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

J Acquir Immune Defic Syndr. 2021 Jun 1;87(2):794-800. doi: 10.1097/QAI.0000000000002655.

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.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alanine / therapeutic use*
  • Anti-HIV Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active / methods
  • Blood Glucose / drug effects
  • Drug Therapy, Combination
  • HIV Infections / drug therapy*
  • HIV-1 / drug effects
  • Heterocyclic Compounds, 3-Ring / therapeutic use*
  • Humans
  • Insulin Resistance / physiology
  • Lamivudine / therapeutic use*
  • Lipids / blood
  • Metabolic Syndrome / chemically induced
  • Oxazines / therapeutic use*
  • Piperazines / therapeutic use*
  • Pyridones / therapeutic use*
  • Tenofovir / analogs & derivatives*
  • Tenofovir / therapeutic use
  • Viral Load / drug effects
  • Weight Gain / drug effects

Substances

  • Anti-HIV Agents
  • Blood Glucose
  • Heterocyclic Compounds, 3-Ring
  • Lipids
  • Oxazines
  • Piperazines
  • Pyridones
  • Lamivudine
  • Tenofovir
  • dolutegravir
  • tenofovir alafenamide
  • Alanine

Associated data

  • ClinicalTrials.gov/NCT03446573