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antithymocyte globulin

answer

1. developed in horses, administered to selectively inactivate/destroy T cells when they are causing acute rejection of a transplanted organ despite other immunosuppressive therapy

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hyperacute

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5. organ rejection that occurs within minutes due to preformed antibodies

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muromonab CD3

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9. approved for use only when there is a glucocorticoid-resistant flare-up in the acute rejection of a transplanted organ

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ritonavir

answer

17. weaker HIV protease inhibitor discovered to be a potent inhibitor of CYP3A4, reason it is now routinely used to "boost" other protease inhibitors

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protease

answer

18. HIV enzyme that cleaves at the N- terminal side of Pro residues in the long polypeptides (e.g., gag, pol) packaged into newly budded virions to release the enzymes and cell components required for their metamorphosis into a mature virus capable of causing infection

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preferred NRTI backbone

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19. the combination of tenofovir disoproxil fumarate and emtricitabine is this for treatment-naïve HIV patients due to its safety and efficacy, and also due to the convenience of a once/day co-formulation +/- efavirenz

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lamivudine

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21. earlier cytidine-like NRTI, interesting in that HIV can develop resistance to it relatively quickly but doing so increases reverse transcriptase fidelity, slows replication, and thereby helps to increase the long- term effectiveness of zidovudine

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nnrti

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24. class of drugs that selectively inhibits only HIV-1 reverse transcriptase; binds to a distant hydrophobic pocket in a manner that causes a conformational change and noncompetitively inhibits enzymatic activity

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renal insufficiency

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26. reason to avoid some antiretroviral drugs such as indinavir and decrease the dosages of others

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indinavir

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27. early protease inhibitor requiring 3X/day dosing, now perhaps more noteworthy for its ability to cause crystaluria

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etravirine

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29. NNRTI approved for use in treatment-experienced people infected with HIV since it still works after HIV mutations that cause resistance to some other NNRTI

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CD 8

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30. T cell population that surveys cell protein synthesis by examining fragments of those proteins inserted into the MHC class 1 proteins on their cell surface, and destroys those cells that are recognized as synthesizing foreign proteins

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enfuvirtide

answer

33. a 36 aa peptide that inhibits formation of a 6-helix bundle critical for HIV fusion with the host cell membrane, drug is a last resort since expensive and must be administered subQ 2X/day

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P glycoprotein

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34. aka MDR1, a transporter that interacts with many drugs and site at which competition can influence the drug toxicities

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navir

answer

37. ending of generic drug name that identifies the drug as an HIV protease inhibitor

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maraviroc

answer

39. will block HIV entry if an expensive test with a long turnaround time shows that the virion requires the CCR5 co- receptor

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HIV DNA

answer

43. cells infected with HIV typically only have one copy of this, unlike the virion which characteristically possess two copies of its precursor

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hypercholesterolemia

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46. side effect of therapy with cyclosporine and sirolimus but not tacrolimus

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pregnant woman

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49. should be given anti-retroviral therapy as soon as possible, irrespective of viral load or CD4 count, but efavirenz should not be used during the first trimester

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mitochondria

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51. blockade of DNA polymerase here is thought to be responsible for some of the adverse effects associated with some NRTI

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everolimus

answer

52. a sirolimus-like drug but with a shorter half-life (~30 hrs vs 62 hrs), means steady-state levels can be achieved faster and also that drug will disappear faster if discontinued due to adverse effects

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bone marrow suppression

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54. major adverse effect of most anti- proliferative drugs, increases susceptibility of transplant recipient to infection and bleeding

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guanine

answer

55. its de novo synthesis is blocked by mycophenolate

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B cells

answer

56. proliferate and differentiate into antibody-producing plasma cells when fragments of a molecule that was captured by the surface expression of their unique antibody and then inserted into MHC class II antigens on their surface is recognized as foreign by a helper T cell

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glucocorticoids

answer

58. pharmacological doses blunt acute organ rejection by suppressing NFkappaB driven gene expression in cells triggered by the recognition of a foreign antigen

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sirolimus

answer

61. binds to FKB12, but inhibits protein kinase mTOR, which in lymphocytes is an important downstream signaling component of IL-2 receptor-stimulated proliferation and differentiation

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reflex tachycardia

answer

63. does not occur when nifedipine or hydralazine are administered to a heart transplant recipient

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tegravir

answer

64. portion of generic drug name indicating that the drug is an HIV integrase inhibitor

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tacrolimus

answer

65. aka FK-506, binds to the immunophilin FKB12 to inhibit calcineurin phosphatase activity; exerts beneficial effects in organ transplantation similar to those caused by cyclosporine

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prophylaxis

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66. reason, for example, for administering basiliximab immediately before kidney transplantation and for a few days after, during what is referred to as (not in notes) "transplant induction therapy"

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IL-2

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68. molecule released by activated T cells that binds to receptors on their surface to promote the characteristic T cell response (= growth, proliferation and differentiation of effector T cells)

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disoproxyl

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69. prodrug formulation of tenofovir, a phosphorylated adenosine analog, to overcome its otherwise poor bioavailability

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hirsutism

answer

71. potential cosmetic challenge with cyclosporine that is not a problem with tacrolimus

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env

answer

72. HIV gene that encodes for gp120 and gp41

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allograft rejection

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74. blocking this is a reason to take drugs such as prednisone, cyclosporine and mycophenolate

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CXCR4

answer

76. emergence of this tropism in HIV renders it resistant to maraviroc

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lymphocytes

answer

79. cell population unable to use guanine salvage pathways, therefore must synthesize new guanine during proliferation (= reason for cell-selectivity of mycophenolate)

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tenofovir

answer

83. adenosine analog that is the only NRTI nucleotide (i.e., has a phosphate already attached, so only needs 2 more to be active), an NRTI of choice due to its relative safety, long half-life and co-formulation in once/day pills

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blood transfussion

answer

84. carries by far the greatest risk of transmitting HIV, but now a negligible cause for HIV transmission in the US (risk ~ 1:1.4 million)

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CYP3A4

answer

86. cytochrome P450 isozyme that is inhibited, induced, etc., by a wide range of drugs including several antiretroviral drugs, which leads to potentially troublesome drug interactions

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hypertension

answer

87. consequence of the renal afferent arteriolar constriction caused by cyclosporine and tacrolimus in solid organ transplant recipients

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OKT3

answer

88. widely known name for muromonab- CD3 ("nab" rather than "mab" is correct spelling), the original and still- used mouse monoclonal antibody against human CD3 (= T cell receptor) that causes its rapid internalization and thereby prevents T cell activation

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AIDS

answer

89. symptoms of this appear when HIV RNA copy numbers are high in plasma and CD4+ lymphocyte numbers are low

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saquinavir

answer

90. first HIV protease inhibitor, its short half-life caused a troublesome pill burden and it is among the agents well-known for promoting irreversible lipodystrophy with long-term use

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adenosine

answer

1. can cause a prolonged and potentially life-threatening asystole in a transplanted (=denervated) heart

question

IL-1

answer

2. proinflammatory signaling molecule released by antigen-presenting cells that facilitates activation of lymphocytes

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treatment failure

answer

3. reason for a thorough evaluation of patient history and contemplation of new strategy rather than adding a single new drug to an HIV treatment regimen or stopping treatment altogether

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lymphocele

answer

4. accumulation of lymph in unusual space (e.g., retroperitoneal cavity after renal transplant), risk is increased by sirolimus

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atazanavir

answer

6. when boosted, a first-choice protease inhibitor for treatment- naïve HIV patients due to its long half-life and reduced side effects, but can cause unconjugated hyperbilirubinemia not associated with hepatitis

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efavirenz

answer

7. the current NNRTI of choice for treatment-naïve HIV patients, in part because it is co-formulated with tenofovir and emtricitabine for convenient once/day dosing

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nrti

answer

8. a two-drug combination from this antiretroviral drug therapy class with zidovudine as its prototype provides the backbone for current HIV treatment strategies

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CD-4

answer

10. T cell population that surveys MHC class II molecules for unrecognized peptide fragments derived from phagocytosis, and, upon recognizing a foreign molecule, activates macrophages, stimulates production of antibodies, etc.

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kidney

answer

11. the first and still by far most transplanted organ

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phosphorylation

answer

12. required of NRTI for them to be active

question

nevirapine

answer

13. an NNRTI, early studies with it demonstrated the importance of combination therapy in treating HIV after the virus in ~1/3 of patients developed resistance to it after a single monotherapy exposure

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mutations

answer

14. typically 4-5 are required for HIV to develop resistance to protease inhibitors, reason resistance is slow to develop and seldom a cause for treatment failure

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zidovudine

answer

15. thymidine analog and the first anti-retroviral drug discovered, this NRTI is still in widespread use in resource-poor settings due to its well-known tolerability, toxicity and efficacy profiles

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prednisone

answer

16. example of a drug that causes sequestration of circulating lymphocytes and also decreases their number via apoptosis

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pregnancy

answer

18. wise to take extra measures to prevent this if taking anti- proliferative agents

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calcinurin inhibitors

answer

20. most effective immunosuppressive drugs in routine use

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tolerizing

answer

22. effect observed with sirolimus, means that foreign antigens present during its use are not rejected immediately when/if sirolimus is discontinued

question

darunavir

answer

23. when boosted, a first-choice protease inhibitor for treatment- naïve HIV patients due to its long half-life and reduced side effects, but can cause sulfa drug hypersensitivity reactions

question

renal damage

answer

25. attempts to minimize this are the reason that sirolimus is added to lowered doses of cyclosporine or tacrolimus

question

acute

answer

28. refers to organ rejection that develops over days to weeks in association with primary activation of T cells in response to antigens expressed on the surface of allograft cells and/or on antigen presenting cells that have phagocytosed allograft cell proteins

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pol

answer

31. HIV gene that contains reverse transcriptase, protease, integrase, etc.

question

mycophenolate

answer

32. non-competitive reversible inhibitor of inosine monophosphate dehydrogenase

question

emtricitabine

answer

35. cytidine analog, one of the least toxic anti-retroviral drugs and an NRTI of first choice for HIV treatment-naïve patients due to its long half-life and co- formulation with tenofovir +/- efavirenz

question

cytokine release syndrome

answer

36. refers to the unpleasant consequences (e.g., fever, chills, dyspnea, nausea, possibility of anaphylactoid shock) associated with the administration of an antibody generated in a different species; can be especially bad during initial administration but then decreases over time, in part because of concurrent administration of glucocorticoids

question

basiliximab

answer

38. mouse monoclonal antibody against human IL-2 receptor used to inhibit T cell activation/proliferation, tolerability was improved by creating a chimera in which the antibody contains a human constant region

question

accelerated

answer

40. organ rejection that happens within days due to reactivation of sensitized T cells

question

raltegravir

answer

41. first generation integrase inhibitor, seems likely to be displaced from preferred therapy list by new drugs elvitegravir and dolutegravir since their longer half-lives permit once daily dosing

question

Cushing syndrome

answer

42. pharmacological dosages of exogenous glucocorticoids can also cause this (no 's in answer)

question

azathioprine

answer

44. anti-proliferative agent that helped make allogeneic transplantation possible, it is somehow more effective at blocking de novo purine synthesis and DNA replication than direct administration of its active metabolite, 6-mercaptopurine

question

nephrotoxicity

answer

45. dose-limiting for both cyclosporine and tacrolimus, especially cyclosporine

question

terminate elongation

answer

47. NRTIs do this during reverse transcriptase mediated synthesis of proviral DNA

question

lopinavir

answer

48. HIV protease inhibitor only available as a boosted combination, inhibits both HIV-1 and HIV-2, and often works after failure of another PI-containing regimen

question

CNS toxicity

answer

50. common side effect of efavirenz, but typically subsides and rarely leads to discontinuation of the drug

question

xenotransplantation

answer

53. encompasses the dream of transplanting pig organs into humans

question

lung

answer

57. organ in addition to liver for which sirolimus is contraindicated as anti-rejection therapy after transplantation

question

gag

answer

58. HIV gene that contains the nucleocapsid core and matrix proteins

question

cyclosporine

answer

59. first drug discovered that caused immunosuppression without bone marrow suppression, its binding to cyclophilin blocks calcineurin- mediated dephosphorylation of NFAT

question

stavudine

answer

60. among early thymidine NRTI, notable for causing many of the toxicities associated with the drug class including CNS toxicity, fat wasting, and the ability to cause lactic acidosis and hepatic steatosis

question

myopathy

answer

62. among the toxicities associated with some NRTI that is thought to be due to inhibition of DNA polymerase gamma

question

lipodystrophy

answer

67. ~irreversible disfiguring re- distribution of body fat associated with HIV and its treatment

question

integrase

answer

68. enzyme responsible for insertion of retroviral DNA into the human genome, and an excellent drug target since mammalian genomes lack enzymes with this capability

question

intercourse

answer

70. risk of acquiring HIV infection during this is fortunately much lower than during childbirth or blood transfusion

question

NK cells

answer

73. among the cells that contributes to acute allograft rejection, for example, via antibody-dependent cell-mediated cytotoxicity

question

allopurinol

answer

75. xanthine oxidase inhibitor used to prevent gouty arthritis and uric acid nephropathy in patients predisposed to hyperuricemia or having it due to excess cell turnover from cancer +/- chemotherapy; its use mandates a reduction in azathioprine dosage

question

chronic

answer

76. refers to organ rejection occurring over months to years for which there is ~no effective therapy, characterized by interstitial fibrosis, thickened vascular walls, etc.

question

aids info

answer

77. government run website that provides latest consensus guidelines for treatment of HIV in the US

question

CD-4 count

answer

78. having this fall to <350 cells/mm3 currently has an AI level of support for initiation of antiretroviral therapy

question

HBV

answer

80. also sensitive to some HIV drugs such as tenofovir disoproxil fumarate and emtricitabine; discontinuation of these drugs can cause a disease flare-up

question

diabetes

answer

81. risk of developing this is significant following renal transplantation, especially when immunosuppressive drugs are added to glucocorticoids

question

abacavir

answer

82. the only NRTI that is a guanosine analog, relatively safe in most but can cause a unique and potentially fatal hypersensitivity syndrome in those with the HLA- B*5701 locus

question

NFAT

answer

85. its migration into the lymphocyte nucleus after its dephosphorylation by calcineurin is crucial for the generation of gene products such as IL-2 that are characteristic of T cell activation

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