Switching from PIs to NNRTIs has similar effect on TC/HDL ratio as use of lipid lowering drugs in the management of dyslipidaemia
6 December 2006. Related: Conference reports, Side effects, Lipodystrophy and metabolic complications, HIV 8th Glasgow 2006.
Simon Collins, HIV i-Base
Marc van der Valk presented an analysis comparing results from different approaches to the management of dyslipidaemia in an analysis from the D:A:D cohort. [1]
The study primarily looked at the different effect from using lipid lowering drugs (LLD) compared to switching from PI- to NNRTI-based regimens. This was informed by an earlier randomised study (Calza, AIDS 2005) that reported greater reductions in mean total cholesterol from baseline of -46% with pravastatin, and -38% with bezafibrate, compared to -27% and -10% after switching from a PI to either nevirapine or efavirenz respectively. [2] Concerns raised in the Calza study include seeing a greater than expected effect from use of lipid lowering agents, compared to results from clinical trials with these drugs
In the D:A:D study, patients were identified who were NNRTI-naive and who had confirmed total cholesterol >6 mmol/l on PI-based regimens for > 6 months. They compared results from 221 patients using LLD to 208 patients who switched their PI to an NNRTI, and to 1,463 control patients who made no intervention. Baseline values and results at 12 months are summarised in Table 1. The changes reported remained significant after adjustment for sex, age, HIV RNA and CD4, smoking, history of CVD, use of CVD drugs, diabetes, previous PI exposure and ethnicity. P values reported below refer to strategy arm compared to control.
Each strategy produced different effects on lipid parameters. Total cholesterol fell in all groups, but reductions were greater with LLD compared to switching. Both strategies were significantly better than the control arm (p<0.0001 and p=0.02, compared to control, respectively). Increases in HDL were only significant compared to control in the switch group (p=0.0001; compared to p=0.27 in LLD group). Both groups had a similar effect in reducing TC:HDL ratio (p=0.03, LLD; p=0.06 switch). Changes in LDL were greater in the LLD group (p=0.0004) compared to the switch group (p=0.06); while reductions in triglycerides were greatest in the switch group (p=0/0001) vs LLD (p=.0007).
Because of the significant differences in some baseline parameters, the researchers then analysed results stratified by baseline values. LLD resulted in most pronounced effect on total cholesterol and LDL, especially in those with highest baseline values, with minimal effect on HDL. Switching resulted in greater increases in HDL, irrespective of baseline values. And both strategies led to similar reductions in TC/HDL ratio.
The study noted that the changes observed in controls could suggesting some regression to the mean, or possible selection of those in whom intervention was withheld in view of declining lipid values, perhaps related to changes in diet and exercise (not recorded in the study). Limitations of the study also include problems of selection bias (with LLD drugs chosen for patients with greater dyslipidaemia) and no ability to look at role of individual LLDs.
Table 1: Baseline characteristics and results
| LLD | Switch | Control | p-value | |
|---|---|---|---|---|
| n | 221 | 228 | 1463 | |
| Baseline (median, mmol/L) | ||||
| Total cholesterol (TC) | 7.6 | 7.1 | 6.7 | 0.0001 |
| LDL | 5.4 | 5.1 | 4.9 | 0.0001 |
| TG | 3.6 | 2.6 | 2.6 | 0.0001 |
| HDL | 1.1 | 1.1 | 1.2 | 0.003 |
| TC:HDL | 6.6 | 6.1 | 5.8 | 0.001 |
| Results (mean changes at 12 months, mmol/L) | ||||
| Total cholesterol (TC) | -1.02 | -0.66 | -0.40 | |
| LDL | -0.92 | -0.71 | -0.45 | |
| TG | -0.82 | -1.10 | -0.18 | |
| HDL | +0.08 | +0.18 | +0.01 | |
| TC:HDL | -1.48 | -1.48 | -0.48 | |
References:
- Van Der Valk M, Friis-Moller N, Sabin C et al. Effect of interventions to improve dyslipidaemia. 8th International Congress on Drug Therapy in HIV Infection, 12-16 November 2006, Glasgow. Oral abstract PL12.2.
- Calza L Manfredi R Colangeli V et al. Substitution of nevirapine or efavirenz for protease inhibitor versus lipid-lowering therapy for the management of dyslipidaemia. AIDS 2005 July 1; 19 (10): 1051-1058.