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

Abstract

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.

Gut microbiota alterations after switching from a protease inhibitor or efavirenz to raltegravir in a randomized, controlled study

“…Adult HIV-positive patients with ongoing EFV-based or a PI-based ART regimen and with BMI at least 25 kg/m 2 together with at least one metabolic syndrome component or with radiologically confirmed fatty liver were invited to participate in a randomized, controlled study to evaluate the effect of switching EFV or a PI to RAL on liver fat, body composition and on gut microbiota. The changes in liver fat and body composition were reported previously [10]. Briefly, 45 participants stratified by gender and ART class, were randomized 1 : 1 to switch EFV or a PI to RAL 1200 mg once daily with no other changes in the ART (RAL group), or to continue the unchanged EFV- or PI-containing regimen (EFV/PI group); patient disposition is shown in Supplementary Figure 1, http://links.lww.com/QAD/C701.…”

“…The main clinical findings of the present study [10] were somewhat controversial including weight gain but improved inflammatory parameters in RAL as compared with EFV/PI group. One may hypothesize that an increased gut microbiota diversity in RAL group could contribute to the improvement in the inflammatory markers.…”

“…Previously, we reported weight gain and increase in body fat and subcutaneous adipose tissue volume when switching from efavirenz (EFV) or a PI to RAL in PWH with good virological response [10]. Regardless of weight gain, liver fat content and visceral adipose tissue volume remained unchanged, while circulating lipids and inflammatory markers improved in patients who switched to RAL as compared with those who continued unchanged ART [10].…”

Switch to a raltegravir‐based antiretroviral regimen in people with HIV and non‐alcoholic fatty liver disease: A randomized controlled trial

“…The potential effect of a switch to raltegravir on NAFLD remains unclear. Two previous randomized controlled trials (RCTs) found improvement in HS in people with HIV switched from an efavirenz-based regimen to raltegravir, but one trial was conducted in patients co-infected with hepatitis C virus (HCV), while the other included people with HIV and having metabolic syndrome rather than NAFLD [11,12]. Therefore, this RCT aimed to investigate the effect of switching to a raltegravir-based regimen on NAFLD spectrum and metabolic parameters in people with HIV with NAFLD.…”

Annual Meeting of the Canadian Association for the Study of the Liver (CASL), the Canadian Network on Hepatitis C (CanHepC), the Canadian Association of Hepatology Nurses (CAHN), and the Canadian NASH Network 2022 Abstracts

“…Nonalcoholic fatty liver disease (NAFLD) is a major comorbidity among people living with HIV (PLWH) ( 1 ). In such population, NAFLD is associated with metabolic disorders and exposure to certain antiretroviral therapies (ART) ( 2 ). The aggressive nature of hepatic steatosis (HS) in HIV patients, mandates exploring less steatogenic antiretroviral options.…”