IID: HIV/AIDS 1-3 Flashcards
What is p24 (Gag) antigen in blood a marker of?
HIV
What are some main opportunistic infections/pathogens assoc with HIV/AIDS?
Kaposi’s sarcoma
PCP
Candida
Another hallmark of HIV/AIDS (cell count)
LOW WBC COUNT!
What is the defining feature of a retrovirus and what can it do?
RT, which can convert RNA to DNA
Which viruses (and genus) cause AIDS?
HIV1/2, in the Lentivirus family
What do simple retroviral gag pol and env encode? (genes)
gag-core viral prot pol-RT env-envelope prots -LTRs control prot expr (long tandem repeats on virus) -complex retrovirus has more genes
What are some genes in oncogenic viruses
v-rel: allows for modification of host chrom, causing malig
src: encoded by some viruses and causes cancer (cell signaling pathways) (eg in RSV, rous sarcoma virus)
Human-T-cell leukemia virus (HTLV-1)
-complex virus with icosahedral core, doesnt actually contain an oncogene but DOES cause cancer esp adult t-cell leuk/lymphoma (ATLL) (so carriers of this virus have a lil chance of getting ATLL)
ATLL: affects CD4+ cells, asia/africa/carib middle aged
IV drug users
no vaccines (***non HIV retroviruses are lower yield)
MMTV
mouse mammilary tumor virus
complex retrovirus w vertical germline parent to child transmission or hz thru breastmilk (sometimes HMTV found in ppl w BC)
Why does HIV often lead to cancers?
bc of immunsuppression, so pt cannot conduct normal tumor survellience
Where is it thought that HIV-1 originated
bush meat (monkeys, from SIVcpz)
HIV-1 virus description (env)
most widespread HIV strain
ENVELOPED retrovirus in the LENTIVIRUS family (env has glycoprots to attach to host cells)
Viral RNA enclosed in capsid
What ENZYMES does HIV-1 virus contain
- RT (makes dna copy of viral rna genome)
- integrase (integrates dna copy of viral genome into host dna, so viral mRNA and prot can be produced)
- protease: processes precursors to viral proteins
What cells does HIV mainly affect?
CD4+ T-cells! (weakens immune sys, and overtime can cause AIDS)
Why is not everyone who comes in contact with HIV affected by the virus?
not that stable, bc attachment prot gp120 is shed fast
-since enveloped, sensitive to heat drying etc
what bodily fluid is HIV NOT transmitted thru
NOT transmitted thru saliva (has proteases that inactivate virus)/tears/sweat
How does a retrovirus attach?
CD4, gp120, gp41
virus attaches to CD4 on host cell via gp120 on its own envelope (CD4 is on T cells macros and microglia in brain, causing CNS sx). after binding, coreceptors cause gp41 to be rel from virus, which inserts into host cell memb and holds them together so membrane fusion can occur
RETROVIRAL ENTRY AND REPLICATION
Once virus enters cytoplasm, it uncoats.
Each RNA copy (2 per virion) produces a double stranded DNA copy of the RNA via RT. (i.e., goes from viral RNA to DNA).
Then this DNA is integrated into host DNA via enzyme integrase.
Then this viral DNA is transcribed into mRNA and translated into protein (the regular way)
-Then new viral particles are asembled and released from cell as immature (noninf) particles, and protease matures them to be infectious.
HIV/AIDS clinical course if untreated:
Patient infected by virus, increases viral RNA, and decreases CD4+ cells (primary infection).
Then during clinical latency, immune sys kicks in, decreases HIV RNA in blood and slightly incr T-cells.
Virus wins out, and CD4+ drops drastically (viral load incr).–this means pt has AIDS (high risk for opp infxns)
HIV/AIDS clinical course if treated with HAART (anti-retroviral tx)
Same primary stage
Drive RNA viral load very low, and can maintain CD4+ to only SLIGHTLY lower than normal
Can have relatively normal lifespan!
What diseases is characterized by consistently low CD4+ T-cell count?
AIDS (almost always found in ppl infected with HIV virus, has ab’s against HIV)
High vs low levels of HIV viruses predicts?
HAART predicts?
high vs low risk of dev AIDS
w/ HAART, low risk of dev AIDS bc low viral load
(children born to HIV infected mothers can also get AIDS)
-HIV being cause of AIDS follows Kochs postulates (criteria for det whether certain factor causes disease)
How does HIV kill CD4+ cells?
lots of ways, incl necr/apop, fusion, G2 cell cycle blockade, TAT EFFECTS (tat is prot encoded by HIV-1 that increases viral transcription), rel to affect bystander cells
Dropping CD4+ count causes AIDS
4 opportunistic infections seen mostly in AIDS
PCP (pneumonia), have drugs now, crushed ping pong ball histo
Mycobacterium avium
Candida
HHV-8 (Human Herpes Virus 8) which causes Kaposi’s sarcoma
Which virus causes Kaposi’s sarcoma?
HHV-8
Commonly used tests for HIV infection, and window periods?
ELISA immunoassay- 16-25d
oral rapid
western blot 25d
flow cytometry (checks CD4+ count but not HIV necessarily)
NAT (nucleic acid test) measures viral load, 12d
Genotyping to detect viral mut that result in resistance to HAART
(shortest seems like NAT?)
How specific and sensitive is current HIV testing?
> 99%!
but false positives can occur with SLE, ab’s to other infections etc
Some examples of HIV treatments, and how they can affect certain steps in HIV infectious process
Fusion inhibitors prevent viral attachment
RT inhibs prevent HIV RNA from being conv to DNA to be int into host genome
INtegrase inhibs prevent integration of viral DNA from RT into host
Tat antagonists can decr HIV transcription from Tat so decr amount of virus particles transcribed to be rel
Protease inhibs can decr amount of active/mature viruses that have been released
Why is there no vaccine for HIV?
HIV is enveloped w glycosylated glycoprots that arent good epitopes
Virus mutates quickly to avoid immune resp
Thousands of strains
Does HIV encode an oncogene?
NO!!!
but some other retroviruses do
Screening recommendations for HIV
screen adults age 15-65 (and outside this range if at incr risk), for v high risk can screen anually (eg MSM, IVDU, sex workers, unprotected sex, all pregnant women)
-ART can also prevent transmission to other ppl bc decr viral load
What disease states incr urgency for ART use?
HIV assoc conditions (malig, dementia, nephro) OIs lower cd4+ count co-inf with HBV or HCV acute/early infxn
Types of current ART meds?
RT inhibs (nucleoside aka NRTIs and non-nucleoside)
Protease inhibs
Integrase inhibs
(recommend 2 NRTIs + smth else)
Predictors of inadequate adherence to HAART
regimen complexity literacy/pt educ drug/alc use mental health issues sxe and fatigue
HAART how often to check CD4+ and Viral load count
check viral load count more often
viral load decr a lot (want to get to <200), and CD4+ incr gradually
Leading cause of OI (opportunistic infection) death globally?
TB!!!
isoniazid + rifa
How to prophylatically treat OIs with CD4 counts of: -any <200 /thrush/OI history <100 <50
-any: treat TB
<200 treat for PCP, TMP-SMX DS daily
<100 treat for toxoplasmosis: only if toxo igG+, same tx as above
<50 treat for MAC with azithro, (CMV retinitis may occur but no prophylaxis indicated), screen for cryptoccoccal meningitis
What diseases should you vaccinate for in ALL pts with HIV/AIDS>
Pneumococcus
Influenza injxn
Tetanus/ Dipth/ pertussis (TDaP)
Meningococcus
(SOME may want HAV, HiB, HPV, MMR, Varicella dep on CD4+ count)
What is IRIS (iimmune reconstitution syndrome)
worsening of preexisting dis after init of HAART, usu just in first few weeks tho
who should receive ART?
all indivs with detectable HIV load, regardless of CD4+ count
What type of vaccine should AIDS/HIV pts NOT receive?
live attenuated, bc theyre immunocompromised!
eg dont give HIV pts shingle vaccine bc live!
at less than 500 CD4+ in HIV, what infx is most likely to occur?
TB! and others
At less than 200 in AIDS, what infxn likely to occur
CANDIDA ESOPH
PCP
and others
What opportunistic infections are likely to occur at less than 100 and less than 50 in HIV?
MAC
CMV
AIDS defining is CD4+ count of less than…
200!
how long is HIV avg latency
LONG! 10 yr avg
Toxoplasma encephalitis cx
MULTIFOCAL brain lesions, multiple ring enhancing lesions in periventricular WM of basal ganglia
Toxoplasma gondii
sx
cd4 count?
dx
protozoan with cats that eat it and poop it out, other animals eat it
sx tissue cysts
CD4<100
dx if MRI lesions, HIV, toxo IgG ab’s, treat pt
HHV-8/Kaposi’s sarcoma
CD4 count
GREATER than 200!!!
What does kaposi’s sarcoma come from
HHV-8 after HIV
Kaposis sarcoma sx
Dont confuse w
Tx
histo
lesions on skin etc, eleph
dont confuse w bartonella
Tx w. chemo
histo: spindle cells on slides
who is at risk for cryptococcus neoformans based on CD
those w CD<100 (profound immunnosupp)
Other sx of cryptoccocus
high intracranial pressure
CSF may look normal
skin lesions
for cryptococc u take latex aggl of where?
CSF (brain and spine)
what is oft absent in cryptococc in HIV
classic meningeal signs
PCP at what cd4 count?
<200, or less than 14%, use PROPYLACTIC treatmeant for OIs!
check for toxoplasma if gets to below 100
what cells does pcp attach to
alveolar and fills them with foamy eosin exudate
other pcp sx
what is elev
dry cough (non prod) LDH elev! and B-glucan
Primary prophylaxis for OIs (CD levels) in HIV
at less tha 200, uses PCP prophylaxis tx
at less than 100, uses toxoplasma prophylaxis
at less than 50, use MAC prophylaxis
Case studies: HIV pts with
1) seizure, motor issue, ring enhancing lesions
2) CD over 200 (and 500), major skin lesions
3) no meningeal signs but has headache, v high intracranial pressure
4) dry cough, HIV+
1) toxoplasmosis
2) kaposis sarcoma
3) cryptococcus neoformans
4) PCP
What is a main sx in kaposi’s sarcoma
SKIN LESIONS!
