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Switching from PI to Trizivir or Nevirapine Due to Lipid Abnormalities
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Reported by Jules Levin
Spanish researchers presented at the 9th EACS (Oct 2003) conference week 36 results from the study of patients with abnormal lipids who switched from their first PI regimen to either Trizivir or nevirapine based regimens. The SIMPLIFICATION HAART Study examines the changes in lipids for patients with suppressed viral load on their first PI regimen who simplified the regimen to 3 NRTIs (Trizivir) or 2 NRTIs (Combivir) plud nevirapine. The study evaluates virologic, immunologic, and metabolic outcomes, as well as adherence and patient satisfaction. (Bonioch and colleagues, Lluita contra la SIDA” Found HUGTi Pujol, Barcelona).
Summary. The mean values for lipid profiles improved in this study after patients switched to NVP or Trizivir. As you can see from the detailed results below after switching from a PI regimen to Trizivir or nevirapine based regimens the mean LDL-cholesterol (bad cholesterol) and triglycerides decreased. The mean percent of patients with mild, moderate, and severe elevations in total cholesterol decreased. For patients switching to Trizivir, HDL (good cholesterol) decreased from 44 to 37 mg/dL. For patients switching to NVP, HDL cholesterol was 45 at baseline and 47 mg/dl after 36 weeks. CD4 counts were maintained and there was 1 reported viral failure (on Trizivir) 36 weeks after switching.
Patients received Trizivir (Group 1), 1 pill twice daily or Nevirapine plus Combivir (AZT/3TC), 2 pills twice daily. This is a multi center, prospective, open-label randomized study for 124 patients.
The study authors presented references for past published articles on the metabolic profiles for NVP and ABC.
NVP & Metabolic Profile
Negredo AIDS 2002
Ruiz JAIDS 2001
Van der Valk AIDS 2001
Carr AIDS 2001
Martinez AIDS 1999
Abacavir & Metabolic Profile
Lafeuilade HIV Clinical Trials2003
Maggiolo Clin Inf Dis 2003
Carr JAMA 2002
Walli Eur J Med Red 2001
Carr AIDS 2001
Patients were on their first HAART regimen (PI or EFV plus nukes). Viral load was suppressed for at least 6 months prior to study. There was no viral load rebound after undetectability, CD4s were >100. Patients were evaluated at baseline and every 3 months for lipids, viral failure, adherence, CD4 response. Viral load rebound from undetectability was confirmed in two consecutive determinations.
Dislipidemia Criteria from European Athreosclerosis Society
Total Cholesterol
>5.2 mmol/l
>200 mg/dL
LDL Cholesterol (bad cholesterol)
>3.4 mmol/L
>130 mg/dL
HDL Cholesterol (good cholesterol)
<0.9 mmol/L
<35 mg/dL
Triglycerides
>2 mmol/L
>200 mg/dL
RESULTS
After 36 weeks followup. Most patients had been on a PI regimen. There were 68 patients in Group 1 and 66 in Group 2. 89% in group 1 were on PI regimen and 94% from Group 2 were on PI regimen.
CD4 Response
At baseline, mean CD4 counts were 635 and 614 in groups 1 and 2; after week 36 Cd4 count was 712 in Group 1 (TZV) and 632 in Group 2. Authors reported there were no differences between the two arms.
Viral Failure
The authors reported there were no failures in Group 2 (NVP) and 1 patient at week 24 in the TZV arm (1.5%).
TOTAL CHOLESTEROL
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| TZV |
Mild |
Moderate or severe |
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>5.2 mmol/L |
>6.62 mmol/L |
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>200 mg/dL |
>255 mg/dL |
| Baseline |
49% |
18% |
| W12 |
23% |
2%* |
| W24 |
24% |
3.7%* |
| W36 |
19% |
4%* |
| NVP |
| Baseline |
62% |
18% |
| W12 |
46% |
4%* |
| W24 |
38% |
3.7%* |
| W36 |
19% |
4.8%* |
| *p<0.05 |
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Mean total cholesterol (mmol/L) was 5.62 for NVP at baseline and 5.02 at week 36; for TZV, mean total cholesterol was 5.38 at baseline and 4.82 at week 36.
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| TZV |
Mean Total Chol (P=BL vs W12, W24, & W36) |
| BL |
5.38 mmol/L (207 mg/dL) |
| W12 |
4.57 (p=0.001) (176 mg/dL) |
| W24 |
4.46 (p=0.0003) (172 mg/dL) |
| W36 |
5.02 (p=ns) (193 g/dL) |
| NVP |
Mean Total Chol |
| BL |
5.62 mmol/L (216 mg/dL) |
| W12 |
5.13 (p=0.01) (198 mg/dL) |
| W24 |
5.18 (p=ns) (199 mg/dL) |
| W36 |
4.82 (p=0.03) (186 mg/dL) |
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LDL-CHOLESTEROL
Mean LDL-cholesterol was 3.54 mmol/L at baseline for NVP group and 2.9 at week 36. For TZV group it was 3.6 mmol/L at baseline and 2.89 at week 36. Bad cholesterol (LDL) was reduced from >130, which is cutoff for the criteria listed above for the European Athreosclerosis Society, to below 130.
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| TZV |
Mean LDL-Chol |
| BL |
3.6 mmol/L (138 mg/dL) |
| W12 |
2.87 (p=0.003) (110 mg/dL) |
| W24 |
2.71 (p=0.0009) (104 mg/dL) |
| W36 |
2.9 (p=0.02) (111 mg/dL) |
| NVP |
Mean LDL-Chol |
| BL |
3.54 mmol/L (136 mg/dL) |
| W12 |
3.12 (p=0.05) (120 mg/dL) |
| W24 |
3.32 (P missing) (128 mg/dL) |
| W36 |
2.89 (p=0.01) (111 mg/dL) |
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HDL-CHOLESTEROL
Mean HDL-Cholesterol was 1.18 mmol/L at baseline for NVP group and 1.23 at week 36. For TZV group, HDL-Cholesterol was 1.15 at baseline and 0.97 at week 36.
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| TZV |
Mean HDL-Chol |
| BL |
1.157 mmol/L (44 mg/dL) |
| W12 |
1.11 (42 mg/dL) |
| W24 |
1.06 (40 mg/dL) |
| W36 |
0.97 (37 mg/dL) |
| NVP |
Mean HDL-Chol |
| BL |
1.183 mmol/L (45 mg/dL) |
| W12 |
1.32 (50 mg/dL) |
| W24 |
1.259 (48 mg/dL) |
| W36 |
1.23 (47 mg/dL) |
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TRIGLYCERIDES
TG decreased a mean of 0.41 mmol/L (36 mg/dL) in TZV group (from 2.19 to 1.78 mmol/l or from 194 mg/dl 158 mg/dl,) and 0.56 mmol/L (49 mg/dl) in NVP group (from 2.4 to 1.85 mmol/l, from 213 to 164 mg/dl) (p=ns).
The authors concluded that both simplified regimens maintained immunologic improvement and viral suppression. And Both simplified therapies showed an early improvement in lipid abnormalities, particularly in Total Cholesterol and LDL-Cholesterol in patients switching from their first HAART PI regimen.
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