Metabolic effects of initiating lopinavir/ritonavir-based regimens among young children

Area of Science:

• Pediatric Infectious Diseases
• HIV/AIDS Treatment
• Metabolic Health in Children

Background:

• Resource-limited settings face challenges in selecting first-line antiretroviral therapy for young children with HIV.
• Lopinavir/ritonavir (LPV/r) based regimens are often used due to their virologic efficacy in this population.
• Long-term metabolic effects of LPV/r in children under 3 years require thorough investigation.

Purpose of the Study:

• To estimate the long-term metabolic effects of initiating lopinavir/ritonavir (LPV/r)-based regimens as first-line therapy for HIV-infected children under 3 years old.
• To compare lipid profiles and other metabolic markers between LPV/r and nevirapine (NVP)-based regimens over 7 years.
• To inform clinical practice regarding the cardiometabolic safety of LPV/r in pediatric HIV treatment.

Main Methods:

• A prospective cohort study followed 222 children on LPV/r and 227 on NVP-based regimens for 7 years post-randomization.
• Longitudinal measurements of total cholesterol and triglycerides were analyzed.
• Adipokines, inflammation markers, microbial translocation, and immune activation biomarkers were assessed at a median of 45 weeks.

Main Results:

• Children on LPV/r regimens showed significantly higher mean total cholesterol and increased risk of borderline/high cholesterol from year 3 to 7 compared to the NVP arm.
• No significant differences were observed in triglyceride levels, markers of metabolic syndrome, inflammation, microbial translocation, or immune activation between the groups.
• The increased risk for high total cholesterol (≥170 mg/dl) in the LPV/r arm was substantial, reaching over a four-fold increase by year 7.

Conclusions:

• Initiating LPV/r-based regimens in young HIV-infected children is associated with elevated total cholesterol over the long term.
• Continuous monitoring of total cholesterol is crucial for assessing and managing cardiometabolic health in children on LPV/r.
• While LPV/r demonstrates virologic superiority, its lipid-altering effects necessitate careful clinical consideration, especially with ongoing use in resource-limited settings.