Tenofovir / FTC 'non-inferior' to Combivir after one year, Gilead study shows (corrected)

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This is a corrected version of an article originally published on 3 February 2005.

Gilead Sciences announced preliminary 48-week results of its Study 934 today, showing that the combination of its nucleotide analogue tenofovir (Viread) and nucleoside analogue FTC (emtricitabine, Emtriva) is not inferior to Combivir, GlaxoSmithKline's combination of the nucleoside analogues AZT (zidovudine) and 3TC (lamivudine). Both combinations were given along with efavirenz (Sustiva).

Study 934 is a multicentre, open-label phase III trial that enrolled 517 treatment-naïve HIV-positive patients with viral loads above 10,000 copies/ml. Patients received 600mg efavirenz once daily with either 300mg tenofovir and 200mg FTC, both taken once daily, or Combivir twice daily (300mg AZT and 150mg 3TC). Although the total length of study will be 96 weeks, its primary endpoint is at 48 weeks.

Glossary

nucleoside

A precursor to a building block of DNA or RNA. Nucleosides must be chemically changed into nucleotides before they can be used to make DNA or RNA. 

first-line therapy

The regimen used when starting treatment for the first time.

tolerability

Term used to indicate how well a particular drug is tolerated when taken by people at the usual dosage. Good tolerability means that drug side-effects do not cause people to stop using the drug.

phase III

The third and most definitive stage in the clinical evaluation of a new drug or intervention, typically a randomised control trial with the new intervention compared to an existing therapy or a placebo, in large numbers of participants (typically hundreds or thousands). Trial results are used to evaluate the overall risks and benefits of the drug and provide the information needed for regulatory approval.

nucleotide

A building block of DNA or RNA, chemical structures that store genetic information. 

In an intent-to-treat analysis consisting of 487 patients, the study found that significantly more patients in the tenofovir / FTC arm had viral loads below 400 copies/ml (84 vs. 73%, p = 0.002) using the 'time to loss of virologic response' algorithm. Significantly more patients in this arm also had viral loads below 50 copies/ml (80 vs. 71%, p = 0.027).

The patients receiving tenofovir / FTC also had greater increases in CD4 cell count (189 vs. 158 cells/mm3, p = 0.002).

This group also experienced fewer side-effects requiring discontinuation of the study drugs (4 vs. 9% of patients, p = 0.019). The commonest side-effects were anaemia (0 vs. 6%), nausea (1 vs. 2%), vomiting (0 vs. 1%) and fatigue (0 vs. 1%). In a previous presentation of interim data from this study, the better tolerability of tenofovir / FTC and lower drop-out rate were identified as the major cause for the apparent difference in the combinations' performances.

Although these findings suggest that tenofovir / FTC has a superior effect to Combivir, the design of the study only allows the researchers to conclude that their combination is 'non-inferior'.

Gilead Sciences plans to present these 48-week data at a scientific conference later this year.

The company’s fixed-dose combination of tenofovir and FTC, called Truvada, received accelerated marketing approval in the United States in August 2004. Its European marketing approval is expected within the next few months. Today’s published data suggest that Truvada will be an attractive choice for first-line therapy in HIV infection in combination with at least one other antiretroviral drug.

However, it is likely to face strong competition from GlaxoSmithKline’s Kivexa, a once daily combination of abacavir and 3TC recently approved in Europe. The two products have not been compared head-to-head in a clinical trial.