Switching to either raltegravir or dolutegravir from a ritonavir-boosted protease inhibitor during combination antiretroviral therapy (ART) has been associated with improved serum leptin levels and homeostasis model assessment of insulin resistance (HOMA) index scores in people with HIV infection, according to a study recently published in the Journal of Antimicrobial Chemotherapy. Insulin sensitivity showed similar improvement.
This prospective cohort analysis included 86 participants with HIV, 86% of whom were men with the mean age of 45.7 years, who had received at least 2 years of combination ART. Inclusion criteria included combination ART regimens that were unchanged during the previous year and included 1 ritonavir-boosted protease inhibitor and tenofovir disoproxil fumarate/emtricitabine; 6 months of plasma HIV RNA levels below 50 copies/mL; and a switch to either raltegravir or dolutegravir from a ritonavir-boosted protease inhibitor during the study period. Participants were nondiabetic. Primary end points included changes in insulin, glucose, and homeostasis model assessment of insulin resistance index score during a 12-month follow-up period. A Student’s t-test or Fisher’s exact test were used to evaluate between-group differences.
Of the 86 participants meeting inclusion criteria, 45 switched to raltegravir and 41 switched to dolutegravir. Both groups experienced a significant decrease in mean leptin/insulin concentration over the follow-up period: the raltegravir group demonstrated a -0.61 ng/mL (P<.001) change in leptin, a -2.5 mIU/L (P=.008) change in insulin, as well as a -0.55 (P=.004) change in mean homeostasis model assessment of insulin resistance index score; the participants of the dolutegravir group showed a -0.54 ng/mL (P=.005), -2.1 mIU/L (P=.017), and -0.49 (P<.001) changes, respectively. Lipid levels also decreased with both raltegravir and dolutegravir. These changes were statistically comparable in both groups.
Limitations to this study included a lack of random assignment of participants, which may have affected treatment choice, as well as a small sample size and a relatively short period of observation. The medical records used to collect data could also have been incomplete or inaccurate.
The study researchers concluded that “in adults receiving a [ritonavir-boosted protease inhibitor]-based [combination ART with virologic] suppression, the switch from a [protease inhibitor] to raltegravir or dolutegravir proved effective in improving insulin sensitivity, and also reduced certain inflammatory markers and lipid parameters. Further, larger, randomized trials are clearly needed in order to better define the effect of these switch strategies on glucose metabolism in patients with HIV infection.”
Calza L, Colangeli V, Borderi M, et al. Improvement in insulin sensitivity and serum leptin concentration after the switch from a ritonavir-boosted PI to raltegravir or dolutegravir in non-diabetic HIV-infected patients [published online December 12, 2018]. J Antimicrob Chemother. doi: 10.1093/jac/dky507