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Switch From TDF to TAF in HIV/HBV+ Maintains Viral Control, Helps Kidneys
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17th European AIDS Conference, November 6-9, 2019, Basel
Mark Mascolini
In 98 HIV/HBV-coinfected people with moderate kidney impairment in the Swiss HIV Cohort Study (SHCS), switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) maintained HIV and HBV control while improving kidney function [1].
In the past decade treatment of HIV/HBV coinfection often incorporated TDF, which improved HBV outcomes compared with lamivudine (3TC) or emtricitabine (FTC) and led to HBV resistance less often. But TDF-related kidney impairment prompted caution in using this nucleotide analog and inspired hope that TAF would control HBV and HIV as well as TDF, but with fewer kidney side effects.
SHCS investigators undertook this study because nothing had been published on using TAF for people with HIV/HBV coinfection and renal disease. In such people trading TDF for TAF, they aimed to evaluate (1) HIV and HBV suppression, (2) changes in kidney function assessed by estimated glomerular filtration rate (eGFR) and proteinuria, and (3) changes in alanine aminotransferase (ALT).
The analysis included all data from 2 years before through 1 year after the switch to TAF. Participation in this study required an HIV load below 50 copies, an eGFR between 30 and 89 mL/min, and TAF maintained until the end of the observation period, August 2019. The Swiss team defined HBV infection as a positive hepatitis B surface antigen (HBsAg) before the TDF-to-TAF switch.
Among 515 HIV/HBV coinfected people in the SHCS, 98 met study entry criteria. The study group had a median age of 53 years (interquartile range [IQR] 48 to 58), a median CD4 count of 589 (IQR 400 to789), and a median 10.4 years on TDF (IQR 6.8 to 12.7). While 59% of participants were men who have sex with men, 15% were women, 18% were African, 4% had HCV, and 8% had diabetes.
The most frequent antiretrovirals at the TAF switch were dolutegravir (19%), rilpivirine (15%), darunavir (13%), elvitegravir (11%), efavirenz (10%), and nevirapine (7%). Almost half of the study group, 44%, replaced only TDF in their antiretroviral regimen.
In 48 people who had transient elastography at the time of the switch, METAVIR fibrosis score was F0-F1 in 78%, F2 in 7%, F3 in 5%, and F4 in 10%. At the switch point, 97% of participants had HBV DNA below 50 IU/mL, 80% had an eGFR of 60 to 89 mL/min, 20% were at 30 to 59 mL/min, 71% had normal ALT, and 29% had elevated ALT.
One year after the TDF-to-TAF switch, 80 of 81 people (99%) maintained an HIV load below 50 copies (1 person had poor antiretroviral adherence), 52 of 55 had an HBV load below 50 IU/mL (1 had poor adherence, 1 was not suppressed at baseline, and 1 had an HBV load of 56 IU/mL). Four of 98 people (4%) lost HBsAg positivity.
In 78 people with a baseline eGFR of 60 to 89 mL/min, eGFR slope slipped 2.2 mL/min in the 12 months before the switch and inched up 1.7 mL/min in the 12 months after the switch in an analysis adjusted for age, sex, ethnicity, diabetes, and time-updated use of dolutegravir, cobicistat, and cotrimoxazole. In 20 people with a baseline eGFR of 30 to 59 mL/min, eGFR slope waned 5.8 mL/min in the 12 months before the swap and rebounded 11.9 mL/min in the 12 months afterwards. Slope differences were 3.9 before the switch (P = 0.0278) and 17.7 after the switch (P < 0.001).
Protein-to-creatinine ratio (adjusted for baseline eGFR, age, sex, ethnicity, diabetes, and arterial hypertension) rose 1.3 mg/mmol per year on TDF and fell 9.4 mg/mmol per year after TAF began. The TDF-to-TAF difference measured 10.7 mg/mmol (95% confidence interval 5.1 to 16.3).
Among 69 people with a normal baseline ALT, the ALT slope dropped 1.1 IU/L in the last 12 months on TDF and rose 5.9 IU/L in the first 12 months of TAF in an analysis adjusted for age, sex, transmission risk, HCV infection, and HBV replication at the switch and time-updated AUDIT-C score (which identifies hazardous drinkers), body mass index, and efavirenz use. In 29 people with elevated ALT at baseline, the ALT slope rose 5.9 IU/L in the last 12 months of TDF and dropped 17.7 IU/L in the first 12 months of TAF. The slope difference was 7 (P = 0.0288) in people with a normal baseline ALT and -23.6 (P < 0.001) in people with elevated baseline ALT.
The SHCS investigators concluded that "in HIV/HBV coinfected patients with moderate renal impairment, replacing TDF by TAF was associated with improvements in renal function and ALT decline, with maintenance of HIV and HBV viral suppression."
Reference
1. Surial B, Beguelin C, Stockle M, et al. Outcomes after switching from TDF to TAF in HIV/HBV-coinfected individuals with renal impairment: a nationwide cohort study. 17th European AIDS Conference, November 6-9, 2019, Basel. Abstract 12/5.
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