TY - JOUR
T1 - Weight gain before and after switch from TDF to TAF in a U.S. cohort study
AU - Mallon, Patrick W.G.
AU - Brunet, Laurence
AU - Hsu, Ricky K.
AU - Fusco, Jennifer S.
AU - Mounzer, Karam C.
AU - Prajapati, Girish
AU - Beyer, Andrew P.
AU - Wohlfeiler, Michael B.
AU - Fusco, Gregory P.
N1 - Funding Information:
PWGM’s institution has received research grants from GlaxoSmithKline, Gilead Sciences and Janssen Cilag; PWGM has received speaker honoraria from ViiV Healthcare, Gilead Sciences, Janssen Cilag, BMS. and MSD; and advisory board participation from ViiV Healthcare, Gilead Sciences, Janssen Cilag, BMS and MSD. LB, JSF and GPF are employees of Epividian, Inc. Epividian has had research funded by ViiV Healthcare, Merck & Co., Janssen Pharmaceutica and Gilead Sciences. RKH has received research grants from Gilead Sciences and Janssen, speaker honoraria and advisory boards from ViiV Healthcare, BMS, Merck, Gilead Sciences and Janssen, and advisory board participation with ViiV, Gilead Sciences, Janssen, and Epividian. KCM has received research grants from Gilead Sciences, Merck, Janssen, and GSK/ViiV Healthcare and honoraria for Speakers Bureau and Advisory Boards from Gilead Sciences, Merck, Janssen and GSK/ViiV Healthcare; and advisory board participation with Epividian. APB and GP are employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc, Kenilworth, NJ, USA. MBW has participated in post‐conference advisory boards for the Conference on Retroviruses and Opportunistic Infections (CROI) and International AIDS Conference (IAC) and also serves as a principal investigator on ViiV Healthcare clinical trials but does not receive personal compensation for this work, which goes directly to the AIDS Healthcare Foundation.
Funding Information:
This work was supported by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Publisher Copyright:
© 2021 Merck Sharp & Dohme Corp. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of International AIDS Society.
PY - 2021/4
Y1 - 2021/4
N2 - Introduction: Although weight gain has been reported with the use of integrase strand transfer inhibitors (InSTI), concurrent use of tenofovir alafenamide (TAF) has been implicated in recent studies. This study examined weight changes in people living with HIV (PLWH) who switched from tenofovir disoproxil fumarate (TDF) to TAF, to clarify the relative contribution to weight gain of core agents versus TDF to TAF switch. Methods: Antiretroviral-experienced, virologically suppressed PLWH in the U.S. OPERA cohort were included if they switched from TDF to TAF (5NOV2015-28FEB2019) and either maintained all other antiretrovirals or switched from a non-InSTI to an InSTI. Linear mixed models were used to assess weight changes before/after the switch to TAF (restricted cubic splines on time) and rates of change over time (linear splines on time, based on the shape of the weight change curves). Changes in weight on TDF or TAF were assessed among those who maintained other antiretrovirals (overall, by core class), and those who maintained an InSTI or switched to an InSTI (by core agent). All models were adjusted for age, sex, race, (age-sex, race-sex interactions), BMI, CD4 cell count, endocrine disorders and concurrent medications that could affect weight. Results: A total of 6908 PLWH were included, with 5479 maintaining all other antiretrovirals (boosted protease inhibitor: 746, non-nucleoside reverse transcriptase inhibitor: 1452, InSTI: 3281) and 1429 switching from a non-InSTI to an InSTI (elvitegravir/cobicistat: 1120, dolutegravir: 174, bictegravir: 129). In adjusted models, modest weight gain was observed over time on TDF for most (0.24 to 0.71 kg/year); raltegravir was the exception with weight loss. Switching to TAF was associated with early, pronounced weight gain for all (1.80 to 4.47 kg/year). This effect with TAF switch was observed both in PLWH maintaining other antiretrovirals and those switching to an InSTI, regardless of which InSTI agent was used. Weight gain tended to slow down or plateau approximately nine months after switch to TAF. Conclusions: In this large, diverse U.S. cohort of PLWH, switching from TDF to TAF was associated with pronounced weight gain immediately after switch, regardless of the core class or core agent, suggesting an independent effect of TAF on weight gain.
AB - Introduction: Although weight gain has been reported with the use of integrase strand transfer inhibitors (InSTI), concurrent use of tenofovir alafenamide (TAF) has been implicated in recent studies. This study examined weight changes in people living with HIV (PLWH) who switched from tenofovir disoproxil fumarate (TDF) to TAF, to clarify the relative contribution to weight gain of core agents versus TDF to TAF switch. Methods: Antiretroviral-experienced, virologically suppressed PLWH in the U.S. OPERA cohort were included if they switched from TDF to TAF (5NOV2015-28FEB2019) and either maintained all other antiretrovirals or switched from a non-InSTI to an InSTI. Linear mixed models were used to assess weight changes before/after the switch to TAF (restricted cubic splines on time) and rates of change over time (linear splines on time, based on the shape of the weight change curves). Changes in weight on TDF or TAF were assessed among those who maintained other antiretrovirals (overall, by core class), and those who maintained an InSTI or switched to an InSTI (by core agent). All models were adjusted for age, sex, race, (age-sex, race-sex interactions), BMI, CD4 cell count, endocrine disorders and concurrent medications that could affect weight. Results: A total of 6908 PLWH were included, with 5479 maintaining all other antiretrovirals (boosted protease inhibitor: 746, non-nucleoside reverse transcriptase inhibitor: 1452, InSTI: 3281) and 1429 switching from a non-InSTI to an InSTI (elvitegravir/cobicistat: 1120, dolutegravir: 174, bictegravir: 129). In adjusted models, modest weight gain was observed over time on TDF for most (0.24 to 0.71 kg/year); raltegravir was the exception with weight loss. Switching to TAF was associated with early, pronounced weight gain for all (1.80 to 4.47 kg/year). This effect with TAF switch was observed both in PLWH maintaining other antiretrovirals and those switching to an InSTI, regardless of which InSTI agent was used. Weight gain tended to slow down or plateau approximately nine months after switch to TAF. Conclusions: In this large, diverse U.S. cohort of PLWH, switching from TDF to TAF was associated with pronounced weight gain immediately after switch, regardless of the core class or core agent, suggesting an independent effect of TAF on weight gain.
KW - antiretroviral therapy
KW - Cohort
KW - integrase strand transfer inhibitor
KW - tenofovir alafenamide
KW - tenofovir disoproxil fumarate
KW - weight gain
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U2 - 10.1002/jia2.25702
DO - 10.1002/jia2.25702
M3 - Article
C2 - 33838004
AN - SCOPUS:85104218378
VL - 24
JO - Journal of the International AIDS Society
JF - Journal of the International AIDS Society
SN - 1758-2652
IS - 4
M1 - e25702
ER -