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Flashcards in HIV Deck (16):

Describe the types of HIV

• 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

• 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)

o Enveloped RNA human retrovirus

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
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)


Risk of opportunistic infections and malignancies based on CD4 count

Less than 200: Pneumocystis jiroveci pneumonia (PCP) = prevent with TMP/SMX

Less than 100: Toxoplasmosis (CNS abscesses) = TMP/SMX; also Cryptococcus (meningitis) and Cryptosporidosis (GI/Biliary) = no preventative tx

Less than 50: Mycobacterium avium (disseminated) = Azithromycin; also CMV and CNS lymphoma = no preventative tx