HIV antiretroviral therapy

Question 1

During acute HIV – patient have _____ viral loads and is at_____ risk for transmitting virus during this time – this is a challenging situation as pts do not often know they are infected at this time and hiv ab test may often be neg – need to check viral load

Answer 1

high

Question 2

benefits of early therapy general points (4)

Answer 2

1. Reduced risk of HIV-associated morbidity and mortality
2. Restore immune function
3. Decrease inflammation and immune activation
4. Suppress HIV RNA/prevent transmission

Question 3

HIV enters host cells by a complex process that involves sequential attachment of the HIV viral protein _______ to the host CD4 receptor followed by binding of ______ to either the CCR5 or CXCR4 co-receptor. This tight binding allows tight membrane fusion and release of the HIV genome in the host cell. HIV genome is SSRNA – this is converted to DNA by reverse transcriptase.

Answer 3

HIV enters host cells by a complex process that involves sequential attachment of the HIV viral protein gP120 to the host CD4 receptor followed by binding of gP120 to either the CCR5 or CXCR4 co-receptor. This tight binding allows tight membrane fusion and release of the HIV genome in the host cell. HIV genome is SSRNA – this is converted to DNA by reverse transcriptase.

Question 4

Viral DNA is carried into the host cell nucleus and inserted into the host cell genome by viral enzyme ______. Transcription and Translation occur – viral proteins are formed and are packaged into viral particles by the__________. These viral particles are released from the host cell and can go on to infect other cells.

Answer 4

Viral DNA is carried into the host cell nucleus and inserted into the host cell genome by viral enzyme integrase. Transcription and Translation occur – viral proteins are formed and are packaged into viral particles by the protease enyzme. These viral particles are released from the host cell and can go on to infect other cells.

Question 5

Binds viral surface gp41 to prevent fusion of the viral and cellular membrane, and insertion of viral genome into cell.

Answer 5

enfuvirtide

Question 6

Prevents HIV entry into cell via binding to CCR5 cell surface protein. Requires viral “tropism” test to determine CCR5 receptor dependence

Answer 6

Maraviroc

Question 7

NRTI MOA

Answer 7

DNA chain terminators:

Converted to triphosphate form intracellularly
Lack 3 prime hydroxyl group
Stops DNA chain growth after incorpation by RT

Question 8

Older NRTIs inhibit ___________ and are more toxic than newer NRTIs

Answer 8

mitochondrial replication

Question 9

older NRTI mito-tox: (3)

Answer 9

1. lactic acidosis
2. peripheral neuropathy, hepatic steatosis, pancreatitis
3. subcutaneous fat loss

Question 10

Preferred NRTI; Included in first line regimens

Side Effects
Nephrotoxicity
Loss of bone mineral density

Answer 10

tenofovir

Question 11

Cytidine nucleoside reverse transcriptase inhibitors
Minimal toxicity
Similar drugs with similar atomic structure
Available as component of fixed dose combinations
Active against HBV

Answer 11

Lamviudine/ Emtricitabine

Question 12

Assoc with increased risk of MI in some cohort studies

Should not be started if HLA-B*5701 test result is positive
Hypersensitivity Reaction

Answer 12

Abacavir

Question 13

Bind and deform the active site of reverse transcriptase
Does not block chain elongation
Lower barrier to resistance
Not active against HIV-2

Answer 13

NNRTI such as efavirenz and rilpivirine

Question 14

NNRTI that has potential teratogenic SE and SE include impaired concentration, dizziness, trouble sleeping, vivid dream/nightmares and depression

Answer 14

efavirenz

Question 15

newer NNRT; recommended as part of initial HIV regimen if you can not use a protease inhibitor but not in HIV viral load >1000,000.

potential hepatoxicity

Answer 15

rilpivirine

Question 16

Block post translational maturation of viral proteins which is essential for production of mature, infectious viral particles
Often given with metabolic booster to increase drug levels

Answer 16

protease inhibitors

Question 17

protease inhibitors resistance is ______ to occur and requires multiple changes in viral _______ gene

Answer 17

protease inhibitors resistance is slow to occur and requires multiple changes in viral protease gene

Question 18

portease inhibitors associated with which type of tox.?

Answer 18

metabolic tox such as insulin resistance, hyperlipidemia, lipohypertrophy (acc. of fat)

Question 19

Atazanavir can lead to indirect bilirubinemia due to _______ inhibition

Answer 19

UGT1A1

**this enzyme is deficient in pt. with Gilbert

Question 20

Protease inhibitor used for its boosting effect by inhibiting cytochrome P450 3A4 enzyme and thus the protease inhibitor level is increased. thus be careful of drug interaction

Answer 20

ritonavir

Question 21

Pharmacokinetic Enhancer- Inhibits cytochrome p450 3A4 enzymes – drug interactions

Answer 21

cobicistat

Question 22

HIV integrase inhibitors blocks the integrase enzyme which is essential for the viral DNA copy

Answer 22

to integrate into the host cell DNA and initiate production of viral components

Question 23

HIV integrase inhibitors as a class:

Bictegravir
Dolutegravir
Elvitegravir-administered with cobicistat-assoc with drug interactions
Raltegravir

Answer 23

• potent inhibitors
• few side effects
• high barrier to resistance

Question 24

dolutegravir in pregnancy

Answer 24

Recent data indicates increased risk of neural tube defects in infants born to women receiving dolutegravir at time of conception

Question 25

integrase inhibitor that requires cobicistat as a pharmacokinetic enhancer

Answer 25

elvitegravir, thus not as used as often

Question 26

goal of ART

Answer 26

decrease viral load to level below detection (8-16 weeks) and to see an increase in CD4 count (about 1 year)

Question 27

Combination Antiretroviral Therapy is generally 2 NRTIs with a 3rd active drug (integrase inhibitor is preferred but in some cases protease inhibitor or NNRTI may be ok)

Answer 27

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Question 28

ART should be offered to everyone with HIV

Answer 28

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Question 29

PrEP what to use?

Answer 29

Tenofovir/emtricitabine