ICL 1.15: AIDS Flashcards

(74 cards)

1
Q

which family of viruses is lentivirus in?

A

retrovirus

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2
Q

which cells does HIV infect?

A

infects T-cells and macrophages primarily

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3
Q

what receptors does HIV have to bind to to succesfully enter a cell?

A

must bind to CD4 receptor

AND

B-chemokine co-receptor is needed for viral entry

CCR5 or CXCR4 are major co-receptors

so you need both CD4 and either CCR5 or CSCR4 for HIV to bind to host cell

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4
Q

what is the root cause of clinical manifestations of HIV?

A

loss of the T-cell arm of the immune system results in the clinical manifestations of HIV

occurs through the decline of CD4 cells

but the mechanism of decline is only partly understood

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5
Q

how many types of HIV are there?

A

HIV comes in 2 types: HIV1 and HIV2

HIV2 isn’t common in the US

HIV1 comes in different groups: M,N,O,P

then in HIV1M there are different subtypes/clades: A-K

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6
Q

what is the prevalence of HIV in the US?

A

HIV prevalence is increasing due to derease in death rate

HIV incidence is decreasing due to anti-viral therapy

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7
Q

transmission of a virus depends on which 3 major factors?

A
  1. inoculum dose
  2. exposure time
  3. host susceptibility

you need all 3 things to get an active infection

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8
Q

which body fluids are not HIV infectious?

A

non-bloody fluids such as saliva, tears, sweat, feces are non-infectious

saliva has antibody, not virus

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9
Q

which body fluids are HIV infectious?

A
  • blood
  • genital fluids
  • cerebrospinal fluid
  • breast milk
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10
Q

what is the inoculum dose?

A

the amount of virus required to set up an active infection

some viruses have very low inoculation doses which is scary because it means it doesn’t take alot of the virus to infect someone

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11
Q

what is the viral load?

A

the amount of virus

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12
Q

how does HIV host-susceptibility work?

A

host susceptibility requires TWO receptors to get into the cell

if you lack one of the receptors like CD4 or one of the coreceptors (CCR5 or CSCR4) it decreases your susceptibility to HIV

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13
Q

what is the most common exposure route of HIV?

A

blood transfusion

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14
Q

how are we trying to eliminate HIV?

A

by decreasing the viral load in a person to the point that it’s almost zero

if the viral load is undetectable then you can’t transmit it to another person during sexual contact!

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15
Q

what are the characteristics of an acute HIV infection?

A

it’s usually self-limiting!

onset of illness is about 2 weeks after infection

and you start making antibodies a couple weeks in

most patients don’t present for medical care during acute HIV infection

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16
Q

what are some of the symptoms of HIV?

A
  • fever
  • fatigue
  • myalagia
  • skin rash
  • headache
  • pharyngitis

these are all pretty vague so most people don’t go to the doctor in the early stages of HIV

it also often gets mistaken as mononucleiosis

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17
Q

what are the differences between HIV and EBV?

A

HIV
- acute onset

  • minor tonsil tissue hypertrophy and exudate is rare
  • mucocutaneous ulcers common (35-50%)

= rash common (<50%)

EBV
- subacute onset

  • significant tonsil tissue hypertrophy and exudate is common
  • mucocutaneous ulcers are rare
    rash is rare without penicillin/amoxicillin use
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18
Q

what does an HIV rash look like?

A

literally nothing

it’s so faint and doesn’t last long either

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19
Q

how does your CD4 count change throuhghout an HIV infection?

A

when you get infected with HIV there’s disregulation and deterioration of T cell arm of the immune system

usually a healthy person has 1000 cells/cc CD4 cells

with infection your CD4 cell count takes a sharp drop then recovers quickly then declines over the years

but you don’t get sick till your CD4 count is less than 200 and you’ll be super sick when it’s under 50

the problem is that when someone comes into your office with vague symptoms and their CD4 count is still pretty normal, it’s hard to figure out what’s wrong

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20
Q

what’s the range of CD4 cells throughout an HIV infection?

A

CD4 Count > 500 (28%) often asymptomatic

CD4 Count 200 - 500 increasing incidence of thrush, shingles, pneumococcal pneumonia, etc.

CD4 Count <200 (14%) at risk for opportunistic infections. Begin PCP prophylaxis. AIDS by CDC definition

CD4 Count <50 at risk for Mycobacterium avium infection, cytomegalovirus

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21
Q

when will HIV patients present to the clinic?

A
  1. Patients are more likely to present with protean clinical complaints that point to a damaged immune
    system= CD4 < 200
  2. Or self-refer for testing because they perceive themselves to be at risk
  3. Or present with an AIDS –defining illness
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22
Q

what are the clinical findings that suggest HIV?

A
  1. persistent generalized lymphadenopathy
  2. unexplained cytopenia (RBC, WBC, PLT)
  3. recurrent pneumonia
  4. Kaposi’s sarcoma
  5. trush (oral candidiasis)
  6. wasting syndrome
  7. TB
  8. pregnancy (all pregnant women need HIV test during each pregnancy)
  9. STD/STI
  10. CNS involvement like depression, memory loss, neuropathy
  11. fever of unknown origin
  12. unexplained constitutional complaints
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23
Q

what diagnotic tests can you run at the different stages of HIV?

A

post infection:

1 week: viral RNA

2 weeks: p24ag

5 weeks: western blot

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24
Q

how do you diagnose HIV?

A

HIV is diagnosed by detection of viral RNA, p24antigen, or antibody

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25
what is a 3rd generation HIV test?
3rd generation HIV tests detect IgG/IgM AB to HIV 1 and HIV 2 but this must be confirmed with a western blot
26
what is a 4th generation HIV test?
4th generation HIV tests detect IgG/IgM AB to HIV 1 and HIV 2 and p24 Ag but this must be confirmed with a differentiation assay
27
what is the eclipse period?
the eclipse period is the initial interval after HIV infection when no existing diagnostic test is capable of detecting
28
would you rather have a low or high viral load with a low or high CD4 count?
you'd rather have a low CD4 count with a low viral load because the infection will more slower
29
what is the goal of antiretrovirals?
to obtain an undetectable viral load they can restore NORMAL life expectancy and decrease morbidity and viral transmission
30
what are the 5 FDA approved drug classes for HIV treatment?
1. NRTI 2. NNRTI 3. PI 4. Entry inhibitors - Fusion inhibitors - Chemokine receptor inhibitors 5. Integrase inhibitors
31
how do NRTIs work?
NRTI = nucleoside reverse transcriptase inhibitor it works at the level of nuclear viral replication to inhibit HIV
32
which drugs are NRTIs?
1. AZT 2. lamivudine 3. tenofovir 4. abacavir, 5. emtricitabine lamivudine, emtricitabine, and tenofovir are active against hepatitis B 
33
what is a side effect of AZT?
AZT = zidovudine; it's an NRTI macrocytic anemia!
34
what is a major complication with abacavir?
it's an NRTI and a hypersensitivity reaction can occur if the patient is HLA B5701+ hypersensitivity reaction is characterized by fever, rash, elevated LFTs, GI upset and/or respiratory symptoms avacavir can be fatal on rechallenge if you give the patient the drug again... so we have to screen for this with HLA B5701and do not give to HLA B5701+ patients
35
how do NNRTIs work?
NNRTI = non-nucleoside reverse transcriptase inhibitor they work at enzymatic level and binds to the reverse transcriptase enzyme disrupting the catalytic site and prevent HIV
36
which drugs are NNRTIs?
1. nevirapine 2. efavirenz 3. etravirine 4. rilpivirine 5. doravirine
37
how do protease inhibitors work?
protease inhibitors inhibit HIV protease enzymes which disrupts the cleavage and packaging of the HIV virus they're often given with ritonavir or cobicistat as a booster **sidenote: all PIs can cause acute onset of diabetes and significant hypertriglyceridemia
38
which drugs are protease inhibitors?
1. darunavir | 2. atazanavir
39
what are the side effects of ritonavir?
NVD
40
what are the side effects of indinavir?
1. hyperbilirubinemia | 2. kidney stones
41
what are the side effects of nelfinavir?
diarrhea
42
how do entry inhibitors work?
drugs which prevent HIV entry into CD4 cells
43
which drugs are entry inhibitors for HIV?
1. fuseon 2. maraviroc 3. ibalizumab
44
how does fuseon work?
it's an entry inhibitor it binds to gp41 to prevent virus fusing with the cell membrane
45
how does maraviroc work?
it's an HIV entry inhibitor it is a CCR5 coreceptor antagonist Berlin patient (only person cured of HIV) received a BM transplant from a CCR5 (-) donor
46
how does ibalizumab work?
HIV entry inhibitor binds to CD4 receptor
47
how do integrase inhibitors work?
they prevent integration of viral DNA into the host genome
48
which drugs are integrase inhibitors?
1. Raltegravir 2. Elvitegravir 3. Dolutegravir 4. Bictegravir 5. Cagotegravir
49
when do you start ART?
ART = antiretrovirals (used to treat HIV) you always start ART immediately!! even if the patient is pregnant
50
what is AIDS?
AIDS is a clinical syndrome characterized by severe immune suppression there are 23 clinical illnesses seen in the presence of HIV infection or a CD4 count less than 200 meet the clinical definition of AIDS by the CDC
51
what does IRIS stand for?
IRIS = immune reconstitution inflammatory syndrome it can occur when ART is started with AIDS
52
what are some of the AIDS defining illnesses?
1. CMV 2. MAC = mycobacterium avium complex 3. PCP = pneumocystis carinii pneumonia 4. toxoplasmosis 5. cryptococcosis 6. cryptosporidia 7. candida esophagitis 8. PML
53
when do HIV patients get CMV? what symptoms does it cause?
it's an AIDS defining illnesses risk for CMV infection greatest at CD4 < 50
54
what symptoms does CMV cause when it's an AIDS defining illness?
1. chorioretinitis = decreased vision, floaters, visual field defects 2. colitis = diarrhea, wt loss, fever, abdominal pain 3. esophagitis = dysphagia, dyspepsia, odynophagia 4. rarely causes pneumonia
55
how do you treat CMV when it's an AIDS defining illness?
1. ganciclovir 2. foscarnet 3. cidefovir
56
what is the most common systemic bacterial infection in AIDS patients?
MAC = mycobacterium avium complex
57
when do AIDS patients usually get MAC infections?
CD4<50, almost always <100
58
what are the symptoms of MAC when it's an AIDS defining illness?
fever night sweats weight loss +/- diarrhea
59
how do you diagnose MAC?
diagnosis by culture - blood, bone marrow, liver, stool
60
how do you treat MAC when it's an AIDS defining illness?
macrolide + ethambutol + fluoroquinolone + aminoglycoside often used in acutely ill patients, with discontinuation of aminoglycoside as outpatient pretty complicated...
61
when are AIDS patients susceptible to PCP?
PCP = pneumocystis carinii pneumonia CD4 < 200
62
what are the symptoms of PCP when its an AIDS defining illness?
1. gradual increase of dyspnea on exertion 2. fever 3. dry cough 4. weight loss 5. interstitial infiltrates on CXR
63
how do you treat PCP when it's an AID defining illness?
trim sulfa:15 -20 mg/kg q6-8 hours x 3 weeks Atovaquone for mild-moderate PCP
64
what is the most common cause of focal encephalitis in AIDS patients
toxoplasmosis happens when CD4<200
65
what are the symptoms of toxoplasmosis when it's an AIDS defining illness?
focal neurologic deficits seen including weakness, seizures, confusion, coma CSF often unremarkable if obtained **CT with ring -enhancing lesion
66
how do you treat toxoplasmosis?
pyrimethamine +sulfadiazine + leukovorin
67
which disease is a commo cause of chronic meningitis in AIDS patients?
cryptococcosis
68
what are the symptoms of cryptococcosis?
subacute presentation with headache, fever, malaise 90% of patients with cryptococcosis have associated meningitis
69
which factors are poor prognostic factors for meningitis?
1. <20 WBCs in CSF 2. increased ICP 3. impaired mental status 4. CSF ag titer of >1;1054
70
what is cryptosporidia?
parasitic cause of diarrhea in 10-20% of AIDS patients N/V, wt loss, RUQ pain, and a predilection for biliary tree involvement diagnosis by AFB stain of stool very difficult to treat paromomycin or azithromycin
71
which symptoms does candida esophagitis cause?
often see dysphagia and retrosternal pain on swallowing
72
what is PML?
PML = Progressive multifocal leukoencephalopathy caused by polyomavirus JC unlike the AIDS global dementia, PML symptoms tend to progress rapidly and focal changes are often seen including ataxia, hemiparesis, and speech difficulties
73
how do you diagnose PML?
Dx is by MRI
74
what is the treatment for PML?
TX is to raise the CD4 count and reverse the immunosuppression