Liver Fat, Adipose Tissue, and Body Composition Changes After Switching from a Protease Inhibitor or Efavirenz to Raltegravir

Integrase inhibitors appear to increase body weight, but paradoxically some data indicate that raltegravir (RAL) may decrease liver fat. Our objective was to study the effects of switching from a protease inhibitor (PI) or efavirenz (EFV) to RAL on liver fat, body composition, and metabolic parameters among people living with HIV (PLWH) with high risk for nonalcoholic fatty liver disease (NAFLD). We randomized overweight PLWH with signs of metabolic syndrome to switch a PI or EFV to RAL (n = 19) or to continue unchanged antiretroviral therapy (control, n = 24) for 24 weeks. Liver fat was measured by magnetic resonance spectroscopy (MRS), body composition by magnetic resonance imaging, and bioimpedance analysis; subcutaneous fat biopsies were obtained. Median (interquartile range) liver fat content was normal in RAL 2.3% (1.1–6.0) and control 3.1% (1.6–7.3) group at baseline. Liver fat and visceral adipose tissue remained unchanged during the study. Body weight [from 85.9 kg (76.1–97.7) to 89.3 (78.7–98.7), p = 0.019], body fat mass [from 20.3 kg (14.6–29.7) to 22.7 (17.0–29.7), p = 0.015], and subcutaneous adipose tissue (SAT) volume [from 3979 mL (2068–6468) to 4043 (2206–6433), p = 0.048] increased, yet, adipocyte size [from 564 pL (437–733) to 478 (423–587), p = 0.019] decreased in RAL but remained unchanged in control group. Circulating lipids and inflammatory markers improved in RAL compared to control group. The median liver fat measured by MRS was unexpectedly within normal range in this relatively small study population with presumably high risk for NAFLD contradicting high prevalence of NAFLD reported with other methods. Despite weight gain, increase in SAT together with decreased adipocyte size and reduced inflammation may reflect improved adipose tissue function. Clinical Trial Registration number: NCT03374358.