HIV Flashcards
gp41, HIV
transmembrane protein(hookshot) associates with gp120 on envelope surface
p17, HIV
matrix proteins
p24, HIV
capsid proteins
p7, HIV
nucleocapsid proteins
transmission of HIV
mucosal: sex or mother»child @birth
parenteral: direct injection
how does HIV invade the body when it goes the mucosal route?
- DCs trap HIV and pass to/infect CD4+ Tcells
- Breach in endothelium
- Transcytosis
describe HIV cell surface interactions when infecting a cell
gp120 binds CD4
gp120 transforms and binds CCR5 or CXCR4
gp41 is exposed and extends to target cell, initiating fusion
tRNA lysine role in HIV infection
primer for RT
structural genes for HIV
gag, pol, env
gag and pol code polyproteins that are cleaved into respective structural proteins after translation
trans-activator genes?
what do they do?
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
what is the greatest hurdle(at the molecular level) for HIV eradication?
integration into the genome; there is a large pool of latent virus just sitting in cells which there isnt a good drug target for
role of Nef gene in HIV
down-regulates CD4, MHCI
induces FasL expression
role of Vif gene in HIV
targets APOBEC3G which is then degraded; otherwise it would cause massive inactivating mutation in HIV genome
role of Vpu gene in HIV
targets CD4 at the ER, preventing it from being expressed
role of Vpr gene in HIV
can keep cell in G2 phase which is ideal for RNA production
hurdles to producing a Vaccine for HIV
variably glycosylated envelope
highly mutagenic virus
integrates genome; latency
neutralizing epitopes only transiently expressed
most common transmission of HIV in US
most common transmission of HIV ww
US - MSM
WW - heterosexual transmission
fluids that transmit HIV
blood
breast milk
semen
vaginal/rectal fluids/secretions
what would cause a false negative for HIV serologic testing
“window period”
time between infection and antibody/antigen production
about how much time does it take for p24 antigen and HIV antibodies to appear after infection
p24 ~15 days (2 weeks)
antibodies ~25 days (3 weeks)
when is pro-viral DNA tested for by PCR?
diagnosis of infants < 18 months of age
symptoms of acute HIV infection
fever, lymphadenopathy, pharyngitis, rash, myalgia/arthralgia
**CD4 drops/viral load spikes @ start of HIV infection
normal CD4 cnt
800-1050 cells/mm3
can range from 500-1400 in uninfected individuals
HIV OI
pneumocystitis(PCP)
CD4 indication?
prophylaxis and when it should be given(primary/secondary)
CD4<200
give TMP-SMX as primary/secondary prophylaxis
HIV OI
toxoplasmosis
CD4 indication?
prophylaxis and when it should be given(primary/secondary)
CD4<100 and toxo IgG+
give primary/secondary prophylaxis of TMP-SMX
HIV OI
cryptococcus
CD4 indication?
prophylaxis and when it should be given(primary/secondary)
CD4<100
give only secondary prophylaxis of fluconazole
HIV OI
m. avium complex(MAC)
CD4 indication?
prophylaxis and when it should be given(primary/secondary)
CD4<50
give only primary prophylaxis of azithromycin
HIV OI
CMV
CD4 indication?
prophylaxis and when it should be given(primary/secondary)
CD4<50
give only secondary prophylaxis of valganciclovir
OIs for HIV most comon at CD4 200-500
TB
Oro-pharyngeal candidiasis
VZV(shingles)
kaposi’s sarcoma(HHV-8)
maraviroc(MVC) mechanism
binds CCR5 coreceptor; blocks HIV from entering cell
wont work on mixed or CXCR4 virus profiles
enfuvirtide(T-20) mechanism
prevents change in gp41 that allows fusion of HIV to cell membrane
NRTIs
zidovudine stavudine didanosine tenofovir abacavir lamivudine emtricitabine
zestdla
NRTI toxicity
mitochondrial toxicity causing neuropathy, myopathy, LAcidosis, hepatic steatosis, pancreatitis, lipoatrophy
NRTI mechanism
stop chain elongation of RT
NNRTI mechanism
binds at non-catalytic site on RT; inhibits functionality
NNRTIs
nevirapine
efavirenz
etravirine
rilpivirine
resistance problems for NNRTIs
single mutations can cause cross-class resistance
NNRTI toxicities
rash; can progress to stevens-johnson
liver transaminase elevations/hepatitis
efavirenze toxicity
CNS effects(hallucinations, insomnia) on top of class-common rash/liver enzyme elevation
t1/2 of NNRTIs
VERY LONG; need to keep other meds going if stopping treatment to not cause resistance from NNRTI monotherapy due to long t1/2
integrase inhibitors
raltegravir
elvitegravir
doultegravir
ralph is an elite dueler
ritonavir mechanism; indications
protease inhibitor
cyp450 34a inhibitor; combined with other drugs to “boost” them
are NNRTI’s effective against HIV-2
NO, NO THEY ARENT
protease inhibitor class toxicities
metabolic dysregulation
- hyperlipidemia
- increased potentiation of glucose intolerance
GI upset - nausea, diarrhea
Fat redistribution
- buffalo hump
- central/visceral adiposity
ART treatment in naive patient should be composed of which drug classes?
2 NRTIs +….
- 1 NNRTI or
- 1 PI(w/ritonavir boost)
- 1 II
what is the goal for the viral load after 1-4 months of therapy
see a log decrease in initial viral load
