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Improved adipose tissue function with initiation of protease inhibitor-only ART
Robert T Maughan1, Eoin R Feeney2, Emilie Capel3
1HIV Molecular Research Group, School of Medicine, University College Dublin, Dublin, Ireland robert.maughan@ucdconnect.ie.
The Journal of Antimicrobial Chemotherapy
|August 13, 2016
Summary
Initiating protease inhibitor-only antiretroviral therapy (ART) in HIV patients did not cause subcutaneous adipose tissue (SAT) toxicity. Observed changes in SAT indicate a return to health, not lipodystrophy.
Area of Science:
- HIV/AIDS research
- Metabolic disorders
- Molecular biology
Background:
- Antiretroviral therapy (ART) containing HIV protease inhibitors (PIs) has been linked to subcutaneous adipose tissue (SAT) toxicity, potentially causing lipodystrophy and insulin resistance.
- The specific impact of PI-only ART on SAT function in ART-naive individuals remains unclear.
Purpose of the Study:
- To investigate the effects of initiating PI-only ART on SAT function in ART-naive subjects.
- To determine if PI-only ART contributes to SAT toxicity or lipodystrophy.
Main Methods:
- A 24-week study (HIVNAT-019) involving 48 ART-naive Thai adults initiating PI-only ART (lopinavir/ritonavir/saquinavir).
- Assessments included fasting metabolic parameters, body composition, and molecular analyses of SAT biopsies (transcriptional, protein, mtDNA, histology) at baseline, week 2, and week 24.
- ClinicalTrials.gov registration: NCT00400738.
Main Results:
- Over 24 weeks, limb fat increased, and adipocyte size increased (decreased adipocyte density).
- Mitochondrial function appeared improved, indicated by increased mtDNA and specific protein expression changes.
- Despite molecular markers suggesting potential insulin resistance, overall clinical insulin sensitivity (HOMA-IR) remained unchanged.
Conclusions:
- Initiation of PI-only ART demonstrated minimal evidence of SAT toxicity in ART-naive patients.
- Observed SAT changes were consistent with a recovery or return to health, rather than lipodystrophy development.
