1. A significantly higher percentage of patients taking tenofovir, emtricitabine, and efavirenz had HIV viral load <50 copies/mL than those taking zidovudine, lamivudine, and efavirenz
2. Significantly more patients discontinued medication in the zidovudine-lamivudine group due to adverse events than in the tenofovir-emtricitabine group
Original Date of Publication: January 19, 2006
Study Rundown: Highly-active antiretroviral therapy (HAART) has significantly changed the clinical management and outcomes of HIV patients across the world. Prior to this study, zidovudine or tenofovir coupled with either lamivudine or emtricitabine, and efavirenz were the recommended HAART regimens. This 2006 paper took ART-naïve and otherwise healthy HIV patients and randomly assigned them to either the tenofovir-emtricitabine regimen or the zidovudine-lamivudine regimen for 48 weeks and recorded the effects on viral load as well as adverse effects. In summary, they found that a significantly higher proportion of patients in the tenofovir-emtricitabine group achieved a viral load <50 copes/mL than their counterparts in the zidovudine-lamivudine group (80% vs. 70%, 95%CI 2.0-17.0%, P=0.02). More patients in the zidovudine-lamivudine group discontinued therapy due adverse effects, the most common being marked anemia. While the study was open-label, their primary and secondary objectives were all objective data, which reduces the impact of potential observer bias.
Relevant Reading (903 study): Efficacy and safety of tenofovir DF vs stavudine in combination therapy in antiretroviral-naïve patients
Study Author, Dr. Joel Gallant, MD, MPH, talks to 2 Minute Medicine: Johns Hopkins University, Division of Infectious Disease.
“[This] 934 paper was definitely an important study in the history of antiretroviral therapy. For the first time, it demonstrated that AZT [zidovudine], which had been a cornerstone of treatment since the mid-1980’s, was less effective and more toxic than a comparator, in this case tenofovir.
The paper led to a change in treatment guidelines, which initially demoted AZT to the “alternative” category. Now it’s not even an alternative. The 903 and 934 studies signaled the end of an era in which toxicities like neuropathy, anemia, fatigue, and the dreaded lipoatrophy were virtually inevitable consequences of HIV therapy. Subsequent drug development led us to where we are today, with the majority of patients being treated with simple, well-tolerated, and highly effective regimens, usually given once a day, often with a single pill.”
In-Depth [randomized, controlled study]: This 2006 study published in NEJM was a multicenter, open-label, randomized controlled trial that assigned 500 patients with HIV to either the standard ART regimen of zidovudine, lamivudine, and efavirenz or to the newer drugs tenofovir, emtricitabine, and efavirenz for 48 weeks. All patients had been diagnosed with HIV and had never taken anti-viral therapy in the past. None of the participants had any other significant lab abnormalities. There was no cutoff CD4 count. Patients were followed for 48 weeks and viral load, CD4 count, standard labs, and adverse events were recorded. The primary outcome was reaching a viral load of equal or fewer than 400 copies/mL. The secondary outcomes included HIV RNA levels of less than 50 copies/mL, a positive trend in CD4 count, and the prevalence of adverse events.
The tenofovir-emtricitabine group surpassed the zidovudine-lamivudine group in the primary and all secondary outcomes. It had a significantly higher percentage of patients who achieved HIV RNA levels of less than 400 copies per milliliters (84% vs. 73%, 95%CI 4.0-19.0%, P=0.002) as well as less than 50 copies per milliliters (80% vs. 70%, 95%CI 2.0-17.0%, P=0.02) than those in the zidovudine-lamivudine group. Those patients also had a significant increase in their CD4 cell counts (190 vs. 158 cells; 95%CI 9-55; P=0.002) and fewer significant adverse effects from the drugs. There was also lower incidence of resistance development in the tenofovir-emtricitabine group compared to the zidovudine-lamivudine group.
By Milana Bogorodskaya and Andrew Cheung, M.D.
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