HIV

Question 1

What are the antiviral therapies used to treat HIV?

Answer 1

1) reverse transcriptase inhibitors:
- nucleoside RTI: zidovudine(AZT) and Lamivudine
-non-nucleoside RTI:
Efravirenz

2) protease inhibitors: lopinavir and ritonavir
3) other mechanisms: Raltegravir and Enfuvirtide

Question 2

What is zidovudine (Azidothymodine) AZT?

Answer 2

Protype-Nucleoside (thymidine analog) prodrug

Question 3

Drug used to treat HIV and hepatitis B virus ?

Answer 3

Lamivudine

Question 4

Drug used to prevent the transmission of HIV from infected mom to her baby (50%)?

Answer 4

Lamivudine

Question 5

What we should do to make the treatment of HIV more effective?

Answer 5

Use a combination of NRTIs with protease inhibitors to achieve highly active anti-retroviral therapy (HAART)
Initiate treatment consist of three drugs; 2 RTI & PI

Question 6

Indications of zidovudine or azidothymodine (AZT):

Answer 6

• in combination with other antivirals for HIV infection.
• used as mono therapy to prevent transmission of HIV from infected mom to her baby by >20%
• used to prevent post-exposure prophylaxis in healthcare workers.

Question 7

M.O.A of zidovudine:

Answer 7

• It’s phosphorylated to the active triphosphate by host cell kinase:
  1) insertion of activated ZTP into viral DNA by RT causes chain termination.
  2) It also inhibits RT activity by competing with endogenous nucleoside.

Question 8

AEs of zidovudine:

Answer 8

Myelosuppression (severe and dose-limiting)

Peripheral neuropathy

Question 9

When resistance to zidovudine occur?

Answer 9

When it’s used as sole agent, resistance results from multiple mutations in the gene that codes for RT.

Question 10

Indications for Efavirenz -N-NRTIs:

Answer 10

Used in combination with other antivirals to treat HIV-1 not HIV-2

Question 11

M.O.A of Efavirenz NNRTIs?

Answer 11

• Efavirenz does not require phospharization.
• is not incorporated into DNA strand.
• It act allosterically and inhibits HIV-1 RT

Question 12

AEs of Efavirenz?

Answer 12

• vivid dreams

- myelosuppression (less common compared to zidovudine)

Question 13

Indications of Lopinavir (protease inhibitor):

Answer 13

Used in combination with other antivirals to treat HIV-1 infection.

Question 14

M.OA of Lopinavir (protease inhibitor):

Answer 14

Competitive inhibitor of virus-soecific protease (aspartame protease) that cleave precursor polyproteins into vinous structural and functional proteins.

Inhibition of this enzyme will prevent the HIV maturation and remains non-infective.

Question 15

AEs of Lopinavir (important)

Answer 15

• Anemia.
• Hyperglycemia
• Lipodystrophy خلل في توزيع الدهون syndrome that associated with increased risk of MI.

Question 16

Indications of Ritonavir (protease inhibitor):

Answer 16

Used as booster of other protease inhibitors (lopinazvir) and not for its antiviral action,

Question 17

M.O.A of ritonavir (protease inhibitor):

Answer 17

Inhibit host enzyme that metabolizes other PIs leading to:

• increased plasma concert. Of these latter inhibitors.
• Reduce dose.
• Decrease AEs

Question 18

AEs of Ritonavir:

Answer 18

Same as lopinavir:
o Anemia and hyperglycemia
o Lipodystrophy syndrome that associated with increased risk of MI

Question 19

Clinical indications of Raltegravir (integrate inhibitor):

Answer 19

• used orallin combination with other antiviral agents for the treatment of HIV-1 infection.
• It’s generally reversal for antiretroviral drug resistance.

Question 20

It’s reversal for antiretroviral drug resistance:

Answer 20

Raltegravir (integrate inhibitor)

Question 21

M.O.A of Raltegravir ?

Answer 21

-inhibit HIV integrate > prevent insertion of viral DNA into human chromosome.

Question 22

AEs of Raltegravir:

Answer 22

Dizziness

Alteration in mood

Question 23

Clinical indications of ENfuvirtide:

Answer 23

• SC in combination with other antiviral agents for the treatment of HIV-1 infection.

Question 24

M.O.A of Enfuvirtide:

Answer 24

Bind to HIV gp41 protein and inhibit the fusion of HIV with the host cell membrane.

Question 25

AEs of Enfuvirtide:

Answer 25

Flu-like symptoms