- The pooled data from 26 treatment naïve and antiretroviral switch clinical studies demonstrated the renal safety of tenofovir alafenamide (TAF) over tenofovir disoproxil fumarate (TDF) in children and adults living with HIV.
- There were no cases of proximal renal tubulopathy (PRT) and significantly fewer discontinuations due to renal adverse events (AEs) in the TAF group compared with the TDF group.
- Patients on TAF-containing regimens showed favourable changes in renal biomarkers compared to those taking TDF.
TDF is highly efficacious and generally well tolerated but may cause renal AEs. In contrast, TAF has been associated with improvement in markers of renal dysfunction, although low rates of renal events were seen in individual trials. In order to compare the differences in clinically significant renal outcomes between TAF and TDF-containing regimens, the authors conducted a large integrated analysis.
The analysis included 26 phase 2 and 3 multicentre, multinational, clinical trials of TAF-containing regimens in persons living with HIV (adults and children aged ≥6 years) who were either treatment naïve or virologically suppressed on a stable antiretroviral therapy regimen containing TDF.
Primary renal safety outcomes were measured as the incidence of PRT events and study drug renal discontinuation events.
Secondary outcomes (based on 7 large randomized studies: 2 treatment-naïve and 5 switch studies) were; incidence of renal AEs, treatment-emergent proteinuria, changes in serum creatinine (SCr), creatinine clearance (CrCl) and urinary biomarkers (albumin, beta-2-microglobulin, and retinol binding protein to creatinine ratios (UACR, β2M:Cr and RBP:Cr).
Pooled data included exposure of 12,519 person-years to TAF and 5,947 person-years to TDF.
Participants (n=9,322, median age 42 years, 21% women, 27% black race) either initiated or switched to regimens containing TAF (n=6,360) or initiated or continued on regimens containing TDF (n=2,962).
There were no cases of PRT or Fanconi syndrome in participants receiving TAF versus 10 cases in those receiving TDF (p
The 0.05% of individuals on TAF (3/6360) versus the 0.47% on TDF (14/2962) (p
Participants initiating TAF- versus TDF-based regimens had more favourable changes in renal biomarkers through 96 weeks of therapy. There were favourable changes in CrCl and in proximal tubule function (β2M:Cr and RBP:Cr) and a lower incidence of treatment-emergent proteinuria in participants taking TAF-containing regimens.
Limitations: the number of PRT cases were probably underestimated; participants may have been healthier than the general population of HIV patients; individual-level data on the duration of prior TDF therapy were not available.