December 15, 2006

Long-Term Data on Combivir vs. Viread/Emtriva
(AIDSmeds.com)

Researchers have published extended follow-up data from an important clinical trial comparing two pairs of nucleoside reverse transcriptase inhibitors (NRTIs), both combined with Sustiva® (efavirenz): twice-daily Combivir® (zidovudine plus lamivudine) vs. once-daily Viread® (tenofovir) plus Emtriva® (emtricitabine). The 96-week data from Gilead Science's Study 934, published in the December 15 issue of the Journal of Acquired Immune Deficiency Syndromes, suggests comparable long-term viral load benefits between the two regimens and favorable CD4 (T4 cell) count and side effect results for Viread/Emtriva.

More than ten years after the introduction of combination drug treatment for HIV, we know that piecing together a safe and effective regimen requires doctors and patients to choose their meds carefully. Fortunately, much research has been done to help guide this selection process. Most studies have investigated key differences among the protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). To control HIV, however, PIs or NNRTIs need to be matched up with a "backbone" of other drugs – usually two NRTIs.

Until recently, it was generally believed that the NRTIs were more alike than different. As a result, experts thought it safe to say that any two would do. But we now know that there are differences between NRTI options and that studies are needed to help guide their selection. In turn, results from clinical trials like Gilead Science's Study 934, comparing the dual NRTI-combo Combivir to Viread/Emtriva, have been watched closely.

Viread and Emtriva are often prescribed together as the once-daily fixed-dose combination tablet Truvada®, which became commercially available after Study 934 began. Atripla™, a fixed-dose combination tablet containing Sustiva, Viread, and Emtriva, is also available.

Study 934 enrolled 517 HIV positive people starting HIV treatment for the first time. The 48-week data from the study – published earlier this year in the New England Journal of Medicine – found that 80% of people in the Viread/Emtriva group had viral loads below 50 (undetectable), compared with 70% in the Combivir group.

After 96 weeks of treatment, 67% of patients in the Viread/Emtriva group, compared to 61% of patients in the Combivir group, maintained viral loads below 50. The viral load difference between the two groups was not statistically significant, meaning that it could have been due to chance.

Patients in the Viread/Emtriva group experienced greater CD4 cell increases (a gain of 270 cells) after 96 weeks, compared to those in the Combivir group (a gain of 237 cells). This difference was statistically significant.

There was also a significant difference between the two groups in terms of viral load rebounds after 96 weeks (defined as having a confirmed viral load of greater than 400 after achieving confirmed viral load of less than 400). Five percent of patients in the Combivir group experienced rebound, compared to less than 1% of Viread/Emtriva patients.

The study authors also reported that, after 96 weeks of treatment, discontinuation of study medications due to side effects was significantly higher among Combivir patients (11%) compared to those receiving Viread/Emtriva (5%). The most common side-effect related reasons for discontinuing treatment were anemia (6% in the Combivir group vs. 0% in the Viread/Emtriva group), fatigue (2% vs. 0%, respectively), nausea (2% vs. 1%, respectively), and rash (less than 1% vs. 2%, respectively).

Study 934 also measured limb fat – the amount of fat in the legs – using DEXA scanning in some patients in both groups. The researchers included this measurement to determine if either regimen increases the risk of lipoatrophy (a decrease in subcutaneous fat in the legs, arms, or face).

Patients in the Viread/Emtriva group had significantly more limb fat (7.7 kg) at week 96 compared to patients in the Combivir group (5.5 kg). Since the beginning of the study, patients in the Combivir group experienced an average limb fat decrease of 0.7 kg, compared to a 0.3 kg increase in the Viread/Emtriva group. While these differences were statistically significant, the researchers did not conclude that lipoatrophy was necessarily more common, or the risk for lipoatrophy higher, in the Combivir group compared to the Viread/Emtriva group.

Study 934 will continue following patients for a total of 144 weeks.