Metabolic abnormalities and body composition of HIV-infected children on Lopinavir or Nevirapine-based antiretroviral therapy

Abstract

Background: Few studies have assessed metabolic and body composition alterations in perinatally HIV-infected African children on antiretroviral therapy (ART). We compared metabolic profiles and regional fat of children on ritonavir-boosted lopinavir (lopinavir/ritonavir), lamivudine and stavudine to those switched to nevirapine, lamivudine and stavudine.

Methods: This study evaluated metabolic and body composition outcomes in 156 HIV-infected children completing a randomised trial that assessed the continued use of lopinavir/ritonavir-based ART or switch to nevirapine-based ART in Johannesburg, South Africa (2005-2010). Fasting total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides total and regional body fat (BF) were measured. A clinical assessment for lipodystrophy (LD) was conducted.

Results: 156 children (mean age 5.1±0.8 years, mean duration of treatment 4.2±0.7 years, mean time since randomisation 3.4±0.7 years) were enrolled. 85 were randomised to the lopinavir/ritonavir group and 71 to the nevirapine group. The lopinavir/ritonavir group had lower mean HDL (1.3±0.4 vs 1.5±0.4 mmol/l, p<0.001) and higher mean TC (4.4±1.0 vs 4.1±0.8 mmol/l, p=0.097), LDL (2.6±0.9 vs 2.3±0.7 mmol/l, p=0.018) and triglycerides (1.1±0.4 vs 0.8±0.3 mmol/l, p<0.001). The lopinavir/ritonavir group had more total BF by mean skinfold sum (43±11.1 vs 39±10.1 mm, p=0.031) and BF% by bioelectrical impedance analysis (17.0±7.0 vs 14.1±8.0%, p=0.022). Thirteen (8.4%) met criteria for LD.

Conclusions: Unfavourable alterations in lipid profile and triglycerides, and differences in fat are detectable in young HIV-infected South African children receiving lopinavir/ritonavir-based regimens versus those switched to nevirapine-based regimens. Interventions to mitigate these alterations are warranted to reduce long-term cardiovascular disease risk.

Figure 1

Flow diagram of study participants in NEVEREST 2 (2005–2010) in Johannesburg, South Africa detailing the number of subjects excluded from the analysis, the reason for their exclusion, and distribution of included subjects by randomization group. Time intervals are provided in mean ± standard deviation.

Figure 2

Regional fat (as % of total) by skinfolds of children with lipodystrophy (LD+), possible LD, or no LD (LD−), as determined by clinician assessment. Children were classified as LD+, possible LD, and LD− if >2, 1, or 0 of features of lipoatrophy (i.e. sunken cheeks, temporal wasting, skinny limbs, wasting of buttocks) or lipohypertrophy (i.e increased abdominal girth, dorsal cervical enlargement, or breast enlargement) were present.