HIV Overview and Structure Quiz

HIV Structure

• HIV is a retrovirus.
• The virus has a capsid containing RNA.
• Proteins include p24 (capsid), p7 (nucleocapsid), gp41 (transmembrane glycoprotein), and gp120 (docking glycoprotein).
• The virus also has a phospholipid envelope.
• Reverse transcriptase is crucial for its replication cycle.
• Matrix protein p17
• Protease

HIV Overview

• HIV is a sexually transmitted infection (STI).
• Multiple transmission methods exist.
• HIV rapidly spread globally.
• Acquired immunodeficiency syndrome (AIDS).
• First discovered in Central Africa in 1959.
• HIV-1 group M: prevalent in the Western world.
• HIV-2: found primarily in Western Africa.

HIV Pathogenesis

• HIV attaches to human cells using CD4.
• Two chemokine receptors are involved: CCR5 and CXCR4.
• The virus replicates inside host cells, and then is released.

HIV Transmission Methods

• Sexual transmission
• Parenteral exposure to blood
• Universal precautions
• Perinatal transmission

HIV Clinical Presentation

• More common symptoms: Fever, headache, sore throat, fatigue, gastrointestinal upset (diarrhea, nausea, vomiting), weight loss, myalgia, a rash (often maculopapular and on the trunk), lymphadenopathy, night sweats
• Less common symptoms: Aseptic meningitis, oral ulcers, leukopenia
• Other observations: High viral load (may exceed 1,000,000 copies/mL or 109/L) and persistent decrease in CD4 lymphocytes

HIV Phases

• HIV infection progresses through three phases: acute, chronic, and terminal (AIDS).
• Untreated HIV infection leads to profound CD4 T-lymphocyte depletion and severe immunosuppression.
• Opportunistic infections are a major concern.

HIV Diagnosis

• ELISA (initial test)
• Western Blot (confirmation)
• Rapid HIV tests
• HIV RNA (copies/mL)
• Signal amplification nucleic acid probe
• Reverse transcriptase PCR
• Nucleic acid sequence-based amplification

HIV RNA Test Indications

• Acute infection
• Newly diagnosed
• Every 3-4 months (on or off therapy)
• 2-8 weeks after starting or changing therapy
• 3-4 months after starting therapy
• Following a clinical event or decreasing CD4 count

HIV Treatment Goals

• Reduce morbidity and mortality
• Enhance quality of life
• Preserve immune function
• Prevent further transmission

HIV Treatment Principles

• Antiretroviral therapy (ART) is recommended for everyone with HIV regardless of CD4 count.
• Factors increasing urgent ART initiation include pregnancy, AIDS-defining conditions, acute opportunistic infections, low CD4 counts (<200 cells/mm³), HIV-associated nephropathy, and acute/early infection

HIV Treatment: Drug Classes

• Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
• Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
• Protease Inhibitors (PIs)
• Integrase Strand Transfer Inhibitors (INSTIs)
• Entry Inhibitors
• CCR5 antagonists

HIV Treatment Regimens

• INSTI-based regimens (e.g., dolutegravir + tenofovir)
• NNRTI-based regimens (e.g., efavirenz)
• PI-based regimens (e.g., darunavir/ritonavir)

HIV Important Management Aspects

• Adherence
• Efficacy
• Resistance

HIV Special Populations: Pregnancy

• Dolutegravir should be avoided, if possible, Zidovudine is recommended.
• Infants born to HIV-infected mothers should receive Zidovudine or nevirapine prophylaxis for 4-6 weeks after birth.
• Breastfeeding is not recommended.

HIV Treatment Failure

• Change therapy for toxicity

• Significant virologic failure

• Immunological failure

• Resistance testing

• Prior therapy with no resistance (check adherence and address underlying causes, or start a new regimen.)

• Intensity or PK boost therapy

HIV Treatment Failure: Resistance Present

• New regimen with 2 or more active agents
• Extensive therapy with resistance (try to resuppress to prevent progression)
• New regimen with 2 active agents not possible (continue current regimen)

HIV Complications & AIDS Development

• Uncontrolled HIV leads to opportunistic infections (OIs).
• Most OIs are caused by environmental organisms.
• OI development is linked to CD4 count.

HIV and AIDS: Specific OIs

• Pneumocystis pneumonia (PCP): Primary prophylaxis in patients with CD4 < 200/mm³.
• Cryptococcal meningitis: Primary prophylaxis – not indicated
• Cytomegalovirus retinitis: Primary prophylaxis with CD4 < 50/mm³, regular retinal examinations.
• Mycobacterium avium complex (MAC): Primary prophylaxis with CD4 < 50/mm³. Clarithromycin or azithromycin, or rifabutin treatment.
• Toxoplasmosis: Primary prophylaxis with CD4 ≤ 100/mm³. TMP/SMX or dapsone/pyrimethamine.