HIV

Question 1

gp41, HIV

Answer 1

transmembrane protein(hookshot)
associates with gp120 on envelope surface

Question 2

p17, HIV

Answer 2

matrix proteins

Question 3

p24, HIV

Answer 3

capsid proteins

Question 4

p7, HIV

Answer 4

nucleocapsid proteins

Question 5

transmission of HIV

Answer 5

mucosal: sex or mother»child @birth
parenteral: direct injection

Question 6

how does HIV invade the body when it goes the mucosal route?

Answer 6

• DCs trap HIV and pass to/infect CD4+ Tcells
• Breach in endothelium
• Transcytosis

Question 7

describe HIV cell surface interactions when infecting a cell

Answer 7

gp120 binds CD4

gp120 transforms and binds CCR5 or CXCR4

gp41 is exposed and extends to target cell, initiating fusion

Question 8

tRNA lysine role in HIV infection

Answer 8

primer for RT

Question 9

structural genes for HIV

Answer 9

gag, pol, env

gag and pol code polyproteins that are cleaved into respective structural proteins after translation

Question 10

trans-activator genes?

what do they do?

Answer 10

tat and rev

tat - essential for HIV transcription; binds tat-activation region on all species; activates cellular promoters

rev - essentially binds and chaperones RNA out of the nucleus that hasnt been spliced(or just single spliced) and would otherwise be degraded w/out rev

Question 11

what is the greatest hurdle(at the molecular level) for HIV eradication?

Answer 11

integration into the genome; there is a large pool of latent virus just sitting in cells which there isnt a good drug target for

Question 12

role of Nef gene in HIV

Answer 12

down-regulates CD4, MHCI

induces FasL expression

Question 13

role of Vif gene in HIV

Answer 13

targets APOBEC3G which is then degraded; otherwise it would cause massive inactivating mutation in HIV genome

Question 14

role of Vpu gene in HIV

Answer 14

targets CD4 at the ER, preventing it from being expressed

Question 15

role of Vpr gene in HIV

Answer 15

can keep cell in G2 phase which is ideal for RNA production

Question 16

hurdles to producing a Vaccine for HIV

Answer 16

variably glycosylated envelope

highly mutagenic virus

integrates genome; latency

neutralizing epitopes only transiently expressed

Question 17

most common transmission of HIV in US

most common transmission of HIV ww

Answer 17

US - MSM

WW - heterosexual transmission

Question 18

fluids that transmit HIV

Answer 18

blood
breast milk
semen
vaginal/rectal fluids/secretions

Question 19

what would cause a false negative for HIV serologic testing

Answer 19

“window period”

time between infection and antibody/antigen production

Question 20

about how much time does it take for p24 antigen and HIV antibodies to appear after infection

Answer 20

p24 ~15 days (2 weeks)

antibodies ~25 days (3 weeks)

Question 21

when is pro-viral DNA tested for by PCR?

Answer 21

diagnosis of infants < 18 months of age

Question 22

symptoms of acute HIV infection

Answer 22

fever, lymphadenopathy, pharyngitis, rash, myalgia/arthralgia

**CD4 drops/viral load spikes @ start of HIV infection

Question 23

normal CD4 cnt

Answer 23

800-1050 cells/mm3

can range from 500-1400 in uninfected individuals

Question 24

HIV OI
pneumocystitis(PCP)

CD4 indication?
prophylaxis and when it should be given(primary/secondary)

Answer 24

CD4<200

give TMP-SMX as primary/secondary prophylaxis

Question 25

HIV OI toxoplasmosis CD4 indication? prophylaxis and when it should be given(primary/secondary)

Answer 25

CD4<100 and toxo IgG+ | give primary/secondary prophylaxis of TMP-SMX

Question 26

HIV OI cryptococcus CD4 indication? prophylaxis and when it should be given(primary/secondary)

Answer 26

CD4<100 | give only secondary prophylaxis of fluconazole

Question 27

HIV OI m. avium complex(MAC) CD4 indication? prophylaxis and when it should be given(primary/secondary)

Answer 27

CD4<50 | give only primary prophylaxis of azithromycin

Question 28

HIV OI CMV CD4 indication? prophylaxis and when it should be given(primary/secondary)

Answer 28

CD4<50 | give only secondary prophylaxis of valganciclovir

Question 29

OIs for HIV most comon at CD4 200-500

Answer 29

TB Oro-pharyngeal candidiasis VZV(shingles) kaposi's sarcoma(HHV-8)

Question 30

maraviroc(MVC) mechanism

Answer 30

binds CCR5 coreceptor; blocks HIV from entering cell wont work on mixed or CXCR4 virus profiles

Question 31

enfuvirtide(T-20) mechanism

Answer 31

prevents change in gp41 that allows fusion of HIV to cell membrane

Question 32

NRTIs

Answer 32

``` zidovudine stavudine didanosine tenofovir abacavir lamivudine emtricitabine ``` zestdla

Question 33

NRTI toxicity

Answer 33

mitochondrial toxicity causing neuropathy, myopathy, LAcidosis, hepatic steatosis, pancreatitis, lipoatrophy

Question 34

NRTI mechanism

Answer 34

stop chain elongation of RT

Question 35

NNRTI mechanism

Answer 35

binds at non-catalytic site on RT; inhibits functionality

Question 36

NNRTIs

Answer 36

nevirapine efavirenz etravirine rilpivirine

Question 37

resistance problems for NNRTIs

Answer 37

single mutations can cause cross-class resistance

Question 38

NNRTI toxicities

Answer 38

rash; can progress to stevens-johnson liver transaminase elevations/hepatitis

Question 39

efavirenze toxicity

Answer 39

CNS effects(hallucinations, insomnia) on top of class-common rash/liver enzyme elevation

Question 40

t1/2 of NNRTIs

Answer 40

VERY LONG; need to keep other meds going if stopping treatment to not cause resistance from NNRTI monotherapy due to long t1/2

Question 41

integrase inhibitors

Answer 41

raltegravir elvitegravir doultegravir ralph is an elite dueler

Question 42

ritonavir mechanism; indications

Answer 42

protease inhibitor cyp450 34a inhibitor; combined with other drugs to "boost" them

Question 43

are NNRTI's effective against HIV-2

Answer 43

NO, NO THEY ARENT

Question 44

protease inhibitor class toxicities

Answer 44

metabolic dysregulation - hyperlipidemia - increased potentiation of glucose intolerance GI upset - nausea, diarrhea Fat redistribution - buffalo hump - central/visceral adiposity

Question 45

ART treatment in naive patient should be composed of which drug classes?

Answer 45

2 NRTIs +.... - 1 NNRTI or - 1 PI(w/ritonavir boost) - 1 II

Question 46

what is the goal for the viral load after 1-4 months of therapy

Answer 46

see a log decrease in initial viral load