Tenofovir Prodrug Effective in HIV-1 Infected Virologically Suppressed Adults
SAN DIEGO, CA—HIV-1 infected virologically suppressed adults who were randomized to switch from elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF) to a once-daily E/C/F/tenofovir alafenamide regimen maintained high virologic control at Week 48 compared with those who remained on E/C/F/TDF, study results presented at IDWeek 2015 have found.
The patients also “had significantly improved hip/spine bone mineral density (BMD), serum creatinine, and had significantly less general proteinuria and specific proximal tubular proteinuria than those remaining on E/C/F/TDF,” noted Melanie Thompson, MD, of the AIDS Research Consortium of Atlanta in Atlanta, Georgia.
Tenofovir alafenamide is a tenofovir prodrug co-formulated into a single tablet regimen containing elvitegravir 150mg/cobicistat 150mg/emtricitabine 200mg/tenofovir alafenamide 10mg (E/C/F/TAF).
The study data comprised a prespecified subanalysis of 459 virologically suppressed (HIV-1 RNA <50 copies/mL) adults on blinded E/C/F/TDF for at least 48 weeks who were randomized 2:1 to take open-label E/C/F/TAF or continue a prior regimen.
Results showed that at Week 48, 98.4% (301/306 patients) of those switched to E/C/F/TAF and 97.4% (149/153) of those continuing E/C/F/TDF had HIV-1 RNA <50c/mL (95% confidence interval [CI]: -1.9%, 3.9%).
One patient in each group discontinued treatment unrelated to an adverse event.
Among patients in the E/C/F/TAF group, BMD and serum creatinine improved significantly compared with those in the E/C/F/TDF group.
Mean change from baseline to Week 48 in BMD at the hip was +1.15 (standard deviation [SD] 2.4) vs. -0.17 (SD 2; P<0.001) in the E/C/F/TAF and E/C/F/TDF groups; BMD at the spine was +1.33 (SD 3.6) vs. -0.50 (SD 3.4; P<0.001), respectively.
Urine protein creatinine was -16.2 in the E/C/F/TAF group and +13.7 in the E/C/F/TDF group (P<0.001); urine albumin creatinine was -17.7 vs. +7.7 (P<0.001), respectively. In the E/C/F/TAF group, retinal binding protein creatinine was -28.6 and beta-2-microglobulin creatinine was -43.3, compared with +27.4 and +20.8 in the E/C/F/TDF group, respectively (P<0.001).
“Quantitative proteinuria and tubular proteinuria were significantly improved for patients switching to E/C/F/TAF compared to those continuing E/C/F/TDF,” Dr. Thompson stated. Serum creatinine mean change from baseline was -0.01mg/dL in the E/C/F/TAF group vs. +0.03mg/dL in the E/C/F/TDF group (P<0.001).
Patients in the E/C/F/TAF group had statistically higher changes from baseline in fasting lipid tests. The total cholesterol: HDL ratio change was E/C/F/TAF, +0.2 and E/C/F/TDF, +0.1 (P=0.48).
“Longer term data are needed to understand the clinical relevance of lipid changes in the TAF arm,” Dr. Thompson concluded.
M. Thompson, Gilead Sciences: Investigator , Research support
Bristol Myers Squibb, Inc.: Investigator , Research support
Geo Vax, Inc: Investigator , Research support
Kowa Research Institute: Investigator , Research support
Pfizer Inc: Investigator , Research support
Janssen/Tibotec Therapeutics: Investigator , Research support
Merck & Co: Investigator , Research support
Tobira Therapeutics: Investigator , Research support
ViiV Healthcare: Investigator , Research support