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. 2024 Oct 15;79(4):990-998.
doi: 10.1093/cid/ciae189.

Weight, Anthropometric and Metabolic Changes After Discontinuing Antiretroviral Therapy Containing Tenofovir Alafenamide in People With HIV

José Damas  1 , Aline Munting  1 , Jacques Fellay  2   3 , David Haerry  4 , Catia Marzolini  5   6 , Philip E Tarr  7 , Ana Steffen  8 , Dominique L Braun  9 , Marcel Stoeckle  5 , Enos Bernasconi  10 , Olivier Nawej Tshikung  11 , Christoph A Fux  12 , Katharine E A Darling  1 , Charles Béguelin  13 , Gilles Wandeler  13 , Matthias Cavassini  1 , Bernard Surial  13 ; Swiss HIV Cohort Study (SHCS)
Collaborators, Affiliations

Weight, Anthropometric and Metabolic Changes After Discontinuing Antiretroviral Therapy Containing Tenofovir Alafenamide in People With HIV

José Damas et al. Clin Infect Dis. .

Abstract

Background: Antiretroviral therapy (ART)-related weight gain is of particular concern in people with HIV (PWH). Although weight gain was observed among PWH receiving tenofovir alafenamide (TAF), little is known about the potential reversibility after TAF discontinuation. We evaluated weight and metabolic changes 12 months after TAF discontinuation in the Swiss HIV Cohort Study.

Methods: We included participants who received at least 6 months of TAF-containing ART between January 2016 and March 2023. Using multivariable mixed-effect models, changes in weight and lipid levels were compared between individuals who continued TAF and those who switched to one of the following TAF-free regimens: (1) tenofovir disoproxil fumarate (TDF)-based ART, (2) dolutegravir/lamivudine (DTG/3TC), or (3) long-acting cabotegravir/rilpivirine (CAB/RPV).

Results: Of 6555 participants (median age 54 years, 24.3% female, 13% Black), 5485 (83.7%) continued, and 1070 (16.3%) stopped TAF. Overall, discontinuing TAF was associated with an adjusted mean weight change of -0.54 kg (95% confidence interval [CI] -.98 to -.11) after 12 months. In stratified analyses, switching from TAF to TDF led to an adjusted mean weight decrease of -1.84 kg (95% CI -2.72 to -.97), and to a decrease in mean total cholesterol (-0.44 mmol/L) and triglycerides (-0.38 mmol/L) after 12 months. Switching from TAF-based ART to DTG/3TC (-0.17 kg, 95% CI -.82 to .48) or long-acting CAB/RPV (-0.64 kg, 95% CI -2.16 to .89) did not lead to reductions in weight.

Conclusions: Replacing TAF with TDF in PWH led to a decrease in body weight and an improved lipid profile within 1 year. Weight changes were not observed among individuals who switched to DTG/3TC or long-acting CAB/RPV.

Keywords: HIV; antiretroviral therapy; tenofovir alafenamide; tenofovir disoproxil fumarate; weight.

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Conflict of interest statement

Potential conflicts of interest . P. E. T. received grants, and educational and advisory fees to institution from Gilead, MSD, and ViiV outside the submitted work. O. N. T.’s institution received expenses compensation for expert opinion from ViiV Healthcare. K. E. A. D.'s institution has received research grants from Gilead Sciences and travel grants and lecture fees from Gilead and MSD. B. S. reports support to his institution for travel grants from Gilead Sciences and ViiV healthcare. G. W. reports unrestricted research grants from Gilead Sciences and Roche Diagnostics, as well as travel grants and advisory board/lecture fees from ViiV, Gilead Sciences and MSD, all paid to his institution. M. C.’s institution received research grants and payment for expert testimony from Gilead, MSD, and ViiV. E. B.'s institution received research grants from MSD, consulting fees from Moderna, payment for lectures from Pfizer AG as well as fees for the participation of E. B. to advisory boards and/or travel grants from Gilead Sciences, ViiV, MSD, Abbvie, Pfizer, AstraZeneca, Moderna, and Ely Lilly. C. B. reports participation on the Gilead advisory board on Bulevirtide. K. D. reports grants, payment for lectures, and support for meetings and/or travel from Gilead Sciences, as well as payment for expert testimony from MSD. C. A. F. reports grants from Gilead, as well as Advisory Board attendance support from Gilead, Menarini, Moderna, MSD, and ViiV. M. S. reports support for meetings and/or travel from Gilead, participation on an advisory board for Gilead Sciences, Moderna, MSD, and ViiV Healthcare. O. N. T. reports payment or honoraria for lectures from ViiV Healthcare. C. M. reports speaker honoraria from Gilead, ViiV, and MSD. P. T. reports grants and payment for lectures from Gielad, ViiV, and MSD. D. H. reports grants from Abbvie, AstraZeneka, Gilead, GSK, ViiV, MDF, and Pfizer, consulting fees from AstraZeneca, Gilead, ViiV Healthcare, and Bavarian Nordic, support for travel and/or meetings from Gilead, and payment for leadership or fiduciary role from PFMD and Positive Council. D. L. B. reports payment for lectures, consulting fees,and participation on advisory board from Gilead, ViiV, MSD, Pfizer, and consulting fees from AstraZeneka, support for attending meetings from Gilead. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Graphical Abstract
Graphical Abstract
This graphical abstract is also available at Tidbit: https://tidbitapp.io/tidbits/weight-anthropometric-and-metabolic-changes-after-discontinuing-antiretroviral-therapy-containing-tenofovir-alafenamide-taf-in-people-with-hiv-9af4bba9-2a15-4648-9696-d7c45ea94bcd
Figure 1.
Figure 1.
Weight changes over time after index visit, stratified by the TAF-free ART regimen. Mean changes in weight (line) and corresponding 95% CIs (shaded area) of continuing TAF-based ART (blue line) compared with (A) switching to TDF-based ART, (B) switching to DTG/3TC, (C) switching to LA CAB/RPV, or (D) switching to other ART (red lines). All models were adjusted for age, sex, ethnicity, CD4-cell count, use of integrase inhibitors, physical activity, smoking status, and use of weight-modifying drugs. The model includes random intercepts for each individual. A total of 6282 PWH were included in the analyses. Abbreviations: ART, antiretroviral therapy; CAB/RPV, cabotegravir/rilpivirine; CI, confidence interval; DTG/3TC, dolutegravir/lamivudine; LA, long-acting; PWH, people with human immunodeficiency virus; TAF, tenofovir alafenamide; TDF, tenofovir disoproxil fumarate.
Figure 2.
Figure 2.
Changes in lipid levels 12 m after the index visit, stratified by the TAF-free ART regimen. Mean changes in lipid levels (squares and diamonds) and corresponding 95% CIs (vertical lines) after 12 m of continuing TAF-based ART (diamonds and lines in blue) compared with (A) switching to TDF-based ART, (B) switching to DTG/3TC, (C) switching to LA CAB/RPV, or (D) switching to other ART (squares and lines in red). All models were adjusted for age, sex, ethnicity, individual lipid level at baseline, and time-varying physical activity, weight, and use of lipid-lowering drugs. The model includes random intercepts for each individual. Abbreviations: ART, antiretroviral therapy; CAB/RPV, cabotegravir/rilpivirine; CI, confidence interval; DTG/3TC, dolutegravir/lamivudine; HDL, high-density lipoprotein; LA, long-acting; LDL, low-density lipoprotein; TAF, tenofovir alafenamide; TDF, tenofovir disoproxil fumarate.
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