HIV Flashcards
HIV modes of transmission.
- Directly by bloodstream
- Through abraded mucosa (sexual)
- Through genital secretions (semen)
Which cells does HIV infect? Where?
CD4+ cells (Th cells)
Monocytes and macrophages
Virions migrate to lymph nodes and infect local CD4+ cells, as well as those circulating through. Eventually these (and the virus) reach the bloodstream.
3 stages of HIV and time frames for each.
- Burst of viral replication. 2-6 weeks after infection. Sx last 2-4 weeks.
- Asymptomatic period. Steady-state level of virus reached after 6-9 months. May last years.
- AIDS. Average time between infection and AIDS is 10-11 years.
Symptoms of 3 stages of HIV.
- Fever, sore throat, malaise, rash, lymphadenopathy, h/a, myalgia.
- No symptoms in asymptomatic period.
- Various opportunistic infections in AIDS period. 90% cases result in death.
List common opportunistic infections/diseases that HIV patients are subject to.
- Pneumocystis carinii
- Cytomegalovirus (CMV)
- Cryptococcus
- Mycobacteria
- Toxoplasma
- Kaposi sarcoma
- Chronic lymphadenopathy
- Rare lymphomas
Describe the mechanism by which HIV replicated in Th cells, including enzymes.
HIV attaches using gp120 to CD4 (CXCR4 also necessary). Viral envelope fuses and 2 RNA strands enter host. Reverse transcriptase transcribes RNA to ssDNA. RNAse H destroys viral RNA. Polymerase makes dsDNA, which integrase inserts into host genome. Activation of host cell causes viral DNA to transcribe into viral RNA and synthesize new viral particles.
Describe 2 ways macrophages/monocytes can be infected by HIV.
- Engulfment of free HIV or HIV attached to Ab.
- Attachment of gp120 to CD4.
List 3 ways cell death can occur during HIV.
- Complement activation causes lysis. Due to Ab to gp120 and gp41 on infected cell.
- ADCC—Ab dependent cell mediated cytotoxicity. Monocytes/macrophages attach to Fc of Ab on infected cells.
- Cytotoxic T-cells are directed to viral proteins on surface of infected cell.
How can CD4+ depletion occur during HIV…even noninfected cells?
Possible reasons:
- HIV may kill/infect/impair cells that are necessary for growth of CD4+ lymphocytes.
- HIV may induce cells to secrete substances that are toxic to CD4+ lymphocytes.
- gp120 on surface of infected cells may react with CD4, leading to fusion and giant multinucleated cells that die.
- Free gp120 binds to CD4 leading to production of Ab against these cells (autoimmunity).
How does HIV infection impair the function of CD4+ cells?
- gp120 binding to CD4 prevents the interaction of the T-cell with MHCII.
- infected cells cannot express CD4, and do not produce as much IL-2, which activates cytotoxic T-cells.
How are the cytopathic effects of HIV on monocytes/macrophages different from those on Th cells?
Cytopathic effect is much less significant for monos/macros because they have less CD4. They may act as a reservoir for HIV, transporting it throughout the body.
List screening, confirmatory, and monitoring tests used for HIV. (8 total)
Screening:
- Rapid HIV-1/2 Ag/Ab Combo (Alere)
- HIV-1/2 Ag/Ab Combo immunoassay
Confirmatory:
- HIV-1 Western blot
- HIV-1/2 Ab differentiation immunoassay
- HIV-RNA Qualitative test
Monitoring:
- HIV-RNA Quantitative test (Viral load testing)
- HIV genotyping
- CD4 counts and CD4:CD8 ratio
What are the specimen requirements for an HIV-RNA test?
Best to keep sample completely sterile (ie don’t use it for another test before hand).
EDTA and ACD whole blood must be frozen and plasma removed within 6 hours of collection to prevent degradation of RNA by native RNases in plasma.
Different assays of HIV-RNA quantitation will yield different results, so the kit used should be consistent.
What does the CD4:CD8 ratio tell use about the course of HIV infection?
What is a normal ratio?
Normal is greater than 1.
The ratio tells us about the progression of AIDS. Low ratio is a late manifestation of AIDS.
What is the goal of antiretroviral therapy in HIV patients?
Complete, maximal, sustained, uninterrupted inhibition of virus replication, resulting in the decrease of HIV-RNA levels and increase of CD4+ cell count.
Describe the action of antiretroviral drugs.
Inhibit either reverse transcriptase or the proteases necessary for viral replication.
Which test is most useful in monitoring the effectiveness of antiretroviral drugs?
Viral load (HIV-RNA quantitative)
What does HAART stand for and what effect should it have on an HIV patient?
Highly Active AntiRetroviral Therapy
Should result in substantial decline in viral load by 4-8 weeks, and lead to viral loads < 500 copies/mL in 12-16 weeks.
Risks/limitations of antiretroviral therapy for HIV.
- Side effects
- Duration of effectiveness unknown
- Replication of virus not completely stopped
- Therapy cannot be withdrawn
- Eventual breakthrough of resistant virus seems inevitable
HIV discovered when?
1981
2 HIV strains have about —% homology
50%
HIV DNA intermediate is integrated into host cell genome as a(n) ——-
provirus
Seroconversion occurs when in HIV infection?
First stage (2-6 weeks)
About —-% of AIDS patients develop CNS & PNS disease
35%
RNA –> DNA
reverse transcriptase
HIV cytopathicity highest in cells with…
highest CD4 density
Explain the T-cell event that leads from the latent period to AIDS
Mitogens or antigens stimulate T-cells, leading to their activation, resulting in cytokine production and extensive viral replication.
During HIV’s latent period, viral load (stays steady/increases/decreases) and CD4 count (stays steady/increases/decreases).
viral load stays steady
CD4 count decreases (gradually)
1st and 2nd generation HIV testing detected —— and took —— days to be detectable
HIV-1 Ab only
42-60 days
3rd generation HIV testing detected ——- and took —— days to be detectable
HIV-1/2 Ab
21-24 days
4th generation HIV testing detects ——- and takes ——- days to be detectable
HIV-1/2 Ab and p24 Ag
14-15 days
earliest routine marker for HIV detection
p24
p24 is positive within —– weeks of exposure
2-3
p24 detection is problematic in which pop?
children < 1 month
p24 marker disappears once…
Ab is present. Reappears in AIDS.
HIV-1/2 Ab appears within what time after exposure? Average?
6 weeks to 6 months. Average is 2 months.
2 main methods of HIV-1/2 Ag/Ab combo assay
CLIA
ELISA
When is the rapid HIV combo test done now?
Employee exposure incidents.
Pregnant women with unknown HIV status at time of delivery.
3 types of HIV viral proteins detected by Western blot
GAG (group specific antigen)
POL (polymerase)
ENV (envelope)
Explain HIV Western blot results.
At least 2 major bands is considered positive.
Only 1 major band is considered indeterminate. Repeat in duplicate.
No bands must be present to be considered negative.
Faster, fewer indeterminates, and less expensive than Western blot for HIV.
HIV-1/2 Ab differentiation immunoassay.
HIV-RNA detects RNA —- days after infection
10-12
FDA approved methods for HIV-RNA
PCR
TMA (transcription-mediated amplification)
CDC recommends which step if a patient tests negative for HIV-1 and HIV-2 on the Ab differentiation test?
HIV NAT test
Minimum “goal” CD4 cell count
500 cells/nL^3
HIV-RNA quantitative tests detect down to —- copies/mL
20
Valuable prognostic indicator for HIV during latent phase.
Viral load.
< 5000 copies/mL indicates low rate of progression.
> 50,000 copies/mL indicates high rate of progression.
Test that would be done if HIV viral load suddenly increases during treatment.
Genotyping
Genotyping has limited usefulness when patient’s HIV levels are less than —–
1000 copies/mL
CD4 count indicating AIDS
< 400 cells/nL^3
CD4 count indicating great risk for opp. infection
< 250 cells/nL^3
CD4 count indicating great risk for P. carinii
< 200 cells/nL^3
HIV can get stuck on the surfaces of —— cells
dendritic
Viral load monitoring for AIDS patients happens every —- months
3-4
