TY - JOUR
T1 - Liver Fat, Adipose Tissue, and Body Composition Changes after Switching from a Protease Inhibitor or Efavirenz to Raltegravir
AU - Hanttu, Anna
AU - Vuoti, Sauli
AU - Kivelä, Pia
AU - Arkkila, Perttu
AU - Lundbom, Nina
AU - Hakkarainen, Antti
AU - Lundbom, Jesper
AU - Lehtimäki, Tiina
AU - Viskari, Hanna
AU - Lehtinen, Ville
AU - Pietiläinen, Kirsi H.
AU - Sutinen, Jussi
N1 - Funding Information:
A.H. is currently employed by Orion Pharma, but the work reported in this article was completed before start of em- ployment. A.H. has received a lecture fee from Merck and conference support from Merck and Gilead. S.V. is currently employed by Janssen-Cilag, but the work reported in this article was completed before start of employment. P.K.: honoraria, lecture fees, and conference support from Gilead, Merck, and GSK/ViiV. Research grant from Gilead. P.A.: lecture fees from Merck. H.V.: conference support from Merck and Gilead. J.S.: honoraria, lecture fees, and conference support from Gilead, Merck, and GSK/ViiV. Research grant from Gilead and Merck. All other authors have no conflicts of interest to declare.
Funding Information:
This investigator-initiated study was financially supported by Merck Sharp and Dohme Corp., the manufacturer of RAL. The sponsor had no role in the study design, no access to study data, and did not participate in data analysis or writing of the article.
Publisher Copyright:
© 2021, Mary Ann Liebert, Inc., publishers.
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - adipocyte
KW - adipose tissue
KW - nonalcoholic fatty liver disease
KW - raltegravir
KW - weight gain
U2 - 10.1089/apc.2021.0106
DO - 10.1089/apc.2021.0106
M3 - Article
AN - SCOPUS:85115311551
SN - 1087-2914
VL - 35
SP - 335
EP - 341
JO - AIDS Patient Care and STDs
JF - AIDS Patient Care and STDs
IS - 9
ER -
