The Pediatric infectious disease journal · 2015
Prevalence of lipodystrophy and metabolic abnormalities in HIV-infected African children after 3 years on first-line antiretroviral therapy.
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Bwakura-Dangarembizi Mutsawashe, Musiime Victor, Szubert Alexander J, Prendergast Andrew J, Gomo Zvenyika A, Thomason Margaret J, Musarurwa Cuthbert, Mugyenyi Peter, Nahirya Patricia, Kekitiinwa Adeodata, Gibb Diana M, Walker Ann S, Nathoo Kusum, ARROW Trial Team
Аннотация
BACKGROUND: Most pediatric lipodystrophy data come from high-income/middle-income countries, but most HIV-infected children live in sub-Saharan Africa, where lipodystrophy studies have predominantly investigated stavudine-based regimens.
METHODS: Three years after antiretroviral therapy (ART) initiation, body circumferences and skinfold thicknesses were measured (n = 590), and fasted lipid profile assayed (n = 325), in children from 2 ARROW trial centres in Uganda/Zimbabwe. Analyses compared randomization to long-term versus short-term versus no zidovudine from ART initiation [unadjusted; latter 2 groups receiving abacavir+lamivudine+non-nucleoside-reverse-transciptase-inhibitor (nNRTI) long-term], and nonrandomized (confounder-adjusted) receipt of nevirapine versus efavirenz.
RESULTS: Body circumferences and skinfold thicknesses were similar regardless of zidovudine exposure (P > 0.1), except for subscapular and supra-iliac skinfolds-for-age which were greater with long-term zidovudine (0.006 < P < 0.047). Circumferences/skinfolds were also similar with efavirenz and nevirapine (adjusted P > 0.09; 0.02 < P < 0.03 for waist/waist-hip-ratio). Total and high-density lipoprotein (HDL)-cholesterol, HDL/triglyceride-ratio (P < 0.0001) and triglycerides (P = 0.01) were lower with long-term zidovudine. Low-density lipoprotein (LDL)-cholesterol was higher with efavirenz than nevirapine (P < 0.001). Most lipids remained within normal ranges (75% cholesterol, 85% LDL and 100% triglycerides) but more on long-term zidovudine (3 NRTI) had abnormal HDL-cholesterol (88% vs. 40% short/no-zidovudine, P < 0.0001). Only 8/579(1.4%) children had clinical fat wasting (5 grade 1; 3 grade 2); 2(0.3%) had grade 1 fat accumulation.
CONCLUSIONS: Long-term zidovudine-based ART is associated with similar body circumferences and skinfold thicknesses to abacavir-based ART, with low rates of lipid abnormalities and clinical lipodystrophy, providing reassurance where national programs now recommend long-term zidovudine. Efavirenz and nevirapine were also similar; however, the higher LDL observed with efavirenz and lower HDL observed with zidovudine suggests that zidovudine+lamivudine+efavirenz should be investigated in future.
METHODS: Three years after antiretroviral therapy (ART) initiation, body circumferences and skinfold thicknesses were measured (n = 590), and fasted lipid profile assayed (n = 325), in children from 2 ARROW trial centres in Uganda/Zimbabwe. Analyses compared randomization to long-term versus short-term versus no zidovudine from ART initiation [unadjusted; latter 2 groups receiving abacavir+lamivudine+non-nucleoside-reverse-transciptase-inhibitor (nNRTI) long-term], and nonrandomized (confounder-adjusted) receipt of nevirapine versus efavirenz.
RESULTS: Body circumferences and skinfold thicknesses were similar regardless of zidovudine exposure (P > 0.1), except for subscapular and supra-iliac skinfolds-for-age which were greater with long-term zidovudine (0.006 < P < 0.047). Circumferences/skinfolds were also similar with efavirenz and nevirapine (adjusted P > 0.09; 0.02 < P < 0.03 for waist/waist-hip-ratio). Total and high-density lipoprotein (HDL)-cholesterol, HDL/triglyceride-ratio (P < 0.0001) and triglycerides (P = 0.01) were lower with long-term zidovudine. Low-density lipoprotein (LDL)-cholesterol was higher with efavirenz than nevirapine (P < 0.001). Most lipids remained within normal ranges (75% cholesterol, 85% LDL and 100% triglycerides) but more on long-term zidovudine (3 NRTI) had abnormal HDL-cholesterol (88% vs. 40% short/no-zidovudine, P < 0.0001). Only 8/579(1.4%) children had clinical fat wasting (5 grade 1; 3 grade 2); 2(0.3%) had grade 1 fat accumulation.
CONCLUSIONS: Long-term zidovudine-based ART is associated with similar body circumferences and skinfold thicknesses to abacavir-based ART, with low rates of lipid abnormalities and clinical lipodystrophy, providing reassurance where national programs now recommend long-term zidovudine. Efavirenz and nevirapine were also similar; however, the higher LDL observed with efavirenz and lower HDL observed with zidovudine suggests that zidovudine+lamivudine+efavirenz should be investigated in future.