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Dyslipidemia Improvement After Switch From d4T to Tenofovir
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Reported by Jules Levin
D4T and tenofovir were compared in Study 903 where patients also received 3TC plus efavirenz. Study investigators compared d4T and TDF with regards to the development of elevated lipids and had the following findings.
2% of patients taking tenofovir regimen developed grade 3/4 triglycerides elevations vs 11% in the d4T group. There was little triglyceride elevation on tenofovir but the average increase of triglycerides was 100 mg/dL on the d4T regimen.
Total cholesterol increased about 50 mg/dl for the d4T group and 30 mg/dL for the tenofovir group. LDL (bad) cholesterol, increased about 20 mg/dL for the d4T group vs about 10 mg/dL for the tenofovir group. These differences were signifi-cant. Patients taking the d4T regimen were more likely to use lipid-lowering drugs (10% vs 2%). Peripheral neuropathy occurred for 10% of patients on the d4T regimen vs 3% for patients on the tenofovir regimen.
At ICAAC a Spanish research group (Moreno and colleagues, abst. H-855b) presented in a late breaker poster changes in lipids from a study of patients who switched from a d4T based regimen to TDF. Study was conducted in association with Gilead. The study has been ongoing since Sept 2002 and it is prospective and multicenter. The stated objective of the study was to evaluate the strategy of managing NRTI treatment toxicities by switching NRTI to tenofovir in virologically suppressed patients. They included 1350 heavily pretreated patients who substituted tenofovir for a NRTI they were currently taking due to reported adverse events. 65% of patients were taking d4T, 13% ddI, 13% AZT, 6% abacavir, 2% 3TC, and 1% ddC. No other drug substitution was concomitantly allowed along with TDF. The The study is ongoing in 120 Spanish centers and follow-up to 48 weeks is scheduled.
70% of study participants are men. Half of them have been IVDUs. The mean CD4 count prior to switching to TDF was 529 cells. 72% of patients were on their 3rd ART regimen or more. Lipodystrophy and peripheral neuropathy have been the 2 major causes for NRTI substitution (50% and 13%, respectively). D4T was the most frequently switched drug (n=886, 65%). Two of the main causes for d4T substitution by TDF were hypertriglyceridemia (271 patients), and hypercholesterolemia (193 patients). The researchers did not report the other ART drugs patients were taking in their regimen. A third of the patients have reached 12 weeks of follow-up after TDF therapy was initiated. For some patients the overall median time on previous treatment with d4T was 4 years (2-5 years).
Results show that triglycerides (n=94) dropped from a mean of 458 mg/dl on the prior NRTI to 278 mg/dl on TDF at 12 weeks (95% CI 254.98 – 278.48). 20% of the patients saw their triglyceride levels return to normal values (p<0.001). Cholesterol levels (n=70) dropped from a mean of 265 mg/dl to a mean of 230 mg/dl (95% CI 220.26 – 241.66) at 12 weeks (p<0.001). No virologic rebound was seen after switching nor was any significant change in CD4 count seen.
The study did not report on NRTI mutations patients may have had which might effect virologic suppression in the longer term. For example, if patients had K65R, the TDF mutation, along with reduced susceptibility to TDF this should be considered. It may be important to consider the capacity of the full regimen to maintain viral suppression. The study did not explore the strategy switching from d4T to abacavir and saving TDF for the future.
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