HIV Flashcards
Describe the structure of HIV.
2 copies of RNA w/ reverse transcriptase capsid protein p24 matrix protein p17 lipid membrane w/ gp41 transmembrane glycoprotein, used for fusion and entry gp120 docking glycoprotein
What are the 3 structural genes that code for HIV?
env: gp120 and gp41
gag: p24 capsid protein
pol: reverse transcriptase and aspartate protease and integrase
What does gp120 on HIV bind?
CCR5 on macrophages and dendritic cells early on in the infection
then CXCR4 on T cells later in the infection
How can you be immune to HIV?
homozygous for CCR5 mutation
hetero: slower progression
What are the tests used for the diagnosis of HIV?
ELISA: highly sensitive
WEstern Blot Assay: highly specific
Viral load tests–early on in course when ab aren’t made and for neonates that may screen as falsely pos. b/c of mom’s ab crossing the placenta
What does it take to make a diagnosis of AIDS?
- CD4
Describe the time course of HIV.
First month: asymptomatic
2-3 months: flu-like illness
3–? months: latent, feel fine, CD4 gradually drops
Final crisis when CD4 is low enough for opportunistic infections to take over
**this is interrupted by HIV therapy
What are the some opportunistic infections seen when CD4
candida thrush (scrapable)
EBV oral hairy leukoplakia (non-scrapable) lateral.
Bartonella-Bacillary angiomatosis
HHV8-Kaposi’s Sarcoma
Cryptosporidium–chronic watery diarrhea, acid fast oocysts in stool
HPV-anal or cervical cancer
What are some opportunistic infections seen in HIV patients w/ CD4
Toxoplasmosis-brain abscesses. multiple ring-enhancing lesions on MRI
AIDS dementia
JC-Progressive multifocal leukoencephalopathy-demyelination on MRI
PCP–ground glass on CXR from interstitial infiltrates
What are some opportunistic infections when CD4
Aspergillus: hemoptysis, cavitation on imaging
Cryptococcus-meningitis (India ink stain see capsules)
Candida esophagitis
CMV retinitis or esophagitis. Cotton wool spots, owl eye.
EBV-B cell lymphoma or CNS lymphoma w/ ring enhancing lesion
Histoplasma-oval yeast cells w/ macrophages
MAC/MAI–fever, night sweats, weight loss
Where is histoplasma endemic?
bird and bat dropping
Ohio and Mississippi River Valleys
When you see AIDs patient w/ pulmonary symptoms—what do you think?
PCP
TB
MAC/MAI
When you see an AIDS patient w/ meningitis, what do you think?
cryptococcus meningitis
When you see an AIDS patient w/ a ring-enhancing lesion what do you think?
Toxoplasmosis
primary lymphoma of CNS
What is the prophylaxis for CD4
What is involved in HAART?
3 drugs: 2NRTIs, 1 other drug
What is the MOA of protease inhibitors?
inhibit protease that cleaves mRNA products into functional parts
**all end in NAVIR
Ex: ritonavir
What are the main side effects of protease inhibitors?
GI complications
hyperlipidemia
inhibits CytP450
lipodystrophy
What are some special extra side effects of ritonavir?
pancreatitis
What are some special extra side effects of atazanavir?
increased bilirubin–jaundice
Which HIV drugs can cause nephrolithiasis (kidney stones)?
indinavir, atazanavir
What is the MOA of the NRTIs? What is a special thing that most of them require?
competitive inhibitors of reverse transcriptase
most of them require thymidine kinase phosphorylation for activation–they are nucleoside analogs
Exception: nucleotide analog is tenofovir
What is an important drug used for pregnant women and neonates who are HIV+ but not on HAART?
zidovudine
What are the NRTIs?
tenofovir zidovudine zalcitabine abacavir SLED stavudine lamivudine emtricitabine didanosine **some vudines
Which HIV drug causes bone marrow suppression…could see anemia (megaloblastic) or other things…
zidovudine
Which drugs cause pancreatitis and peripheral neuropathy?
ritonavir-pancreatitis pancreatitis and peripheral neuropathy- didanosine zalcitabine stavudine
Which drugs cause hepatic steatosis?
didanosine
stavudine
Which HIV drug causes a life-threatening hypersensitivity reaction?
abacavir
What is the MOA of NNRTIs?
noncompetitive inhibition of reverse transcriptase
don’t require phosphorylation by thymidine kinase for activation
What are the NNRTIs?
Delavirdine Etravirin Rilpivirine Nevirapine Efavirenz
Which HIV drug causes vivid dreams/worsens depression and can screen + for cannabinoids?
efavirenz
Which of the NNRTIs are teratogenic?
efavirenz
delavirdine
What are the integrase inhibitors?
raltegravir
What are the inhibitors of surface proteins of HIV?
gp120—inhibits CCR5 receptor, maraviroc (only if pt has ONLY CCR5 HIV)
gp41-inhibits viral entry–Enfuvirtide
What are the SE of raltegravir?
Nausea
rash
myopathy