Maraviroc

CCR5 antagonist HIV CCR5

receptor CD4+ cell

HIV 1,2,3 USFDA 2007

maraviroc
4
1). maraviroc1,2,3

Bioavalibility 23%-33% Cmax

33%-60% AUC 33%-50%

plasma protein 76% 14-18

CYP3A inactive metabolites3
CYP2D9 , CYP2D6 ,CYP2D19
2 20%
(8% ) 76%
(25% )
2).
300 mg 2

CYP3A inhibitors inducers1,2,3
2.1 CYP3A inhibitors
protease inhibitors ( tipranavir/ritonavir),
delavirdine, ketoconazole, itraconazole, clarithromycin, nefazodone,
and telithromycin maraviroc

maraviroc 150 mg 2
2.2 CYP3A inducers efavirenz, rifampin, carbamazepine, phenobarbital, and
phenytoin maraviroc

maraviroc 600 mg 2
2.3

3).maraviroc

Gulick 5 double-blind, placebo-controlled, phase 3

studies(MOTIVATE 1 MOTIVATE 2 )

( optimized background therapy : OBT)

3 1. OBT + maraviroc 300 mg 2. OBT + maraviroc 300
mg 2 3.
OBT 48 virologic
immunologic response
maraviroc

HIV-1 RNA (P<0.001) CD4+

T-cells

HIV-1 RNA(log10 copies/mm3) Increases CD4+ T-cells (cells/mm3)

OBT+ maraviroc OD OBT+ maraviroc BID OBT OBT+ maraviroc OD OBT+ maraviroc BID OBT
MOTIVATE 1 -1.66 -1.82 -0.80 113 112 54
MOTIVATE 2 -1.72 -1.87 -0.76 122 128 69

: P<0.001 maraviroc maraviroc

maraviroc

HIV-1 RNA CD4+ T-cells

OBT (P<0.001)
2

?
viral load CD4 count
viral load
3- 4
CD 4 count 3 6

(Antiretroviral therapy in HIV infected pregnant women)

..

1.

CD4 < 350 cells/mm3

1.1.

Highly Active Antiretroviral Therapy (HAART)

 efavirenz
zidovudine
nevirapine CD4+ count > 250 cells/mm3 ( nevirapine

CD4 < 250 cells/mm3)

= zidovudine (300) + lamivudine (150) 1 12
lopinavir/ritonavir (200/50) 2 12

1.2.

zidovudine 300 mg 1 3 600 mg

1.3.

()

1.4.

()

GA > 35 : zidovudine syrup 4 mg/kg/dose 12 4

GA 30 35 : zidovudine syrup 2 mg/kg/dose 12 2
zidovudine
syrup 2 mg/kg/dose 8 2

GA < 30 : zidovudine syrup 2 mg/kg/dose 12 4

2.

CD4 > 350 cells/mm3

2.1.

HAART 14
zidovudine
nevirapine CD4+ count > 250 cells/mm3 ( nevirapine

CD4 < 250 cells/mm3)

zidovudine monotherapy ( HIV RNA levels < 1000
copies/mL)

= zidovudine (300) + lamivudine (150) 1 12

lopinavir/ritonavir (200/50) 2 12

2.2.

zidovudine 300 mg 1 3 600 mg
nevirapine 200 mg zidovudine monotherapy

2.3.

()

nevirapine zidovudine (300) + lamivudine (150) 1 12 7

2.4.

()

GA > 35 : zidovudine syrup 4 mg/kg/dose 12 4

GA 30 35 : zidovudine syrup 2 mg/kg/dose 12 2
zidovudine
syrup 2 mg/kg/dose 8 2
GA < 30 : zidovudine syrup 2 mg/kg/dose 12 4

3.

3.1.

HIV antiretroviral drug-resistance testing

(detectable viral load viral load >

1000 copies/mL 6 )

zidovudine zidovudine

 efavirenz ( efavirenz zidovudine (300) +

lamivudine (150) 1 12 lopinavir/ritonavir (200/50) 2 12

3.2.

zidovudine 300 mg 1 3 600 mg

3.3.

()

3.4.

()

GA > 35 : zidovudine syrup 4 mg/kg/dose 12 4

GA 30 35 : zidovudine syrup 2 mg/kg/dose 12 2
zidovudine
syrup 2 mg/kg/dose 8 2
GA < 30 : zidovudine syrup 2 mg/kg/dose 12 4

4.

4.1.

zidovudine 300 mg 1 3 600 mg nevirapine 200 mg

2 nevirapine
( zidovudine 600 mg )

4.2.

()

zidovudine (300) + lamivudine (150) 1 12 lopinavir/ritonavir (200/50) 2

12 CD4
CD4 > 350 cells/mm3 : zidovudine (300) + lamivudine (150) 1 12
lopinavir/ritonavir (200/50) 2 12 4

CD4 < 350 cells/mm3 :

nevirapine ( zidovudine) zidovudine CD4

< 350 cells/mm3

4.3.

()

zidovudine syrup 4 mg/kg/dose 12 lamivudine syrup 2 mg/kg/dose 12 4

6 nevirapine syrup 4 mg/kg/dose 24 2 4

ziduvudine + lamivudine NVP 2

1. (virological failure)

viral load 400 copies/mL 6

viral load 50 copies/mL 12
viral load 50 copies/mL viral load 50 copies/mL

2.
(immunological failure)

CD4 50 cells/mm3 12
CD4 30%
%CD4 3
CD4

1. CD4

2. Viral load

36
virus

viral load 1000 copies/mL

8 12

3. CBC

4 8 (zidovudine)

4. AST/ALT

4 8 (nevirapine)

5. GCT

(lopinavir/ritonavir)
24 28 4

1. Zidovudine (AZT 200 mg/tab)

: , bone marrow suppression (anemia, neutropenia)

2 3
Hb < 8 g/dL Hct < 24% AZT
ferrous folic acid supplementation
AZT d4T

2. Lamivudine (3TC 150 mg/tab)

3. Stavudine (d4T 30 mg/tab)

: peripheral neuropathy, lactic acidosis

Peripheral neuropathy 50

d4T ddI

Lactic acidosis

lactate

 5 mmol/L arterial pH

d4T ddI

supportive treatment
d4T ddI

4. Nevirapine (NVP 200 mg/tab)

: skin rash, hepatotoxicity

Skin rash 2 3 diffuse maculopapular rash

mucous membrane involvement

antihistamine NVP
Hepatotoxicity 1 2 serum transaminase
elevation clinical hepatitis CD4 250 cells/mm3,

AST ALT , HBV HCV NVP 200 mg 24

2 , NVP CD4 > 250 cells/mm3
AST/ALT > 2.5 upper limit NVP NVP
EFV LPV/r

5. Tenofovir (TDF)

: nephrotoxicity, bone mineral density

Nephrotoxicity serum
creatinine , proteinuria, glycosuria, hypokalemia

serum creatinine

 TDF osteomalacia
TDF (fetal
growth retardation)

6. Efavirenz (EFV, stocrin 600 mg/tab)

: hepatotoxicity, teratogenicity
Hepatotoxicity NPV
Teratogenicity anencephaly, anophthalmia, microphthalmia cleft palate

EFV myelomeningocele anophthalmia EFV

EFV

7. PIs LPV/r

: insulin resistance, hyperlipidemia,

Insulin resistance
PIs
GCT / OGTT

GDM GCT

/ OGTT 24 28
Hyperlipidemia
PIs LDL, total
cholesterol, triglyceride ATV/r PIs

fasting lipid profile 3 6

hyperlipidemia

 PIs

ergot alkaloids methergine

severe vasoconstriction methergine oxytocin

1 ,

(Classes of antiretroviral drugs, Food and Drug Administration pregnancy (FDA) pregnancy category
classification and common side effects)

Drug class

FDA category

Nucleoside and nucleoside analog reverse transcriptase inhibitors (NRTIs)

Zidovudine (AZT)

Stavudine (D4T)

Lamivudine (3TC)

Abacavir (ABC)

Zalcitabine (ddC)

Tenofovir (TDF)

Emtricitabine (FTC)

Didanosine (ddI)

Non-nucleoside reverse transcriptase inhibitors (NNRTIs)

Nevirapine (NVP)

Efavirenz (EFV)

Delavirdine (DVL)

Protease inhibitors

Lopinavir / ritonavir (LPV/r, Kaletra)

Indinavir (IDV)

Amprenavir (APV)

Fosamprenavir (FPV)

Ritonavir (RTV)

Nelfinavir (NFV)

Atazanavir (ATV)

Saquinavir (SQV)

Darunavir (DRV)

Entry inhibitors

Enfuvirtide (ENF)

Maraviroc

Integrase inhibitors

Raltegravir (RAL)

 (fixed-dose combination)
1.GPO-vir Z

= AZT (250) + 3TC (150) + NVP (200)

2.GPO-vir S30

= d4T (30) + 3TC (150) + NVP (200)

3.Zilavir

= AZT (300) + 3TC (150)

4.Lastavir

= d4T (30) + 3TC (150)

5.Kaletra

= LPV (200) + RTV (50)

6.Truvada

= TDF (300) + FTC (200)

1.

1. Atazanavir (Reyataz) 2. Tenofovir (TDF) 3. Efavirenz GPO 4. Efavirenz (Stocrin)

5. Zidovudine (Antivir) 6. Lastavir 7. Lamivudine (Lamivir) 8. Lopinavir / ritonavir GPO

9. Stavudine (Stavir) 10. Nevirapine (Neravir) 11. GPO-vir S30 12. GPO-vir Z

2. Zidovudine (AZT)

3. Stavudine (D4T)

4. Lamivudine (3TC)

5. Nevirapine (NVP)

6. Lastavir

7. GPO-vir Z

8. GPO-vir S30

9. Efavirenz (EFV)

10. Efavirenz (EFV)

11. Lopinavir / ritonavir

12. Atazanavir (ATV)

13. Tenofovir (TDF)