Brief Report: Improvement in Metabolic Health Parameters at Week 48 After Switching From a Tenofovir Alafenamide-Based 3- or 4-Drug Regimen to the 2-Drug Regimen of Dolutegravir/Lamivudine: The TANGO Study

Abstract

Background: In TANGO, switching to dolutegravir/lamivudine was noninferior at 48 weeks to continuing 3-/4-drug tenofovir alafenamide-based regimens in virologically suppressed individuals with HIV-1. Antiretroviral agents have been associated with weight gain and metabolic complications.

Setting: One hundred thirty-four centers; 10 countries.

Methods: We assessed weight; fasting lipids, glucose, and insulin; and prevalence of insulin resistance and metabolic syndrome at baseline and week 48 in TANGO participant subgroups by boosting agent use in baseline regimens (boosted and unboosted).

Results: In each treatment group, 74% of participants used boosted regimens at baseline. In boosted and unboosted subgroups, weight and fasting glucose changes at week 48 were small and similar between treatment groups. Overall and in the boosted subgroup, greater decreases from baseline were observed with dolutegravir/lamivudine in fasting total cholesterol (P < 0.001), low-density lipoprotein cholesterol (P < 0.001), triglycerides (P < 0.001), total cholesterol/high-density lipoprotein cholesterol ratio (overall, P = 0.017; boosted, P = 0.007), and insulin (boosted, P = 0.005). Prevalence of HOMA-IR ≥2 was significantly lower at week 48 with dolutegravir/lamivudine overall [adjusted odds ratio (aOR), 0.59; 95% confidence interval (CI), 0.40 to 0.87; P = 0.008] and in the boosted subgroup [aOR, 0.56; 95% CI, 0.36 to 0.88; P = 0.012] but not in the unboosted subgroup [aOR, 0.70; 95% CI, 0.31 to 1.58; P = 0.396]. Prevalence of metabolic syndrome at week 48 was low and consistent between treatment groups overall, with differences trending to favor dolutegravir/lamivudine in the unboosted subgroup [aOR, 0.41; 95% CI, 0.15 to 1.09; P = 0.075].

Conclusion: Generally, switching from 3-/4-drug tenofovir alafenamide-based regimens to dolutegravir/lamivudine improved metabolic parameters, particularly when switching from boosted regimens. Because of smaller sample size in the unboosted subgroup, results warrant further investigation.

Trial registration: ClinicalTrials.gov NCT03446573.

Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.

Figures

FIGURE 1.

Odds of (A) insulin resistance and (B) metabolic syndrome at week 48 with dolutegravir/lamivudine or tenofovir alafenamide–based regimen by boosting status of baseline antiretroviral regimen. Includes participants with no missing baseline covariate data and week 48 metabolic data. Participants with evidence of diabetes at baseline were excluded from HOMA-IR analysis. aOdds ratios and 95% CIs were calculated using a logistic regression model. Insulin resistance was adjusted for treatment regimen (2DR vs 3/4DR), baseline boosting status (boosted vs unboosted), race (black, other vs white), sex (female vs male), baseline BMI (continuous), baseline CD4+ cell count (continuous), age (continuous), baseline hypertension (yes vs no), baseline HOMA-IR (continuous), and treatment-by-baseline boosting status interaction. Metabolic syndrome was adjusted for treatment regimen (2DR vs 3/4DR), baseline boosting status (boosted vs unboosted), sex (female vs male), baseline hypertension (yes vs no), baseline triglycerides (borderline high, high, very high vs normal), baseline HDL-C (low, high vs normal), baseline HOMA-IR (2 to <3, 3 to <4, ≥4 vs <2), and treatment-by-baseline boosting status interaction. *P = 0.012. **P = 0.008.