viral Load: High, with rapid viral replication and dissemination throughout the body.
• Diagnosis: HIV RNA PCR or fourth-generation antigen/antibody testing as antibody tests may be negative initially.

• Chronic HIV Infection:
• Asymptomatic Phase: Lasts years with slow CD4+ decline; patients may be unaware of infection.
• Symptomatic Phase: As CD4 count decreases, patients may experience mild infections (e.g., herpes zoster, candidiasis).

• AIDS:
• Definition: CD4 <200 cells/µL or the presence of AIDS-defining illnesses (e.g., Pneumocystis jirovecii pneumonia, Kaposi sarcoma).
• Symptoms: Severe immunosuppression and susceptibility to opportunistic infections and certain cancers.

• Screening:
• Antigen/Antibody Combination Tests: Fourth-generation assays detect HIV-1/2 antibodies and p24 antigen, enabling early diagnosis.
• HIV RNA PCR: Useful in acute HIV and early infection when antibodies may not be present.

• Confirmatory Testing:
• Western Blot or Immunoassay: Confirms HIV antibodies; Western blot is less commonly used due to long window period.
• Viral Load Testing: Monitors infection severity and response to treatment.

• Monitoring:
• CD4 Count: Assesses immune status and guides opportunistic infection prophylaxis.
• HIV Viral Load: Measures viral replication and assesses treatment efficacy.

• Antiretroviral Therapy (ART):
• Goals: Suppress viral load to undetectable levels, preserve immune function, prevent transmission, and reduce morbidity/mortality.
• Initiation: Recommended for all HIV-infected individuals regardless of CD4 count; immediate initiation in acute infection provides benefits in immune recovery and reduces transmission.

• ART Regimens:
• Nucleoside Reverse Transcriptase Inhibitors (NRTIs): Tenofovir, emtricitabine, lamivudine. Backbone of most ART regimens.
• Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs): Efavirenz, rilpivirine. Commonly used in initial therapy but with caution due to drug resistance.
• Protease Inhibitors (PIs): Atazanavir, darunavir. Often combined with a booster (ritonavir or cobicistat) to enhance efficacy.
• Integrase Strand Transfer Inhibitors (INSTIs): Dolutegravir, bictegravir. Preferred first-line agents due to efficacy and tolerability.
• CCR5 Antagonists: Maraviroc, used for patients with CCR5-tropic HIV.

• Prophylaxis for Opportunistic Infections:
• Pneumocystis jirovecii Pneumonia (PCP): Prophylaxis with TMP-SMX when CD4 <200 cells/µL.
• Toxoplasmosis: TMP-SMX prophylaxis when CD4 <100 cells/µL and positive Toxoplasma IgG.
• Mycobacterium avium Complex (MAC): Prophylaxis with azithromycin or clarithromycin when CD4 <50 cells/µL.

• PCP:
• Presentation: Subacute onset of dyspnea, dry cough, fever; bilateral interstitial infiltrates on imaging.
• Treatment: High-dose TMP-SMX; corticosteroids for moderate-to-severe cases.

• Kaposi Sarcoma:
• Etiology: Associated with human herpesvirus 8 (HHV-8); more common in advanced AIDS.
• Presentation: Red or purple vascular lesions on the skin, mucosa, or organs.
• Treatment: ART with chemotherapy for extensive disease.

• Cytomegalovirus (CMV):
• Presentation: Retinitis (floaters, visual disturbances), esophagitis, colitis in immunosuppressed individuals.
• Treatment: Ganciclovir or valganciclovir; requires lifelong maintenance therapy unless CD4 recovery is achieved with ART.

• CNS Toxoplasmosis:
• Etiology: Reactivation of Toxoplasma gondii in immunosuppressed individuals.
• Presentation: Headache, confusion, seizures, with ring-enhancing lesions on brain imaging.
• Treatment: Pyrimethamine-sulfadiazine and leucovorin.

• Pre-Exposure Prophylaxis (PrEP):
• Indications: High-risk HIV-negative individuals, including MSM, injection drug users, and serodiscordant couples.
• Regimen: Tenofovir/emtricitabine (Truvada) taken daily, shown to reduce HIV acquisition risk significantly.

• Post-Exposure Prophylaxis (PEP):
• Indications: Following potential exposure (e.g., needlestick injury, unprotected sex).
• Regimen: 28-day course of ART, ideally started within 72 hours of exposure.

• Vertical Transmission Prevention:
• Management: ART during pregnancy and labor, intravenous zidovudine during labor for women with detectable viral load, and avoidance of breastfeeding in resource-rich settings.
• Infant Prophylaxis: Zidovudine for neonates exposed to HIV-positive mothers.

• HIV primarily affects CD4+ T cells, leading to immunosuppression and susceptibility to opportunistic infections.
• Diagnosis involves initial antigen/antibody combination testing with confirmatory HIV RNA or immunoassay tests.
• ART is recommended for all individuals with HIV and consists of NRTIs, NNRTIs, PIs, INSTIs, and other classes to maintain viral suppression.
• Opportunistic infection prophylaxis is guided by CD4 counts, with specific agents used to prevent PCP, Toxoplasmosis, and MAC.
• PrEP and PEP are essential strategies in HIV prevention for high-risk populations and those with recent exposure.
• Effective management during pregnancy reduces the risk of vertical transmission to infants.