Improvements in subcutaneous fat, lipid profile, and parameters of mitochondrial toxicity in patients with peripheral lipoatrophy when stavudine is switched to tenofovir (LIPOTEST study)

HIV Clin Trials. 2008 Nov-Dec;9(6):407-17. doi: 10.1310/hct0906-407.

Abstract

Background: Lipoatrophy is the most stigmatizing side effect of stavudine therapy. We assessed the long-term effects of replacing stavudine with tenofovir in HIV-infected patients with lipoatrophy.

Method: Prospective switch study. Sixty-two clinically stable patients with antiretroviral therapy (ART) containing stavudine, HIV-1 RNA <50 copies/mL, and lipoatrophy at least in the face on physical examination were included. All patients switched from stavudine to tenofovir without changing any other drug. Objective (malar ultasonography, bioelectrical impedance analysis) and subjective measures of lipoatrophy were assessed.

Results: Median age at baseline was 40 years, 44 patients (71%) were male, and median time on stavudine was 4.8 years. Median malar fat thickness increased 0.8 mm (25%) 24 months after switching. Total fat mass increased 3.9 kg (21%). Plasma lactate levels decreased significantly, mainly in patients with baseline hyperlactatemia (from 3.05 to 1.19 mmol/L). Significant improvement in total cholesterol (-12%), triglycerides (-31%), and total cholesterol/HDL cholesterol ratio (-11%) was observed at Month 24.

Conclusions: In this study, switching from stavudine to tenofovir maintained durable virologic suppression when the HAART regimen included a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor, led to a slow improvement of lipoatrophy, and improved the lipid profile and lactate levels with excellent tolerability. These results support the proactive change of stavudine to tenofovir.

Publication types

  • Clinical Trial, Phase IV
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / administration & dosage
  • Adenine / analogs & derivatives*
  • Adenine / therapeutic use
  • Adult
  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / adverse effects
  • Anti-HIV Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active
  • Body Composition / drug effects
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Face
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV Protease Inhibitors / administration & dosage
  • HIV Protease Inhibitors / therapeutic use
  • HIV-1 / drug effects
  • HIV-Associated Lipodystrophy Syndrome / chemically induced
  • HIV-Associated Lipodystrophy Syndrome / drug therapy
  • HIV-Associated Lipodystrophy Syndrome / pathology*
  • Humans
  • Lactates / blood
  • Lipids / blood*
  • Male
  • Middle Aged
  • Mitochondria / drug effects
  • Organophosphonates / administration & dosage
  • Organophosphonates / therapeutic use*
  • Reverse Transcriptase Inhibitors / administration & dosage
  • Reverse Transcriptase Inhibitors / adverse effects
  • Reverse Transcriptase Inhibitors / therapeutic use*
  • Stavudine / administration & dosage
  • Stavudine / adverse effects
  • Stavudine / therapeutic use*
  • Subcutaneous Fat / diagnostic imaging
  • Subcutaneous Fat / drug effects
  • Tenofovir
  • Treatment Outcome
  • Ultrasonography

Substances

  • Anti-HIV Agents
  • HIV Protease Inhibitors
  • Lactates
  • Lipids
  • Organophosphonates
  • Reverse Transcriptase Inhibitors
  • Tenofovir
  • Stavudine
  • Adenine