For the past few years, studies have increasingly highlighted the contribution of at least some of the nucleosides to increases in lipids, such as total cholesterol and triglycerides. Most recently, the Gilead 903 study comparing tenofovir (TDF, Viread) to d4T (stavudine, Zerit) when paired with 3TC (lamivudine, Epivir) and efavirenz (EFV, Sustiva) showed that there were higher levels of these lipid fractions in patients taking d4T versus those on tenofovir. This, and other data, led to the current study, presented here. The investigator group in Spain chose to substitute tenofovir for one of the nucleosides in a large number of patients, studying both the ability of tenofovir to maintain viral suppression as well as changes in the lipid measurements.

The investigators report that 1,350 patients on NRTI-based regimens had this substitution done. Most (65 percent) were on d4T. The others were on primarily ddI (didanosine, Videx) and AZT (zidovudine, Retrovir). They reported results from those who made this switch -- which, for the majority of people, was done for either reasons of lipodystrophy or peripheral neuropathy. However, substitutions were also made due to lipid abnormalities and this was the focus of their results. They reported that the triglycerides for 94 people dropped from 458 to 278 mg/dL 12 weeks later -- a highly statistically significant drop (p<.001). Twenty percent actually normalized their triglycerides. Cholesterol results were reported on 70 people, and dropped from a mean of 265 to 231 -- also a highly significant result (p<.001). There were no patients who had virologic rebound as a result of the substitution to tenofovir, although the length of follow-up for this conclusion was not reported.

These results support the studies done in antiviral-naive patients which show that tenofovir is often just as potent as other commonly selected NRTIs and has some safety advantages as shown here with regards to improved lipid fractions.

There are some limitations to these data, in that there were no fractions of HDL or LDL shown. However, prior data on tenofovir would suggest that these would change favorably when using this agent. While many patients made the change to tenofovir because they experienced lipodystrophy on their current regimen, there were no data yet available to show how reversible this side effect is as a result of this substitution.

In addition, it is certainly possible that at least some patients could theoretically experience viral rebound with this switch, as there are some mutations that might confer more resistance to tenofovir than to other drugs -- for example, a K65R mutation confers significant resistance to tenofovir, but none to AZT.

Nevertheless, these data reassure us that many, if not most, patients who confront toxicity while on their current NRTIs will be able to maintain viral control and address at least some of the current toxicity concerns by using tenofovir as a replacement antiviral.