Data from a Gilead Sciences open-label study of tenofovir plus emtricitabine [Truvada] plus efavirenz [Sustiva] and the fixed dose combination product Combivir (lamivudine 150 mg/zidovudine 300 mg) plus efavirenz were recently published in a peer-reviewed clinical journal.

In this trial, known as Study 934, 517 treatment-naïve people with HIV-1 infection were randomized to either tenofovir disoproxil fumarate (TDF) 300 mg plus emtricitabine (FTC) 200 mg once daily or to GlaxoSmithKline’s (GSK) fixed-dose combination Combivir 1 tablet twice a day, each in combination with efavirenz 600 mg once daily (EFV). The study was designed to show non-inferiority of tenofovir/emtricitabine plus efavirenz to Combivir plus efavirenz at 48 weeks. However, it is difficult to draw conclusions regarding comparative safety and efficacy of these regimens from a single, open-label trial.

Given the need for life-long treatment for HIV, availability of long-term safety and efficacy data is important when choosing a regimen. Combivir has a well-described safety and efficacy profile that has been derived from many short-term and long-term studies. In total, Combivir and its components have been evaluated in more than 50 randomized clinical trials involving more than 18,000 patients since 1995.

Results seen with Combivir plus EFV in this trial were positive and reinforce the value of Combivir demonstrated in previous research. The results show that the proportion of patients achieving and maintaining HIV-1 RNA less than 400 copies/mL through 48 weeks was 73 percent with Combivir plus EFV in the intent-to-treat analysis compared to 84 percent with TDF plus FTC plus EFV.

In an intent-to-treat analysis, discontinuations due to adverse events are counted as treatment failures. In this trial, the higher than usual rate of anemia associated with the arm containing Combivir contributed to the difference in treatment failures. The number of virologic failures seen with Combivir was low (9 in the Combivir plus EFV arm, 4 in the TDF and FTC plus EFV arm). Nine percent of patients receiving Combivir plus EFV withdrew from the trial due to adverse events compared to 4 percent of patients receiving TDF and FTC plus EFV.

Given the open label nature of this trial, public release of the 24-week results may have contributed to the higher discontinuation rate seen in the arm containing Combivir.

“We are always interested in learning more about existing treatments for HIV, but we realize the limited value of a single, open-label study to make comparisons among products,” said Mark Shaefer, PharmD., acting vice president for HIV Clinical Research for the Infectious Diseases Medicines Development Center (MDC) at GSK. “Fortunately, Combivir is one of the most studied HIV therapies on the market with a wealth of information available.”

It is not unusual to see slightly different rates for certain outcomes across clinical trials. In this study, six percent of patients in the Combivir plus EFV arm experienced anemia leading to discontinuation. However, this is higher than typical clinical experience. Protocol definitions of anemia, baseline hemoglobin and hematocrit levels and chance can all influence the results. The prescribing information for Combivir reports a 2.9 percent incidence of anemia. Combivir is a preferred NRTI backbone in the DHHS guidelines for the treatment of therapy-naïve patients. One out of five people currently taking antiretrovirals in the U.S. is taking Combivir. It is the most studied and most widely prescribed dual nucleoside combination product to date.

01/20/06

Source
GlaxoSmithKline. GlaxoSmithKline Perspective on Data Involving Combivir Published in New England Journal of Medicine. Press Release. January 18, 2006.

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