Do All Integrase Strand Transfer Inhibitors Have the Same Lipid Profile? Review of Randomised Controlled Trials in Naïve and Switch Scenarios in HIV-Infected Patients

Abstract

In this study, we aim to explore the effects on lipids of integrase strand transfer inhibitors (INSTIs) in naïve and switch randomised controlled trials, and compare them with protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). We reviewed phase 3/4 randomised clinical trials in the Cochrane and PubMed databases that compare an INSTI with a boosted PI, an NNRTI, or another INSTI plus one or two nucleoside/nucleotide reverse transcriptase inhibitors (NtRTIs) in naïve patients and switching strategies in HIV-infected patients. We reported the baseline plasma concentration of total cholesterol (TC), low and high-density lipoprotein cholesterol (LDL-c, HDL-c), triglycerides (TG), and the TC/HDL-c ratio, as well as the change at weeks 48 and 96, when available. In naïve HIV-infected patients, raltegravir (RAL) and dolutegravir (DTG) have a more favourable lipid profile compared with NNRTI and boosted PI. Elvitegravir (EVG/c) has a superior lipid profile compared with efavirenz and is similar to that observed with ritonavir-boosted atazanavir except in TG, which increases less with EVG/c. In naïve patients, RAL, DTG, and bictegravir (BIC) produce a similar, slight increase in lipids. In switching trials, the regimen change based on a boosted PI or efavirenz to RAL, DTG, or BIC is associated with clinically significant decreases in lipids that are minor when the change is executed on EVG/c. No changes were observed in lipids by switching trials between INSTIs. In summary, RAL, DTG, and BIC have superior lipid profiles compared with boosted-PI, efavirenz, and EVG/c, in studies conducted in naïve participants, and they are associated with a clinically significant decrease in lipoproteins by switching studies.

Efficacy, durability, and tolerability of bictegravir/emtricitabine/tenofovir alafenamide for the treatment of HIV in a real‐world setting in Belgium

“…In terms of the lipid profile, we observed a generally neutral effect on all serum lipids with no significant change from baseline. It is important to note that approximately half of the cohort were receiving an INSTI‐based regimen directly before BIC/FTC/TAF initiation, and – as previously reported – no changes are typically observed in lipids when switching between INSTIs [41]. Furthermore, since 28% of the study population were on a TDF‐based regimen directly before baseline, and given the fact that TDF has been previously reported to reduce lipid fractions [42], an increase in lipid parameters among people switching from TDF to TAF would have been expected but was not observed.…”

Higher Risk of Dyslipidemia With Coformulated Elvitegravir, Cobicistat, Emtricitabine, and Tenofovir Alafenamide than Efavirenz, Lamivudine, and Tenofovir Disoproxil Fumarate Among Antiretroviral-Naive People Living With HIV in China

“…8,9 Different ART regimens are associated with different risks for dyslipidemia. Several studies have shown that protease inhibitor-based ART was associated with increased risk for lipohypertrophy [10][11][12] ; lipoatrophy was more frequent with efavirenz than with lopinavir/r when combined with stavudine or zidovudine and less frequent when either drug was combined with tenofovir. 12,13 Integrase strand transfer inhibitors have neutral effect on lipids when compared with boosted protease inhibitor, efavirenz, and cobicistat-boosted elvitegravir (EVG/C) among antiretroviral-naive PLWH.…”

Spatial Heterogeneity of Brain Lipids in SIV-infected Macaques Treated with Antiretroviral Therapy

“…The copyright holder for this preprint this version posted September 27, 2022. ; https://doi.org/10.1101/2022.09.26.508302 doi: bioRxiv preprint after changing regimens from older protease inhibitors (86,96). Hypertension, another disorder related to lipid dysregulation, is also more prevalent in individuals receiving ART.…”

“…This occurs despite the known impact of HIV on diminishing total cholesterol levels (86,(92)(93)(94)(95). Conversely other ARTs, including raltegravir, dolutegravir, and bictegravir, have either a beneficial or minimal impact on the cholesterol profile after changing regimens from older protease inhibitors (86,96). Hypertension, another disorder related to lipid dysregulation, is also more prevalent in individuals receiving ART.…”