NRTIs

MOA

NNRTIs

Inhibits HIV reverse

transcriptase enzyme by
competing with adenosine,
guanosine, thymidine, and
cytosine to grow proviral DNA
chain.
-Lactic Acidosis and
hepatic steatosis
(abdominal distention, n/v/d,
low CO2, anion gap >16)
-Stavudine and Didanosine
have the greatest risk for ADR

Inhibits HIV-1 reverse

transcriptase by binding
adjacent to the active site,
inducing a conformational
change that inactivates the
enzyme
All can cause rashes and
hepatotoxicity

Indications

HIV-1 and HIV-2

Comments

ADR

DRUG:

PIs

Entry Inhibitor

Integrase Inhibitors

Inhibits the enzyme HIV

protease by binding to its
active site. Prevents the
cleavage of gag-pol
precursorincomplete &
non-infectious virions
-Significant GI effects
-Paresthesia
-Hyperglycemia &
insulin resistance
-Dyslipidemia
-Hepatotoxicity
-Lipohypertrophy

CCR5 receptor antagonist

prevents CCR5 tropic HIV
entry into cells

HIV integrase strand

transfer inhibitor

Maraviroc- Dizziness,
orthostatic hypotension,
hepatoxicity

N/D, h/a

HIV-1 only

HIV-1 and HIV-2

-NRTIs must undergo

phosphorylation to be active
vs. virus
-First class of ARV drug
approved.
-All are renally eliminated

-Parent molecule is active

(unlike NRTIs)
-2nd class of drug to be
approved

- CYP3A4 substrate

CCR5-trophic HIV-1, any pt

resistant to multiple AR
agents
-CI in CVD, Liver disease,
Infection
-CYP450 substrate
-Expensive ($900-$1000
per month)

Combination therapy in
pts resistant to other ARV
drugs
Raltegravir (Isentress)

Zidovudine (AZT)
Lamivudine (3TC)
Abacavir (ABC)
Emtricitabine (FTC)
Tenofovir (TDF)

Efavirenz (EFZ)

Maraviroc (Selzentry)
Enfuvirtide (Fezeon)

Raltegravir

-Ritonavir is most potent

inhibitor (Boosted
therapy--used in combo
with other PIs to increase
their levels)
Ritonavir (RTV)
Nelfinavir (NFV)
Lopinavir-Ritonavir
Atazanavir (ATV)

ANTIRETROVIRAL DRUGS FOR HIV AND AIDS

Enfuvirtide- Inj site Rxn.

Expensive ($1000 per

month)

Nucleoside/Nucleotide Analogue Reverse Transriptase Inhibitors (NRTIs)

MOA: Inhibits HIV reverse transcriptase enzyme by competing with adenosine, guanosine, thymidine, and cytosine to grow proviral DNA chain.

ZIDOVUDINE(Retrovir)

LAMIVUDINE(Epivir)

ABACAVIR(Ziagen)

-Adults & Children

-Post-exposure prophylaxis
-Prenatal/perinatal
transmission to baby by HIV
infected mother, NOT as
monotherapy for mother

-HIV 1, 2 pts
-Hep B

-HIV 1, 2

ADR

-h/z, n/v/d, anorexia, fatigue

-Bone marrow suppression
-Nail discoloration
-Lipoatrophy

GI effects-(biggest
complaint)

Comment
s

-First ARV for HIV

-Post exposure prophylaxis
(basic) in combo with
Lamivudine

-Cytosine analogue
-Best tolerated of all
NRTIs

Indication
s

EMTRICITABINE(Emtriv
a)
-Dual NRTI drug
-Preferred initial
HAART regimen
QD dosing
-Hep B

TENOFOVIR DF (Viread)

-Fatal hypersensitivity
rxn (3-5% of pts)fever,
rash, GI, cough
-Black box warning

-Similar to other NRTIs

-Caution with h/a and
unique
hyperpigmentation of
the palms

-Renal insufficiency RARE

-Osteoporosis

-Guanosine Analogue

-Cytosine analogue
-Long half-life- Can take
w/o regards to meals

-Adv: Already has one phosphate

group so it only requires
diphosphorylation to be activated
-Adenosine analogue

-Dual NRTI
-Preferred intial HAART
regimen
-Hep B

Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTIs)

MOA: Inhibits HIV-1 reverse transcriptase by binding adjacent to the active site, inducing a conformational change that inactivates the enzyme

EFAVIRENZ (Sustiva) EFZ

Indications

-NNRTI portion of initial preferred HAART regiment

-HIV-1 ONLY

ADR

-Rash (MC)
-CNS effects: dizziness, h/a, insomnia, AMS, vivid dreams, nightmares, hallucinations

Comments

Adm: MUST be taken on an empty stomach

CI in 1st trimester of preg
Use with caution in pts with unstable psychiatric dz.

Protease Inhibitors (PIs)

MOA: Inhibits the enzyme HIV protease by binding to its active site. Prevents the cleavage of gag-pol precursorincomplete & non-infectious virions

RITONAVIR (RTV)

NELFINAVIR(NFV)

LOPINAVIR-RITONAVIR

ATAZANAVIR (ATV)

Indications

HIV 1,2

HIV 1,2

HIV 1,2
-Can be used as PI portion for
initial preferred HAART
regimen

HIV 1,2

ADRs

-GI effects
-Altered taste sensation
-Paresthesias
-Hypertriglyceridemia
-Pancreatitis

-Diarrhea
-Flatulence

-Hyperlipidemia
-Diarrhea

-Similar to other PI except less

dyslipidemia
-Hyperbilirubinemia (d/c if total BIR >5x
ULN or Jaudice)

Comments

-Not well tolerated in high doses

Boosted therapyused, in low
dose, in combo with other PIs to
increase their levels
-Potent CYP3A4 inhibitor, also
CYP2D6

**Does not have to be boosted

with RitonavirCan boost with
food**
-No cross resistance to other PIs

-Ritonavir inhibits the rapid

inactivation of Lopinavir by CYP3A4

-Greater specificity for HIV protease than

other available PIs

-Do not use once-daily in preg

-Metabolized/Inhibitor of CYP3A4
-Requires an acidic medium
-CI with PPI
-Separate dosing required w/ H2
blockers & antacids

Entry/Fusion Inhibitors
MOA: CCR5 receptor antagonistprevents CCR5 tropic HIV entry into cells

ENFUVIRITIDE (T-20)

MARAVIROC (MVC)

Indications

CCR5-trophic HIV-1, any pt resistant to multiple AR agents

Pts resistant to multiple ARV agents

Preg Cat (B)

ADRs

-Injection site RXN

-Dizziness, orthostatic hypoTN, hepatotoxicity

Comments

Inj Adm:
-Supplied as Dry powder for reconstitution
-Stored as room temp prior to reconstitution
-Syringe, diluents, alcohol supplied with product

-Caution in CVD, Liver Dz, Infxn

-CYP450 substrate

Integrase Inhibitors
MOA: HIV integrase strand transfer inhibitor- Prevents HIV from getting into host DNA

RALTEGRAVIR (ISENTRESS)
Indications

Combination therapy in pts resistant to other ARV drugs

ADRs

N/V, Headache

Comments

-Less DDIs
-$1,000 per month

ARV TX FAILURE:
VIROLOGIC FAILURE (MC!)
o
HIV RNA is still in the blood 1 year after initiation of treatment
OR if it is detected again after ARVs had previously lowered it
to undetectable.
IMMUNOLOGIC FAILURE
o
CD4 increase of <25-50 cells/uL in the first year of therapy, or
a decline in CD4 count to below the baseline.
CLINICAL PROGRESSION

The occurrence of HIV-related events or a decline in physical

health after >3 months of therapy

CAUSES OF TX FAILURE
Patient factors
o
CD4, Viral load, co -morbidities)
Suboptimal adherence
ARV toxicity and intolerance
Pharmacokinetic problems
Suboptimal drug potency
Viral resistance

Antiretroviral Combination Regimen consists of

either:

1-NNRTI + 2-NRTI OR
1-PI(w/ boost of ritonavir) + 2-NRTI

NNRTI:
Efavirenz
PI:
Atazanavir + Ritonavir (CI in PPIs)
Darunavir + Ritonavir
Fosamprenavir + Ritonavir
Lopinavir/Ritonavir
2-NRTI: