Antivirals/HIV

Question 1

What is the definition of virustatic and what implications does this have for antiviral treatment? 


Answer 1

a) Drugs available block specific viral proteins that are involved in synthesis of viral components within the host cell.
b) Con: because it requires the virus to be replicating, a virustatic drug cannot target latent infections.

Question 2

What are the steps required for viral replication? 


Answer 2

a) Attachment and penetration of the virus to the host cell
b) Uncoating of the viral genome within the host cell
c) Synthesis of viral components within the host cell
d) Assembly of viral particles
e) Release of the virus to spread and invade other cells

Question 3

Influenza A: DOC and Goal of therapy

Answer 3

Zanamivir, Oseltamivir, Amantadine, Rimantadine
i) Goal of therapy: control symptoms, decrease productivity loss, prevent further complications, prevent infection spread within 48 hrs


Question 4

Influenza B: DOC and Goal of therapy

Answer 4

Zanamivir, Oseltamivir
i) Goal of therapy: control symptoms, decrease productivity loss, prevent further complications, prevent infection spread within 48 hrs


Question 5

Hepatitis B: DOC and Goal of therapy

Answer 5

1st line = Tenofivir, Entecavir, 2nd line = Interferon
i) Goal of therapy: Viral SUPPRESSION, NOT Curable, but achieve “functional cure”= UNDETECTABLE HBV DNA with seroconversion from HBsAG to the anti-HBs.

Question 6

Hepatitis C: DOC and Goal of therapy

Answer 6

Sofosbuvir/velpatasvir/voxilaprevir, Glecacprevir/pibrentasvir

i) Goal of therapy: CURE= sustained virologic response (SVR) defined as undetectable viral load at 12 weeks post-treatment
(1) GENOTYPE DRIVEN!! We mostly see Genotype 1

Question 7

HSV: DOC and Goal of therapy

Answer 7

Acyclovir, Valacyclovir, Famciclovir, Penciclovir, Docosanol
i) Goal of therapy: no cure currently available. Treatment can shorten duration and severity of flares. Prophylaxis decreases recurrence: immunocompromised or frequent recurrence.

Question 8

VZV: DOC and Goal of therapy

Answer 8

Acyclovir, Valacyclovir, Famciclovir
i) Goal of therapy: no cure currently available. Treatment can shorten duration and severity of flares. Prophylaxis decreases recurrence: immunocompromised or frequent recurrence.

Question 9

CMV: DOC and Goal of therapy

Answer 9

Ganciclovir, Valganciclovir, Foscarent, Cidofovir

i) Goal of treatment: Treatment can shorten duration and severity of illness???

Question 10

What is the purpose of ribavirin use in hepatitis C treatment, what should be monitored and how is it dosed?

Answer 10

a) Purpose: Treatment of HCV í inhibits viral replication contributing to synergistic effects
b) Lab monitoring: CBC every 2 weeks, and decrease dose if hemoglobin <10g/dL
c) Dosed: based on weight
i) <75kg = 600mg AM and 400mg PM
ii) >/= 75kg = 600mg BID
iii) Take with food

Question 11

What populations are at highest risk for CMV infections?

Answer 11

Immunosuppressed: HIV (less now with better drugs); at risk when CD4 <50 cells/mm3; organ transplant; end-organ disease 


Question 12

Which medication is Pregnancy Category X? 


Answer 12

a) Ribavirin - HCV treatment
i) Confirm 2 forms of birth control and negative pregnancy test up to 6 months post therapy
ii) TERATOGENIC

Question 13

What are the possible routes of transmission of the HIV virus?

Answer 13

a. Certain body fluids - blood, semen, pre-seminal fluid, rectal fluids, vaginal fluids, and breast milk
b. Contact with a mucous membrane or damaged tissue or be directly injected into the bloodstream
c. In US, HIV mainly spread by sex w/o condom and sharing needles

Question 14

What testing should be done prior to HIV drug treatment?

Answer 14

a. CD4 cell count: assess severity of immunosuppression and risk of opportunistic infections
b. HCV viral load: indicator of how quickly CD4 will decrease without ART
c. Resistance testing: present in 6-16% of patients
d. HBV/HCV serologies: chose regimen with HBV activity and avoid HCV DDIs
e. HLA-B*5701: If abacavir considered, due to risk of severe allergic reaction
f. Other tests: chem7, LFTs, CBC w/diff, fasting glucose N

Question 15

What is the goal of therapy for the treatment of HIV infection?

Answer 15

a. ART = antiretroviral treatment
b. Goal: reduce HIV-associated morbidity and prolong duration and quality of survival
i. Restore and preserve immunologic function
ii. Suppress HIV viral load
iii. Prevent HIV transmission

Question 16

Why is ritonavir included in many protease inhibitor-based HIV therapy regimens?

Answer 16

a. Considered an ART pharmacoenhancer
b. Most potent CYP inhibitor, decreasing metabolism of other PIs
c. Low doses to increase serum concentration = “ritonavir boosting”
d. Increase dosing interval
e. Increase barrier to resistance
f. Antiviral activity as protease inhibitor
g. GI intolerance, paresthesias, hyperlipidemia, asthenia, taste perversion, hyperglycemia, fat maldistribution

Question 17

What are the preferred regimens for the treatment of HIV?

Answer 17

a. Generally consists of 2 NRTIs PLUS one from the following classes: INSTI, NNRTI, or a PI with a pharmacoenhancer
i. Doletegravir/abacavir/lamivudine - ONLY for patients who are HLA-B*5701-negative
ii. Dolutegravir plus tenofovir/emtricitabine
iii. Elvitegravir/cobicistat/tenofovir/emtricitabine
iv. Raltegravir plus tenofovir/emtricitabine

Question 18

What is the preferred regimen for needle-stick prophylaxis (HIV)?

Answer 18

a. Emtricitabine (FTC) plus TDF (these 2 agents may be dispensed as Truvada, a fixed-dose combination tablet) plus raltegravir (RAL)
b. 28 days if HIV positive or unkown, if later determined HIV negative, can stop before 28 days

Question 19

What is PrEP? Which drugs are used?

Answer 19

a. Prevent HIV infection in people who don’t have HIV but are at high risk, lowering risk of getting HIV from sex by more than 90% and from injection drug use by more than 70%
b. Drugs used: tenofovir disoproxil/emtricitabine (Truvada) ONCE DAILY

Question 20

What is the preferred HIV regimen in pregnancy? What HIV drugs are known to be teratogenic?

Answer 20

2 NRTIs
i. Emtricitabine/tenofovir disoproxil fumarate OR abacavir/lamivudine OR lamivudine/zidovudine

1 ARV

• PIs
  1. Atazanavir + ritonavir
  2. Darunavir + ritonavir
• OR
  1. NNRTI
  2. Efavirenz (if initiated after the first 8 weeks of pregnancy)
• OR
  1. Integrase inhibitor reltagravir

Teratogenic: Efavirenz (aka Sustiva)