Anti-Retrovirals

Question 1

Treatment Goals HIV

Answer 1

1) Limit Viral Load
2) Restore/Preserve Immune function(CD4+ cells)
3) Limit adverse effects
4) Reduce HIV morbidity and mortality

Question 2

How early should you begin treating an HIV patient?

Answer 2

IMMEDIATELY. if have serious infection, treat infection then begin HAART

Question 3

What is the minimum of care for an HIV patient

Answer 3

HAART
3 drug regiment (2Nucleoside inhibitors and 1 NonNucleoside inhibitor)
Protease inhibitors (1or2 with 2 Nucleoside RT inhibitors)
Integrase Inhibitors (Raltegravir and Tenofovir/emtricitabine)

Question 4

Treatment Failure

Answer 4

Must begin with completely new regiment.

Addition of only 1 new drug to old regiment=monotherapy

Question 5

Mutation Rate

Answer 5

Rapid because RT is VERY error prone

-Probability of resistance is proportional to viral load

Question 6

Therapy Consequences

Answer 6

• Therapy is lifelong–> non-adherence leads to resistance
• HIV lipodystrophy=longterm metabolic effect from combo meds
• Half lives of all other drugs are effected by the HIV regiment–>affects CYP3A
• Immune Reconstitution Syndrome=reversal of immunodeficiency in pts with low CD4–> accelerated inflammatory response to opportunistic infection

Question 7

Zidovudine

Answer 7

prototype nucleoside(thymidine) analog(competitive)
Similar to acyclovir
-mildly toxic
-oral dose

Resistance-prolonged monotherapy promotes cross resistance to other NRTIs
-usually given with Lamivudine

Uses: used as monotherapy to prevent mother-child transfer
-HIV infection with lamuvidine

Adverse:Severe anemia, Lactic acidosis and hepatic steatosis

Question 8

Lamivudine

Answer 8

Used in combo therapy with Zidovudine
-->maintains low viral load so resistance doesnt form to zidovudine
HIV infection with zidovudine
-->MUCH LESS TOXIC THAN zidovudine
-->TREATS Hep B infection

Question 9

Emtricitabine

Answer 9

like zidovudine

Only take once per day

Question 10

Tenofovir

Answer 10

ONLY NUCLEOTIDE

Treats HIV and HBV

Question 11

Efavirenz

Answer 11

Non-Nucleoside Reverse Transcriptase inhibitor
Allosteric inhibition of HIV RT
-Does not effect host DNA poly
RESISTANCE: HIV2=resistant, highly susceptible to single nuc changes is allosteric binding pocket
-orally effective

Use:HIV1 infection, pts who failed therapy that lacked NNRTI

Adverse:Teratogen, Dizziness insomnia and drowsiness seen in 50% of users

Question 12

Nevirapine

Answer 12

Similar to Efavirenz

Adverse: LIVER TOXICITY

Question 13

Lopinavir

Answer 13

Protease Inhibitor
Competitive inhibitor of HIV protease
Prevents cleavage of gag-pol precursor proteins and virus fails to mature

Oral dose
THE ACTIVE ANTIRETROVIRAL piece

Question 14

Ritonavir

Answer 14

Oral dose
BOOSTS ACTIVITY of LOPINAVIR BY INHIBITING CYP3A4
–>any other CYP inhibiting drugs would increase efficacy of Lopinavir

Question 15

Atazanavir

Answer 15

Protease inhibitor
less likely to cause lipodystrophy
-dont give with Proton pump inhibitors, decrease efficacy

Question 16

Enfuvirtide

Answer 16

Fusion inhibitor
binds to HIV and prevents envelope from fusing with CD4 cell
GIVEN IV, 2x day
ONLY HIV DRUG GIVEN IV
Use:addition to existing when evidence of resistance

Adverse-erythema at infusion sites
-risk of pneumonia

Question 17

Maraviroc

Answer 17

Fusion Inhibitor
Blocks CCR5 and prevents binding of viral protein

TARGETS HOST PROTEIN TO BLOCK VIRUS

Question 18

Raltegravir

Answer 18

Integrase Inhibitor
prevents insertion into host genome
Used in therapy with HAART
generally well tolerated