Anthropometric measurements and lipid profiles to detect early lipodystrophy in antiretroviral therapy experienced HIV-infected children in the CHAPAS-3 trial.

BACKGROUND: Few studies have investigated objective markers of lipodystrophy in African children. We compared body circumferences, skin-fold thickness (SFT) and lipids in antiretroviral therapy (ART)-naive and stavudine (d4T)-exposed children with HIV-uninfected controls. METHODS: In the CHAPAS-3 trial, HIV-infected children (ART-naive or on d4T for ≥2 years without clinical lipodystrophy) were randomized to d4T, abacavir or zidovudine with lamivudine (3TC) plus a non-nucleoside reverse transcriptase inhibitor. Mid-upper-arm circumference (MUAC) and calf circumference (CC), SFT (biceps, triceps, sub-scapular and supra-iliac) and fasting lipids (total cholesterol [TC], low-density lipoprotein [LDL], high-density lipoprotein [HDL] and triglycerides [TRIG]) were measured at randomization in all HIV-infected children, and in HIV-uninfected controls. Age- and sex-adjusted z-scores of MUAC, CC, SFT and the sum of SFT (SSF) using Dutch reference data were compared across groups using linear regression. RESULTS: Of 496 children, 49% were male, 299 (median age 2.5 years [IQR 1.5-4.0]) were ART-naive, 109 (median age 6 years [IQR 5.5-7.0]) were ART-experienced and 88 (median age 2.2 years [IQR 1.5-3.0]) were control children. Overall, 100% and 95% of ART-experienced children had been on d4T plus 3TC and nevirapine, respectively, for a median 3.5 years (IQR 2.6-4.2). Mean (sd) weight-for-age z-scores and MUAC z-scores were -1.51 (1.29) versus -0.90 (0.88) versus -0.33 (1.15) and -1.56 (1.25) versus -1.24 (0.97) versus -0.65 (1.06) in ART-naive versus -experienced versus controls, respectively (all P<0.02). The mean (sd) of SSF was lower in the ART-experienced (-0.78 [1.28]) than in the ART-naive (-0.32 [1.09]; P<0.0001) children and controls (-0.29 [0.88]; P<0.002). ART-experienced children had higher mean fasting TC, LDL and HDL but lower TRIG compared to ART-naive children (P-values <0.0001), and higher TC and HDL but lower TRIG compared to controls (P-values <0.01). CONCLUSIONS: In ART-experienced children on d4T-containing regimens, we observed lower SFT and higher TC and LDL values compared to ART-naive children and HIV-uninfected controls.

Excellent adherence to antiretrovirals in HIV+ Zambian children is compromised by disrupted routine, HIV nondisclosure, and paradoxical income effects.

INTRODUCTION: A better understanding of pediatric antiretroviral therapy (ART) adherence in sub-Saharan Africa is necessary to develop interventions to sustain high levels of adherence. METHODOLOGY/PRINCIPAL FINDINGS: Adherence among 96 HIV-infected Zambian children (median age 6, interquartile range [IQR] 2,9) initiating fixed-dose combination ART was measured prospectively (median 23 months; IQR 20,26) with caregiver report, clinic and unannounced home-based pill counts, and medication event monitoring systems (MEMS). HIV-1 RNA was determined at 48 weeks. Child and caregiver characteristics, socio-demographic status, and treatment-related factors were assessed as predictors of adherence. Median adherence was 97.4% (IQR 96.1,98.4%) by visual analog scale, 94.8% (IQR 86,100%) by caregiver-reported last missed dose, 96.9% (IQR 94.5,98.2%) by clinic pill count, 93.4% (IQR 90.2,96.7%) by unannounced home-based pill count, and 94.8% (IQR 87.8,97.7%) by MEMS. At 48 weeks, 72.6% of children had HIV-1 RNA <50 copies/ml. Agreement among adherence measures was poor; only MEMS was significantly associated with viral suppression (p = 0.013). Predictors of poor adherence included changing residence, school attendance, lack of HIV disclosure to children aged nine to 15 years, and increasing household income. CONCLUSIONS/SIGNIFICANCE: Adherence among children taking fixed-dose combination ART in sub-Saharan Africa is high and sustained over two years. However, certain groups are at risk for treatment failure, including children with disrupted routines, no knowledge of their HIV diagnosis among older children, and relatively high household income, possibly reflecting greater social support in the setting of greater poverty.