HIV Flashcards
Describe the types of HIV
HIV-1
• Major cause of HIV/AIDS in U.S. and worldwide
• 3 major groups: M (main), O (outlier), N (non-M, non-O)
• Group M is responsible for the world pandemic
HIV-2
• West Africa, West India, Portugal, S. America
• Spreading into other areas
• Leads to immune deficiency, but a much slower clinical progression than HIV-1
List and describe the basic structural components of the human immunodeficiency virus (HIV)
Structure:
o Enveloped RNA human retrovirus
Components
o Pol → reverse transcriptase, protease, integrase
o Env → polypeptide cleaved to form gp120 (docking glygcoprotein) and gp41 (transmembrane)
• On viral envelope
• Needed for attachment and fusion with CD4 cells
o Gag → proteins in viral core
Describe the life cycle of HIV
o Gp120 attaches to CD4 receptor and chemokine co-receptor on host cell
o Viral envelope fuses with host cell membrane → genome released into host cell
o Reverse transcriptase copies viral RNA → DNA
• Travels to nucleus
o Integrase puts viral DNA into host genome → provirus
o Transcription and translation = polyproteins
o Viral protease cleaves into functional parts
o Assembly into nucleocapsids
o Viral particle buds from host cell = acquires their envelope and glycoproteins
Describe how HIV is transmitted.
- Sexually
- Mother to child
- Injection drug
- Contaminated blood products, tissues
- Occupational
Discuss how the virus destroys, disseminates throughout, and evades the immune system.
Replicates into innumerable quasi-species within one individual
o How? → Has compact genome (104 bp)
o RT is highly error prone (1-2/cycle)
o With high replication rate → creates diversity
Attacks CD4 T cells
o Rest of immune system falls apart
Activates the immune system
o CD4 cells active to fight back BUT only are more targets for HIV to infect
Latent reservoir = archive
o Certain long lived memory cells become infected
o The viral genome is integrated into these cells
o These cells are NOT destroyed
o Under appropriate conditions these latent cells can “wake up” and start making new viruses
o The latent reservoir is continuously replenished (Including drug-resistant variants)
• Result = can’t cure HIV
Discuss the various aspects of HIV immunopathogenesis
1) Transport from site of exposure to lymph node:
Crosses mucosal barrier
• Ex: HSV, trauma, syphilis = increase risk because disrupt barrier
Dendritic cells transport HIV to regional lymph nodes
2) Viral entry
Requires CD4 receptor and either CCR5 or CXCR4 chemokine co-receptor
If use CCR5 co-receptor = R5 tropic virus
• Most primary infection
• More prominent earlier in infection
If use CXCR4 co-receptor = X4 tropic virus
• More prominent later in infection
• Some viruses = dual-tropic
Infection of CD4+ T lymphocytes
3) Dissemination o First 4-11 days o Many rounds of viral replication in lymph nodes then dissemination o To brain, spleen, GI lymphoid tissue o Viremic but asymptomatic
4) CD4+ depletion
o First 2-3 weeks = loose ~80% CD4+ T cells
o Occurs in GI tract (major reservoir of T cells)
5) Complete immune system dysfunction → profound immune suppression
o Distorted lymphoid tissue architecture
• Decreased ability to respond to new antigens and maintain memory responses
o CD8+ T cell dysfunction (both qualitative and quantitative)
o B cell dysregulation and hypergammaglobulinemia
o NK are defective
o Neutrophil dysfunction
• Impaired opsonizing activity
• Increased rates of apoptosis
o Monocytes and macrophages = reservoirs for virus
• Infect microglial cells → CNS disease
6) Activation of immune system o Ongoing activation of immune system Humoral response: • Decline in plasma viremia to viral load “set point” due to HIV specific antibodies • Never able to neutralize due to constantly evolving genetic diversity of HIV CMI response: • Loss of CD4+ T cells • Defective CD8+ T cells
7) Latent reservoir
List the different stages of HIV infection
Primary infection:
Acute Retroviral syndrome
Chronic infection: Asymptomatic infection Symptomatic infection AIDS Elite controllers and Long-term non-progressors
Acute Retroviral syndrome
First clinical manifestation of infection
• 2-6 weeks after exposure
• Self-limited illness lasts one to several weeks
Most (50-90%) are symptomatic
• 15% are hospitalized
• Can sometimes have opportunistic infections
Commonly misdiagnosed
• Risk factors are not asked
Called a nonspecific “viral syndrome” o Fever (>90%) o Fatigue (>70-80%) – can be severe o Rash (>70%) – flat, red; Distinguishing characteristic from flu or mono o Adenopathy (40-70%) o Pharyngitis (50-70%) o Myalgia or arthralgia (54%) o Night sweats (50%) o Thrombocytopenia (45%) o Leukopenia (38%) o Diarrhea (32%) o Aseptic meningitis (25%) = This can be an important clue; when faced with a patient who has aseptic meningitis, always consider acute HIV in the differential diagnosis. o Transaminitis (20%) o Oral or genital ulcers (10-15%)
Public health threat:
• High viral plasma loads = facilitates transmission
• Most transmission from those who just acquired infection
Asymptomatic HIV infection
- Minimal or no symptoms
- Progressive immunosuppression
- Can last for years
Symptomatic HIV infection
- Fatigue/malaise
- Weight loss
- Low grade fevers and Night sweats
- Persistent generalized lymphadenopathy
Variety of dermatologic problems:
• Herpes zoster (17-fold increased risk)
• Herpes simplex (recurrent, severe)
• Skin and nail infections (persistent or recurrent)
• Seborrheic dermatitis
• Psoriasis (new, worsened, severe)
• Pruritic papules (eosinophilic folliculitis)
Oral problems:
• Thrush (white or red)
• Oral Hairy leukoplakia (from EBV)
Acquired Immunodeficiency Syndrome (AIDS)
Definition: positive HIV serologic testing and the presence of an AIDS Indicator Condition and/or a CD4 count < 200 cells/mm3
• Indicators: most are opportunistic infections (17), cancers (4) and HIV wasting
Symptoms as CD4 cell count decreases:
- Lymphadenopathy, thromboctyopenia
- Bacterial skin infections, Herpes simplex, zoster, oral, skin fungal infections
- Kaposi’s Sarcoma
- Hairy Leukoplakia, Tuberculosis
- PCP, Cryptococcosis, Toxoplasmosis
- MAC, CMV, Lymphoma
Elite controllers and long-term non-progressors
Elite controllers:
• Maintain undetectable amounts of HIV in blood without using antiretroviral drugs
• Ex: delta 32 bp deletion in CCR5 receptor → attenuated immune suppression
Long-term non-progressors:
• Ability to maintain high, well-preserved CD4 count over many years without antiretroviral drugs
Discuss the laboratory tests used to diagnose HIV and AIDS.
Standardized laboratory HIV serology:
Step 1: highly sensitive screening test = Enzyme Immunoassay
• If non-reactive → HIV-negative = no more testing
• If reactive → repeat test 2x
• If either test is reactive → perform Step 2
Step 2: highly specific confirmatory test = Western Blot
• Detects Ab’s against specific viral proteins
• Stringent criteria for positive test:
• Any 2 bands from p24, gp41, gp120/160
• If positive → HIV-positive
• If no bands detected → negative test
• If any other result → indeterminate test
Rapid HIV testing
o A screening EIA
o Takes 20-40 minutes for results
o Still need to confirm with Western Blot
Window period
o Time after infection but before HIV Ab is detectable
o Averages ~22-28 days (but can be up to 6 months)
o Result: standard serologic testing after potential exposure goes out to 6 months
Acute HIV infection
o Usually not time enough to mount detectable Ab response
• Standard serology usually negative or indeterminate
o Levels of HIV-RNA are very high = able to do a viral load PCR to diagnose
o Also able to use early viral antigen (p24) to diagnose
Distinguish acute (primary) HIV infection from acute infectious mononucleosis.
Important clues: rash, aseptic meningitis, oral or genital ulcers
Explain how HIV can be prevented.
- Access to testing and care
- Abstinence
- Risk reduction sexual practices
- Barriers
- Needle exchange programs
- Antiretroviral therapy for pregnant women and potential exposures
- Testing blood products, tissues, etc.
- Treatment = prevention
- Pre-exposure prophylaxis (PrEP)
