Combined tenofovir, lamivudine, and dolutegravir treatment increases leptin and FABP4 expression in human subcutaneous adipose tissue

INTRODUCTION: Several antiretroviral regimens reportedly affect adipose tissue function. While earlier antiretroviral combinations were associated with lipodystrophy, more recent regimens, particularly those containing dolutegravir, have been linked to fat gain. However, the direct impact of contemporary antiretroviral regimens on human adipose tissue remains unclear. OBJECTIVE: Therefore, this study aimed to elucidate the effects of the combination of TDF, 3TC, and DTG on human adipose tissue function in vitro. For comparison, we also analyzed an alternative regimen consisting of AZT, 3TC, and DTG, given the well-documented association of AZT with lipodystrophy. METHODS: Cells from the stromal vascular fraction of both adipose depots were isolated and treated with each antiretroviral combination for 72 hours. Additionally, adipose tissue explants were treated with each regimen for one week in vitro. RESULTS: Both treatments significantly reduced the number of viable stromal vascular fraction cells, as determined by the MTT assay. Moreover, combined TDF, 3TC, and DTG treatment increased FABP4 and leptin expression only in subcutaneous adipose tissue. No significant changes were observed in inflammatory cytokine expression, adiponectin expression and secretion, or lipolysis in either adipose depot treated with the antiretroviral combinations. CONCLUSION: These findings suggest that the tested antiretroviral combinations may reduce stromal vascular fraction cell number and that the current first-line antiretroviral combination increases FABP4 and leptin expression in subcutaneous adipose tissue, indicating the potential impact of continued antiretroviral use on systemic metabolism in people living with HIV.