Objective. To evaluate the effect of changing from tenofovir disoproxil fumarate (TDF) –containing antiretroviral therapy (ART) to tenofovir alafenamide (TAF) –containing ART in patients ages 60 years and older living with HIV.
Design. Prospective, open-label, multicenter, randomized controlled trial.
Setting and participants. The study was completed across 36 European centers over 48 weeks. Patients were enrolled from December 12, 2015, to March 21, 2018, and were eligible to participate if they were diagnosed with HIV-1; virologically suppressed to < 50 copies/mL; on a TDF-containing ART regimen; and ≥ 60 years of age.
Intervention. Participants (n = 167) were randomly assigned in a 2:1 ratio to ART with TAF (10 mg), elvitegravir (EVG; 150 mg), cobicistat (COB; 150 mg), and emtricitabine (FTC; 200 mg) or to continued therapy with a TDF-containing ART regimen (300 mg TDF).
Main outcome measures. Primary outcome measures were the change in spine and hip bone mineral density from baseline at week 48. Secondary outcome measures included bone mineral density changes from baseline at week 24, HIV viral suppression and change in CD4 count at weeks 24 and 48, and the assessment of safety and tolerability of each ART regimen until week 48.
Main results. At 48 weeks, patients (n = 111) in the TAF+EVG+COB+FTC group had a mean 2.24% (SD, 3.27) increase in spine bone mineral density, while those in the TDF-containing group (n = 56) had a mean 0.10% decrease (SD, 3.39), a difference of 2.43% (95% confidence interval [CI], 1.34-3.52; P < 0.0001). In addition, at 48 weeks patients in the TAF+EVG+COB+FTC group had a mean 1.33% increase (SD, 2.20) in hip bone mineral density, as compared with a mean 0.73% decrease (SD, 3.21) in the TDF-containing group, a difference of 2.04% (95% CI, 1.17-2.90; P < 0.0001).
Similar results were seen in spine and hip bone mineral density in the TAF+EVG+COB+FTC group at week 24, with increases of 1.75% (P = 0.00080) and 1.35% (P = 0.00040), respectively. Both treatment groups maintained high virologic suppression. The TAF+EVG+COB+FTC group maintained 94.5% virologic suppression at week 24 and 93.6% at week 48, as compared with virologic suppression of 100% and 94.5% at weeks 24 and 48, respectively, in the TDF-containing group. However, the TAF+EVG+COB+FTC group had an increase in CD4 count from baseline (56 cells/µL), with no real change in the TDF-containing group (–1 cell/µL). Patients in the TAF+EVG+COB+FTC group had a mean 27.8 mg/g decrease in urine albumin-to-creatinine ratio (UACR) versus a 7.7 mg/g decrease in the TDF-containing group (P = 0.0042). In addition, patients in the TAF+EVG+COB+FTC group had a mean 49.8 mg/g decrease in urine protein-to-creatinine ratio (UPCR) versus a 3.8 mg/g decrease in the TDF-containing group (P = 0.0042).