Switching From TDF to TAF in HIV/HBV-Coinfected Individuals With Renal Dysfunction

A Prospective Cohort Study

Bernard Surial, MD; Charles Béguelin, MD; Jean-Philippe Chave, MD; Marcel Stöckle, MD; Noémie Boillat-Blanco, MD; Thanh Doco-Lecompte, MD; Enos Bernasconi, MD; Jan Fehr, MD; Huldrych F. Günthard, MD; Patrick Schmid, MD; Laura N. Walti, MD; Hansjakob Furrer, MD; Andri Rauch, MD; Gilles Wandeler, MD

Disclosures

J Acquir Immune Defic Syndr. 2020;85(2):227-232.

Conclusions

Switching from TDF to TAF among HIV/HBV-coinfected individuals with renal impairment led to improvements in eGFR, a decline in proteinuria, and to ALT normalization in those with elevated ALT levels. The use of TAF in those individuals seems to be safe and effective, and switching from TDF to TAF should be considered among coinfected individuals with renal impairment or with otherwise unexplained ALT elevations.

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Presented in part at the 17th EACS conference; November 6–9, 2019, Basel, Switzerland.

Acknowledgments
The authors thank all patients, doctors, and nurses associated with the Swiss HIV Cohort Study (SHCS), Alexandra Scherrer and Anna Traytel from the SHCS data center, Danièle Perraudin and Marianne Amstutz from the SHCS coordination center, and especially Daniela Hirter and Christine Brülisauer and Melanie Lacalamita for collecting and maintaining the study data. The members of the SHCS are Anagnostopoulos A, Battegay M, Bernasconi E, Böni J, Braun DL, Bucher HC, Calmy A, Cavassini M, Ciuffi A, Dollenmaier G, Egger M, Elzi L, Fehr J, Fellay J, Furrer H, Fux CA, Günthard HF (President of the SHCS), Haerry D (deputy of "Positive Council"), Hasse B, Hirsch HH, Hoffmann M, Hösli I, Huber M, Kahlert CR (Chairman of the Mother & Child Substudy), Kaiser L, Keiser O, Klimkait T, Kouyos RD, Kovari H, Ledergerber B, Martinetti G, Martinez de Tejada B, Marzolini C, Metzner KJ, Müller N, Nicca D, Paioni P, Pantaleo G, Perreau M, Rauch A (Chairman of the Scientific Board), Rudin C, Scherrer AU (Head of Data Centre), Schmid P, Speck R, Stöckle M (Chairman of the Clinical and Laboratory Committee), Tarr P, Trkola A, Vernazza P, Wandeler G, Weber R, and Yerly S.
The data are gathered by the Five Swiss University Hospitals, two Cantonal Hospitals, 15 affiliated hospitals and 36 private physicians (listed in https://www.shcs.ch/180-health-care-providers).

Table 1. Characteristics of the Study Population at the Time of Switch From TDF to TAF
	eGFR 60–89 mL/min (n = 84)	eGFR Below <60 mL/min (n = 22)	P
Female (%)	13 (15.5)	3 (13.6)	1.00
Median age in years (IQR)	51.5 (48–57)	54.5 (50.3–69.8)	0.02
African origin (%)	17 (20.2)	3 (13.6)	0.69
PWID (%)	4 (4.8)	2 (9.1)	0.60
Median CD4 count (cells/mL)	593 (426–806)	462.5 (274.3–636.3)	0.04
Hepatitis D infection (%)	5 (6.0)	2 (9.1)	0.96
Chronic HCV infection (%)	2 (2.4)	2 (9.1)	0.40
Diabetes (%)	5 (6.0)	3 (13.6)	0.45
Treated for arterial hypertension (%)	23 (27.4)	12 (54.5)	0.03
Median eGFR in mL/min (IQR)	78.2 (71.3–83.8)	53.0 (47.5–55.2)	<0.001
Median urine protein-to-creatinine ratio in mg/mmol (IQR)	11.5 (8.8–18.1)	21.4 (15.9–64.4)	0.01
Urine protein-to-creatinine ratio (%)			0.01
>50 mg/mmol	4 (4.8)	5 (22.7)
Missing	23 (27.4)	5 (22.7)
Median ALT in IU/L (IQR)	27.0 (20.5–38.3)	23.0 (17.0–38.0)	0.23
ALT elevated* (%)	30 (35.7)	6 (27.3)	0.82
Grade 1 (<2.5 ULN, %)	28 (33.3)	6 (27.3)
Grade 2 (≥2.5 to <5 times ULN, %)	1 (1.2)	0
Grade 3 (≥5 to <10 times ULN, %)	1 (1.2)	0
Grade 4 (≥10 times ULN, %)	0	0
Significant fibrosis† (%)	13 (15.5)	1 (4.5)	0.29
Cirrhosis‡ (%)	6 (7.1)	0	0.34
Median time on TDF in years (IQR)	10.2 (6.5–12.2)	11.4 (9.2–14.5)	0.11
Switch from TDF to TAF without changes in other components (%)	48 (57.1)	15 (68.2)	0.49
Third drug before switch (%)			0.27
Dolutegravir	16 (19.0)	6 (27.3)
Rilpivirine	12 (14.3)	6 (27.3)
Darunavir	11 (13.1)	4 (18.2)
Elvitegravir	10 (11.9)	0
Efavirenz	10 (11.9)	1 (4.5)
Others	25 (29.8)	5 (22.7)

HCV, hepatitis C virus; eGFR, estimated glomerular filtration rate; PWID, persons who inject drugs, ULN, upper limit of normal.
*ALT >25 for women and >35 for men, according to recommendations of the American Association for the Study of Liver Diseases (AASLD).
†TE >7.0 kPa or APRI >1.5.
‡TE >11.0 kPa or APRI > 2.0.

Authors and Disclosures

Bernard Surial, MD^a, Charles Béguelin, MD^a, Jean-Philippe Chave, MD^b, Marcel Stöckle, MD^c, Noémie Boillat-Blanco, MD^d, Thanh Doco-Lecompte, MD^e, Enos Bernasconi, MD^f, Jan Fehr, MD^g,h, Huldrych F. Günthard, MD^g,i, Patrick Schmid, MD^j, Laura N. Walti, MD^a, Hansjakob Furrer, MD^a, Andri Rauch, MD^a, Gilles Wandeler, MD^a,k and the Swiss HIV Cohort Study

^aDepartment of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland; ^bDivision of Infectious Diseases, La Source Hospital, Lausanne, Switzerland; ^cDivision of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland; ^dDivision of Infectious Diseases, University Hospital of Lausanne, University of Lausanne, Lausanne, Switzerland; ^eDivision of Infectious Diseases, Geneva University Hospital, University of Geneva, Geneva, Switzerland; ^fDivision of Infectious Diseases, Regional Hospital of Lugano, Lugano, Switzerland; ^gDivision of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland; ^hDepartment of Public and Global Health, Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland; ⁱInstitute of Medical Virology, University of Zurich, Zurich, Switzerland; ^jDivision of Infectious Diseases, Cantonal Hospital of St Gallen, St Gallen, Switzerland; and kInstitute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.

Correspondence to
Gilles Wandeler, MD, Department of Infectious Diseases, Inselspital, Bern University Hospital, 3010 Bern, Switzerland (e-mail: gilles.wandeler@insel.ch).

A.R. and G.W. contributed equally. B.S., C.B., A.R., and G.W. designed the study. B.S. and G.W. prepared the first draft of the manuscript. B.S. performed the statistical analyses. J.-P.C., M.S., N.B.-B., T.D.-L., E.B., J.F., H.F.G., P.S., L.W., and H.F. contributed to the conception of the study, data collection, and revised the manuscript for substantial intellectual content. All authors read and approved the final manuscript.

B.S. reports support to his home institution for travel grants from Gilead. C.B., J.-P.C., and T.D.-L. report no conflict of interest. E.B. reports support to his institution for advisory boards and/or travel grants from Gilead, MSD, ViiV, Abbvie, Sandoz, and Pfizer. J.F. reports no conflict of interest. H.F.G. has received unrestricted research grants from Gilead Sciences; fees for data and safety monitoring board membership from Merck; and consulting/advisory board membership fees from Gilead Sciences, ViiV, Sandoz, and Mepha. P.S. reports no conflict of interest. L.N.W. reports support to her home institution for advisory boards or travel grants from MSD and Gilead Sciences. H.F. received unrestricted educational grant from Abbvie, ViiV, Gilead Sciences, MSD, Janssen, and Sandoz paid to the institution. A.R. reports support to his institution for advisory boards and/or travel grants from Janssen-Cilag, MSD, Gilead Sciences, Abbvie, and Bristol-Myers Squibb, and an unrestricted research grant from Gilead Sciences. All remuneration went to his home institution and not to A.R. personally, and all remuneration was provided outside the submitted work. G.W. reports support to his home institution for advisory boards and/or travel grants from MSD, Gilead Sciences, and Abbvie, and an unrestricted research grant from Gilead Sciences.