Individuals who took a year of anti-HIV treatment consisting of efavirenz (Sustiva) with tenofovir and FTC (Truvada) had significantly more limb fat than those who took efavirenz with AZT and 3TC (Combivir), according to results from Gilead Science’s 934 study published in the January 19th edition of the New England Journal if Medicine. Gilead is the manufacturer of Truvada.
The published data also confirmed previously presented preliminary results that showed Truvada with efavirenz was “non-inferior” to a combination consisting of Combivir and efavirenz. To read the aidsmap report of these findings click here.
As well as comparing the efficacy of Truvada and Combivir, the investigators designed a sub-study examining changes in limb fat in 100 patients. Fat loss, or lipoatrophy, is a recognised side-effect of antiretroviral therapy. Once fat loss occurs, it can be difficult or even impossible to reverse.
Drugs from the nucleoside reverse transcriptase inhibitor class, particularly d4T (stavudine, Zerit) have been associated with fat loss. AZT has also been shown to cause fat loss, but at a slower rate than d4T and it is also thought that protease inhibitors may have a role in the side-effect.
Investigators in the 934 study measured changes in limb fat using DEXA scans. On entry to the study, weight was similar in the Truvada and Combivir-treated patients (mean 76kg), however after 48 weeks of treatment, weight had increased by a mean of 2kg in the Truvada-treated patients compared to 1kg in those who received Combivir (a non-significant difference).
However, DEXA scans showed that the 51 patients who received Truvada had significantly more limb fat than the 49 individuals treated with Combivir (9kg vs 7kg, p = 0.03).
Gilead adta on file from the 934 study not included in the New England Journal report suggest that the difference in limb fat becomes more pronounced by week 96. Preliminary analysis of 255 patients who have completed 96 weeks of treatment has shown that these differences in limb fat persist, with median limb fat declining to 5.5kg in the Combivir group and rising to 7.8kg in the Truvada group
Because of concerns about fat loss, the current treatment guidelines of the British HIV Association caution against the use of AZT-containing regimens in both treatment-naïve and treatment-experienced individuals if there are other options available.
The metabolic side-effects of Truvada and Combivir were also compared by the investigators. They found that increases in ‘bad’(LDL) cholesterol were smaller in patients taking Truvada (p Combivir had greater increases in ‘good’ (HDL) cholesterol (p = 0.004). Increases in triglyceride levels were comparable between patients in both treatment arms.
Other side-effects were also examined. A total of 14 patients taking Combivir developed anaemia compared to none of the Truvada-treated individuals (p
There have been concerns that tenofovir can cause kidney problems and the renal function of individuals in the study was closely monitored. No severe kidney abnormalities were seen in patients taking Truvada, although 1% of individuals taking Combivir experienced an increase in their creatinine and phosphorus levels.
Gilead Sciences and Bristol Myers Squibb, the manufacturers of efavirenz, have submitted an application to US regulatory authorities for approval of a pill combining Truvada and efavirenz. This will mean that potent HIV treatment will be possible with just one pill, once a day. Approval is expected to be granted in the summer of 2006.
Gallant JE et al. Tenofovir DF, emtricitabine, and efavirenz vs. zidovudine, lamivudine, efavirenz for HIV. N Engl J Med 354: 251 – 260, 2006.