Flashcards in HIVInfections Deck (50):
When was AIDS recognized as clinically distinct illness?
1981 (due to increased cases of Kaposis sarcoma and PCC)
Peak of death due to HIV disease in US:
Features of HIV Virion:
Envelope > Matrix > Nucleocapsid > Genome
Attachment protein for HIV:
**Fusion protein for HIV:
Reverse Transcriptase for HIV:
HIV carries pol gene > encodes for reverse transcriptase
**Matrix protein for HIV:
**Capsid protein for HIV:
Life Cycle of HIV: Attachment:
gp120 binds to CD4 > conformational change in gp120 to allow binding to a CORECEPTOR (ABSOLUTELY NECESSARY)
Coreceptors for HIV:
Uses CCR5 as co-receptor, Predominant EARLY in disease
Uses CXCR4 as a coreceptor, 40% of patients transition from R5 to X4 > rapid progression to AIDS
Deletion to CCR5 Gene:
affects its binding to gp120
Heterozygous Deletion of CCR5 gene:
longer asymptomatic period before onset of AIDS
Homozygous deletion of CCR5 gene:
NO infection with R5-tropic viruses. X4-TROPIC CAN INFECT.
HIV Life Cycle: Fusion:
gp41 mediates fusion between the viral envelope and plasma membrane
HIV Life Cycle: Reverse Transcription:
pol gene found within virus > reverse transcriptase, produces a linear dsDNA copy of HIV genome
What allows for rapid evolution of HIV during course of disease?
The high error rate of its reverse transcriptase. It it the MOST error prone of all retroviruses.
HIV Life Cycle: Integration:
dsDNA into nucleus > VIRAL INTEGRASE causes dsDNA to be incorporated into host DNA > PROVIRUS > Provirus is transcribed
HIV Life Cycle: Egress:
Progeny HIV Virions EXIT the infected cell by BUDDING through the plasma membrane at LIPID RAFTS
HIV Life Cycle: Maturation:
Protease cleavage of gag and gag-pol polyproteins > ESSENTIAL FOR INFECTIVITY
Immature vs Mature Virions
Light and homogenous = immature. Darker with dark nucleocapsid center= mature.
Overall transmission risk of HIV from mother to child:
Highest risk of transmission of HIV from mother to child occurs when:
at birth (50-65%)
Risk of HIV transmission due to skin puncture from a needle:
Risk of transmission due to mucous membrane exposure:
HIV Progression: Acute HIV Syndrome
3-6 weeks following infection. Burst of Viremia (p24/RNA) Anti-HIV antibodies may not be detectable
HIV Progression: Acute HIV Syndrome Symptoms:
Similar to infectious mono with a rash.
Following the initial burst of viremia with acute HIV syndrome, what happens to virus levels in the blood:
They decrease due to mounted immune response (anti-HIV antibodies appear)
HIV Progression: Chronic Phase:
Low level viremia? Patients often asymptomatic. Untreated patients = can persist for 10 years.
HIV escape from immune system during chronic phase of infection:
Antigenic drift of gp120, Inactivation of key elements of immune response, Cell-to-cell fusion (passed without going into EC area)
*HIV-Associated Infections (6):
Oral Hairy Leukoplakia (EBV), Pneumonia (PCC, TB), Candida Albicans (Thrush), CMV retinitis, Neoplasms (KS), Diarrhea
HIV Virus Family:
Serology during Acute HIV Infection:
High levels of HIV RNA and p24 (p24 will drop off but RNA persists as infection progresses)
Progression of things detectable with HIV infection:
HIV RNA detectable by NAAT > p24 > Abs
First screening test for HIV:
Testing for ANTIGEN (p24) AND ANTIBODY to HIV-1/2
Following a HIV screening test, what is the next diagnostic step?
HIV-1/HIV-2 ANTIBODY differentiation Immunoassay
Final step of HIV Diagnosis if immunoassay shows HIV- 1 (-) and HIV-2 (-):
HIV-1 nucleic acid test to detect HIV RNA genome
Two classes of Entry Inhibitors and indication for use:
Chemokine coreceptor antagonists, Fusion inhibitors, NOT indicated for treatment of NEWLY diagnosed patients.
*MOA + Limitation of Chemokine Receptor Antagonists:
Binds to co-receptor and prevent its interaction with gp120 *(limited to R5-tropic)
MOA of Fusion Inhibitors:
Bind to gp41 and prevent conformational change needed for fusion
Two varieties of Reverse Transcriptase Inhibitors:
Nucleoside inhibitors (NRTIs), Nonnucleoside Inhibitors (NNRTIs)
*Method of action of NRTIs:
Incorporated into growing dsDNA chain and this leads to failure of chain to be integrated into host DNA.
*MOA of NNRTIs:
bind to reverse transcriptase and inhibit its activity.
Integrase Inhibitor MOA:
blocks integration of the DNA viral copy into the host DNA
Protease inhibitor MOA:
Inhibit protease cleavage > production of IMMATURE, DEFECTIVE HIV particles
Preferred Combination ARV Therapies for initial therapy:
1 NNRTI + 2 NRTIs, 1 PI + 2 NRTIs, 1 II + 2 NRTIs (2 NRTIs for EACH)
3 ways to reduce mother to infant spread:
Antiviral treatment of mother and child. Refrain from breast feeding. C-section delivery