A large pooled analysis of data from more than two dozen studies has found that Gilead Sciences’ updated version of tenofovir is associated with various kidney-related safety benefits compared with the older version of the antiretroviral.
Various studies have indicated that Gilead’s tenofovir alafenamide (TAF) offers such safety benefits over its older drug tenofovir disoproxil fumarate (TDF). TDF is sold alone as Viread and is part of the Truvada (tenofovir disoproxil fumarate/emtricitabine) combination pill, while TAF is not used alone for HIV but is included in several combination tablets, including Descovy (tenofovir alafenamide/emtricitabine).
Dr Samir K Gupta, of the department of medicine at Indiana University School of Medicine in Indianapolis, and colleagues conducted a pooled analysis of 26 Phase II and III studies of people starting HIV treatment for the first time with TAF or who switched from TDF to TAF.
Fourteen of the studies were double blinded and randomized, six were open label and six had a single study arm. Between them they included 9,322 people, including 6,360 who started or switched to TAF-containing regimens and 2,962 who started or continued taking TDF-containing regimens. Participants were exposed to TAF for a cumulative 12,519 years and to TDF for a cumulative 5,947 years.
The median baseline age of study participants was 42 years old – 21% of study members were female, and 27% were Black.
Among all 26 studies, there were no cases of proximal renal tubulopathy (PRT) health events or Fanconi syndrome (each are serious kidney diseases) among those receiving TAF, compared with 10 cases (0.34% of participants) among those receiving TDF. Three (0.05%) of those receiving TAF stopped taking it because of kidney-related adverse health events compared with 14 (0.47%) of those who received TDF.
Those receiving TAF also had favourable outcomes according to changes in kidney-related biomarkers through 96 weeks of treatment.
“These pooled data from 26 studies, with over 12,500 person-years of follow-up in children and adults, support the comparative renal safety of TAF over TDF,” the study authors concluded.
Objective: Compared with tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF) has been associated with improvement in markers of renal dysfunction in individual randomized trials; however, the comparative incidence of clinically significant renal events remains unclear.
Design: We used a pooled data approach to increase the person-years of drug exposure analysed, maximizing our ability to detect differences in clinically significant outcomes.
Methods: We pooled clinical renal safety data across 26 treatment-naive and antiretroviral switch studies to compare the incidence of proximal renal tubulopathy and discontinuation due to renal adverse events between participants taking TAF-containing regimens vs. those taking TDF-containing regimens. We performed secondary analyses from seven large randomized studies (two treatment-naive and five switch studies) to compare incidence of renal adverse events, treatment-emergent proteinuria, changes in serum creatinine, creatinine clearance, and urinary biomarkers (albumin, beta-2-microglobulin, and retinol binding protein-to-creatinine ratios).
Results: Our integrated analysis included 9322 adults and children with HIV (n = 6360 TAF, n = 2962 TDF) with exposure of 12 519 person-years to TAF and 5947 to TDF. There were no cases of proximal renal tubulopathy in participants receiving TAF vs. 10 cases in those receiving TDF (P < 0.001), and fewer individuals on TAF (3/6360) vs. TDF (14/2962) (P < 0.001) discontinued due to a renal adverse event. Participants initiating TAF-based vs. TDF-based regimens had more favourable changes in renal biomarkers through 96 weeks of therapy.
Conclusion: These pooled data from 26 studies, with over 12 500 person-years of follow-up in children and adults, support the comparative renal safety of TAF over TDF.
Gupta SK, Post FA, Arribas JR, Eron JJ Jr, Wohl DA, Clarke AE, Sax PE, Stellbrink HJ, Esser S, Pozniak AL, Podzamczer D, Waters L, Orkin C, Rockstroh JK, Mudrikova T, Negredo E, Elion RA, Guo S, Zhong L, Carter C, Martin H, Brainard D, SenGupta D, Das M