A new coformulation of elvitegravir/cobicistat/emtricitabine/tenofovir (Stribild) containing tenofovir alafenamide (TAF) -- an improved prodrug of tenofovir -- offered better bone and kidney safety, while maintaining viral suppression, in patients who switched from efavirenz/tenofovir/emtricitabine (Atripla), according to a study presented at ICAAC/ICC 2015 in San Diego.
The study, which was presented by David Shamblaw, M.D., followed 376 individuals living with HIV (median age of 39) who had achieved undetectable viral loads while taking efavirenz/tenofovir/emtricitabine. Of these participants, 251 were switched to elvitegravir/cobicistat/emtricitabine/TAF (E/C/F/TAF) and 125 remained on efavirenz/tenofovir/emtricitabine.
After 48 weeks, 96% of the TAF group and 90% of the efavirenz group maintained an undetectable viral load. In terms of bone safety, those in the TAF group had an average change of +1.44% in hip bone mineral density (BMD), compared to -0.24% in the efavirenz group (P < .001). Moreover, the average change in spine BMD was +0.86% for the TAF group and -0.22% for the efavirenz group (P = .048).
In terms of kidney safety, levels of proteinuria and specific proximal tubular proteinuria (indicators of kidney damage) were significantly lower in those in the TAF group than those in the efavirenz group.
|Median Percentage Change at Week 48||TAF Group||Efavirenz Group||Significance|
|Urine Protein: Creatinine||-13.8||+7.2||P < .001|
|Urine Albumin: Creatinine||-16.3||+5.4||P < .001|
|Retinol Binding Protein: Creatinine||-22.5||+24.4||P < .001|
|Beta-2-Microglobulin: Creatinine||-42.7||+18.9||P < .001|
The participants were also assessed for central nervous system (CNS) side effects, including dizziness, insomnia, impaired concentration, somnolence and abnormal dreams. At week two, those in the TAF group reported a reduction of 58% while those in the efavirenz group reported a reduction of 5%, according to Shamblaw.
Additionally, a second study examined E/C/F/TAF in patients with an estimated glomerular filtration rate (eGFR) between 30-69 mL/min. Glomerular filtration rate is a measure of how well your kidneys filter out waste products, with a number below 60 signifying kidney damage. The study followed 80 patients who had achieved undetectable viral loads, who were then switched to E/C/F/TAF. After 48 weeks, they maintained a stable eGFR and saw significant reduction in levels of proteinuria. These results suggest that E/C/F/TAF could be a safe option for patients who have impaired kidney function.
The U.S. Food and Drug Administration will decide on the new coformulation of E/C/F/TAF by early November 2015.