Brief Report: Weight Gain in Persons With HIV Switched From Efavirenz-Based to Integrase Strand Transfer Inhibitor–Based Regimens

Abstract

Background With the introduction of integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART), persons living with HIV have a potent new treatment option. Recently, providers at our large treatment clinic noted weight gain in several patients switched from efavirenz/tenofovir disoproxil fumarate/emtricitabine (EFV/TDF/FTC) to dolutegravir/abacavir/lamivudine (DTG/ABC/3TC). In this study, we evaluated weight change in patients with sustained virologic suppression switched from EFV/TDF/FTC to an INSTI-containing regimen. Methods We performed a retrospective observational cohort study among adults on EFV/TDF/FTC for at least two years who had virologic suppression. We assessed weight change over 18 months in patients who switched from EFV/TDF/FTC to an INSTI-containing regimen or a protease inhibitor (PI)-containing regimen versus those on EFV/TDF/FTC over the same period. In a sub-group analysis, we compared patients switched to DTG/ABC/3TC versus raltegravir- or elvitegravir-containing regimens. Results A total of 495 patients were included: 136 switched from EVF/TDF/FTC to an INSTI-containing regimen and 34 switched to a PI-containing regimen. Patients switched to an INSTI-containing regimen gained an average of 2.9 kg at 18 months compared to 0.9 kg among those continued on EFV/TDF/FTC (p=0.003), while those switched to a PI regimen gained 0.7 kg (p=0.81). Among INSTI regimens, those switched to DTG/ABC/3TC gained the most weight at 18 months (5.3 kg, p=0.001 compared to EFV/TDF/FTC). Conclusion Adults living with HIV with viral suppression gained significantly more weight after switching from daily, fixed dose EFV/TDF/FTC to an INSTI-based regimen compared to those remaining on EFV/TDF/FTC. This weight gain was greatest among patients switching to DTG/ABC/3TC.

A retrospective analysis of weight changes in HIV-positive patients switching from a tenofovir disoproxil fumarate (TDF)- to a tenofovir alafenamide fumarate (TAF)-containing treatment regimen in one German university hospital in 2015–2017

“…Retrospective cohort studies carried out in Brazil, the USA and France support the notion that antiretroviral therapies, especially strand transfer inhibitor-based regimens, are associated with weight increase [13][14][15]; there are, however, no published data on weight changes associated with backbone switching from a TDF-to TAF-based regimen. Unstructured, unpublished clinical observations (personal communications by colleagues/patients) indicate a potential weight gain in patients following a switch from TDF-to TAF-containing regimens.…”

Adipocytes impair efficacy of antiretroviral therapy

“…Expression of drug transporters by adipocytes and drug-drug interactions also likely influence ART penetration into AT. It will be important to understand how the selective penetration of these agents into AT is associated with viral persistence in AT, as well as the fat accumulation, weight gain and obesity observed in ART-treated, HIV-infected patients (Crum-Cianflone et al, 2010; Guehi et al, 2016; Koethe et al, 2016; Menard et al, 2017; Norwood et al, 2017). …”

Specific Biological Features of Adipose Tissue, and Their Impact on HIV Persistence

“…Works are still ongoing notably to decipher the respective impact of the local viral infection and antiretroviral treatment. The question is even more relevant with the recent description of weight gain in patients (and notably women) treated with integrase inhibitors (Norwood et al, 2017;Bourgi et al, 2019;Kerchberger et al, 2019). However, more recent data suggest an even broader impact of fat tissue infection, potentially affecting systemic secondary immune responses and contributing to the accelerated aging, two defects commonly associated with chronic HIV infection.…”