HAART所致的血脂异常和胰岛素抵抗

ZDV/3T C + EFV (n = 254)
P Value
TC • mmol/L
24 0.62
36 0.94
.005
LDL cholesterol
10
• mmol/L
0.26
16 0.41
NS
HDL cholesterol
13
• mmol/L
0.34
12 0.31
NS
1. 2.
TArGribas J, et al. J •GamllamntoJl/EL, et al.
Eron JJ, et al. Lancet. 2006;368:476-482.
ARTEMIS: DRV/RTV 和 LPV/RTV对血脂的影响比较
ng/mL
TG
250
DRV/RTV + TDF/FTC
LPV/RTV + TDF/FTC
mM
2.9
5.0
TC:HDL Ratio
Mean TG Level ( ± SE) Mean TC:HDL Ratio (±
CASTLE: ATV/RTV vs LPV/RTV at Week 48
60
Median Change From BL (%)
50
40
30
*
20
10
0
Difference
TC
LDL
estimates (%) -9.5
-2.9
Molina JM, et al. CROI 2008. Abstract 37.
LDL
24 25 HDL
非核苷类药物对血脂的影响： EFV vs
NVP at Week 48
• 48周, 多中心, 开放, 随机 未治 疗 (N = 1216)
– NVP 400 mg QD (n = 220)
– NVP 200 mg BID (n = 387)
– EFV 600 mg QD (n = 400)
• EFV组血脂变化较大 (combination NVP + EFV arm excluded from lipid analysis)
van Leth F, et al. PLoS Med. 2004;1:e19.
10
0
-10 TC LDL *P < .05 vs NVP. †P < .001 vs NVP.
HDL
10 7 0 TC
1. Squires K, et al. J Acquir Immune Defic Syndr. 2004;36:1011-1019. 2. Malan DR, et al. J Acquir Immune Defic Syndr. 2008;47:161-167.
24 16
– NVP 400 mg + EFV 800 mg QD (n = 209)
– All plus d4T + 3TC
EFV + 3TC/d4T
50
40 40
35
31
30
27
Pooled NVP + 3TC/d4T 49†
43
34 *
20 20
Mean Change in Lipids From Baseline to Week 48 (%)
ATV + ZDV/3TC (n = 404)
50
EFV + ZDV/3TC (n = 401)
ATV + d4T + 3TC (n = 105)
50
ATV/RTV + d4T + 3TC (n = 95)
40
30
*
21
20
*
*
24
18 13
40
30
20
16
10 2
0 TC
*P < .0001
1 LDL
Acquir JAMA.
I2m0m004u.;4n02e942D:1e9fic1-S2y0n10d.3r..4621008;47:.7044-778.
HDL
†
5.9
-4.1 TG TC:HDL
GS 934 and GS 903: TDF与嘧 啶类似物对血脂的影响
▪ 前瞻性, 随机, 双盲研究
▪ TDF 对血脂水平影响较小
Mean Δ From BL to Week 144, mg/dL
GS 934[1]
TDF + FTC + EFV (n = 255)
100
FPV/RTV 700/100 mg BID +
ABC/3TC (n = 434)
80
60
LPV/RTV SGC 400/100 mg BID + ABC/3TC (n = 444)
66 60
39
40
33
20
39 41
29 23
0
TC
HDL
LDL
TG
▪ Lipid effects comparable between arms
3.0
24 8 1216 24 36
48
Time (Wks)
343
320
305
346
313
301
BMS-034 & BMS-089: 激动剂的阿扎那韦 和无激动剂的 ATV 在48周对血脂的影响
BMS-034[1]
BMS-089[2]
Median Change From BL (%) Median Change From BL (%)
ATV/RTV + TDF/FTC (n = 440) LPV/RTV + TDF/FTC (n = 443)
*
*P < .0001
*
HDL -3.8
Non-HDL -11.6
TG -25.2
Median Change From BL (%)
KLEAN: FPV/RTV vs LPV/RTV at Week 48对脂代谢的影响
1. Schambelan M et al. JAIDS 2002; 31(3):257-75. 2. 11th CROI, 2004, Abstract 739.
3. 11th CROI, 2004, Abstract 736. 4. 11th CROI, 2004, Abstract 737.
大型临床试验
SE)
4.5
200
2.3
4.0
NCEP cutoff

150
1.7
3.5
100
24 8 1216 24 36
Time (Wks)
DRV/RTV n = 343
320
LPV/RTV n = 346
313
1.1 48
306 301
De Jesus E, et al. ICAAC 2007. Abstract 718b.
HAART所致的血脂异常和 胰岛素抵抗
HIV/ART 毒性: 血脂异常
• 抗病毒治疗之前，HIV/AIDS人群HDL & LDL (especially HDL) 下降，而甘油三酯水 平升高。
• HAART后LDL和总胆固醇升高,甘油三酯 也升高。
• 大部分的蛋白酶抑制剂、核苷类药物、部 分非核苷类药物可引起脂代谢异常，但程 度不同。