Triglyceride levels returned to normal levels in one third of patients with elevated triglyceride levels within 12 weeks of switching from d4T to tenofovir, according to findings from the Recover study, a large Spanish trial following adverse events among patients receiving nucleoside analogue treatment.
The Recover study recruited 1350 Spanish patients who discontinued a nucleoside analogue due to an adverse event. 48% of patients were on their fourth HAART regimen and three quarters had taken at least three different regimens, so the frequency of lipid disturbances in this highly treatment-experienced population was high. However, the main reason for discontinuing a drug was lipoatrophy (58% of all switches were attributed to this problem), with peripheral neuropathy the second most common cause (13%). The drug most commonly discontinued was d4T (by 65% of all patients).
Although only 3% of patients were switched due to hypertriglyceridemia, 13% had elevated triglyceride levels. At baseline the median triglyceride level was 458mg/dl. Amongst those who switched from d4T to tenofovir, the median fall was –105 mg/dl at week 24 (to 353 mg/dl). Although the median value remained above the normal range, 33% of patients reverted to the normal triglyceride range by week 24 (
At baseline 22% of those who switched from d4T to tenofovir had seriously elevated triglyceride levels (>500mg/dl) requiring fibrate treatment. By week 12, 10% of the evaluable patients (132) had triglycerides above this level, and by week 24, 8.3% of the 48 evaluable patients had triglyceride levels that remained above 500mg/dl. However, this analysis did not show what proportion of those with elevated triglycerides had experienced reductions during the follow-up period.
During the follow up period 46% of patients took efavirenz and 31% were taking protease inhibitors that might elevate triglycerides.
The effect of a switch from d4T to tenofovir on total cholesterol was less clearcut. Total cholesterol fell from 266mg/dl to 231mg/dl at week 12, a reduction of 35mg/dl, but patients who switched to tenofovir had total cholesterol levels only 18mg/dl lower than baseline after six months of follow-up. However, that result remained statistically significant (p=0.03).
Observed improvements in lipoatrophy occurred in 10.8% of patients, but changes in lipoatrophy could only be judged subjectively by doctor and patient. The vast majority of patients did not experience improvements after six months, suggesting that longer follow-up will be needed if this switch does have a beneficial effect. An Australian study of switching from d4T to abacavir found no visually detectable difference a year after switching, but discernable improvement after two to three years. A randomised study looking at switching from d4T to abacavir or tenofovir is currently following patients and is expected to report 48 week results towards the end of 2004.
A poster presentation from the study also showed that the majority of treatment switches occurred in patients receiving d4T treatment. 66% of NRTI discontinuations occurred in d4T-treated patients, followed by ddI (13%), AZT (13%), abacavir (6%) and 3TC (3%).
Domingo P et al. Dyslipidemia improvement in patients switching from d4T to tenofovir (Recover study). Ninth European AIDS Conference, Warsaw, abstract F8/5, 2003.
Palacios R et al. Identification of NRTI treatment limiting toxicities and drugs involved. Ninth European AIDS Conference, Warsaw, abstract poster 9 1/4, 2003.