Tuberculosis and HIV

Question 1

HIV life cycle

Answer 1

gp 120 and gp 41 attach to CD4 T cells –> CXCR 4 or CCR 5 –> into cell –> viral RNA to DNA by reverse transcriptase –> integrase puts DNA into cell host DNA –> transcription and translation –> protease puts viral replicated into cell wall and spreads

Question 2

Maraviroc

Answer 2

binds to CXCR 4 and CCR 5 so HIV cannot bind and enter cell –> need genetic testing of HIV virus to make sure which receptor it uses

Question 3

Enfuvirtide

Answer 3

binds to gp41 on HIV virus, not allowing gp41 the facilitation of viral entry

Question 4

Abacavir
Zidovudine
Lamivudine
Emtricitabine

Answer 4

NRTI (nucleoside)
completely inhibits reverse transcriptase, inserts into viral DNA and causes termination
Requires phosphorylation by cellular enzymes to be active
S.E.: general hepatic toxicity
- Z ->granulocytopenia
- L/E -> best tolerated

Question 5

Tenofovir

Answer 5

NRTI (nucleotide)
completely inhibits reverse transcriptase, inserts into viral DNA and causes termination
Requires phosphorylation by cellular enzymes to be active
S.E.= N/V, diarrhea, renal failure

Question 6

Efavirenz

Etravirine

Answer 6

NNRTI
Inhibits reverse transcriptase at separate site from NRTI, doesn’t require phosphorylation
S.E. = rashes and hepatic cy-P450

Question 7

Atazanavir
Ritonavir
Darunavir

Answer 7

Protease Inhibitors
inhibit protease activity that is required for full maturation of virus –> don’t become infectious
S.E. = GI, hepatotoxicity, hyperglycemia, insulin resistance
lots of cyp-450 interactions

Question 8

Raltegovir

Answer 8

Integrase Inhibitor

binds integrase –> prevents strand transfer (the final step in provirus integration)

Question 9

Rifampin

Answer 9

inhibits DNA-dependent RNA polymerase
Ramps up CYP-450 (be careful with HIV patients and meds)
Red/orange body fluids
Hepatotoxicity

Question 10

Isoniazid

Answer 10

decreases synthesis of mycolic acids (needs bacterial catalse-peroxidase to convert to active metabolite)
only drug used prophylaxis for TB
Some people are rapid acetylators (slow acetylators –> liver damage) –> monitor liver function
S.E. = neurotoxicity, hepatotoxicity, B6 deficiency (use pyridoxine)

Question 11

Pyridoxine

Answer 11

used for Isoniazid toxicity (PLP transamination)

Question 12

Aminoglycosides

Answer 12

Streptomycin
inhibits formation of initiation complex by irreversibly binding 30S subunit –> causes misreading of mRNA
nephrotoxic, neurotoxic, ototoxic, teratogen
Can be inactivated by acetylation or phosphorylation
Does not enter cell –> used for extracellular treatment of TB

Question 13

Pyrazinamide

Answer 13

unknown mechanism –> maybe intracellular acidity?

hyperuricemia, hepatotoxic

Question 14

Ethambutol

Answer 14

decreases carbohydrate polymerization of mycobacterium cell wall
optic neuropathy –> color blindness (dose related)
don’t use in kids!

Question 15

Sensitivity

Answer 15

TP/ TP+FN

Question 16

Specificity

Answer 16

TN/TN+FP

Question 17

PPV

Answer 17

TP/TP+FP

Question 18

NPV

Answer 18

TN/TN+FN

Question 19

HIV confirmation

Answer 19

Negative ELISA is good enough for any population

Positive ELISA –> 5% chance that it was false positive –> perform Western blot (99%)

Question 20

Lung nodule’s

Answer 20

Neoplasm
Granuloma
Abscess, pneumonia, pulmonary infarct
Likelihood of malignancy is proportional to nodule size, pts age, history of smoking

Question 21

Significance of calcification of lung nodule

Answer 21

calcification –> generally not malignant cancer

- could be granuloma, abscess, hamartoma, etc

Question 22

Significance of cavitation of lung nodule

Answer 22

a lucency within a zone of pulmonary consolidation, a mass, or a nodule; hence, a lucent area within the lung that may or may not contain a fluid level and that is surrounded by a wall
- most likely indicates necrosis

Question 23

Mycobacterium tuberculosis

Answer 23

Rod-shaped, spore forming, obligate aerobe, acid-fast bacilli
High content of mycolic acids
VF : Lipoarabinomannan -> pathogen-host interactions, facilitates survival in macrophages
CatG -> protects against oxidative stress (also required for isoniazid to work)
Cord Factor -> inhibits macrophage maturation and induces TNF-alpha
SLOW GROWER

Question 24

Active TB Clinical Picture

Answer 24

SYMPTOMATIC –> CONTAGIOUS
can be either primary or secondary
Sx = cough, dyspnea, hemoptysis, weight loss, fever, chills

Question 25

Latent TB Clinical Picture

Answer 25

ASYMPTOMATIC –> NOT CONTAGIOUS
can see findings of (+) mantoux or CXR
Mycobacterium are sitting in the granuloma

Question 26

PPD (TB skin test)

Answer 26

subdermal injection
Th1 cells recruit macrophages --> induration and redness (test is for induration, not redness!)
Immunocompromised >5 mm (+)
High Risk >10 mm (+)
Normal Healthy >15 mm (+)

Question 27

Reason for combo therapy for TB?

Answer 27

Using the combo therapy of 4 drugs GREATLY reduces the chance for drug resistance

Question 28

Why add a low dose of Ritonovir to AIDS regimen?

Answer 28

Used at low doses, it increases the serum concentrations of the other protease inhibitors (Ritonovir inhibits cyp3A4 which metabolizes the other PIs)