Differences in body circumferences, skin‐fold thicknesses and lipid profiles among HIV‐infected African children on and not on stavudine
Authors: Musiime V , Cook A , Kayiwa J , Zangata D , Nansubuga C , Arach B , Kenny J , Wavamunno P , Kabamba D , Asiimwe A , Abongomera G , Mulenga V , Kekitiinwa A , Kityo C , Gibb D 
Published: November 2012

Purpose of the study

To compare body circumferences, skin‐fold thickness (SFT) and lipid levels (LL), as measures of lipodystrophy, among antiretroviral therapy (ART)‐naïve and experienced children at enrolment into the CHAPAS‐3 trial.

Methods

HIV‐infected children in Uganda and Zambia, either ART‐naïve or on stavudine (d4T) for ≥2 years without clinical lipodystrophy, were randomised to receive d4T, abacavir (ABC) or zidovudine (ZDV) with lamivudine and efavirenz (EFV) or nevirapine. At enrolment, mid‐upper arm (MUAC) and calf (CC) circumferences, SFT (biceps, triceps, sub‐scapular, supra‐iliac) and fasting lipids (total cholesterol (TC), low density lipo‐protein (LDL), high density lipoprotein (HDL), triglycerides (TRIG)) were measured. Age/sex adjusted z‐scores of MUAC, CC, SFT and the sum of SFT (SSF) used Dutch reference data. ART‐naïve and ART‐experienced children were compared with t‐tests using Stata v11.0.

Summary of results

Among 444 children, 224 (51%) were male and 331 (74.5%) ART‐naïve. Mean (sd) CD4% was 19.7% (10.2) versus (vs) 34.2% (7.7) in ART‐naïve vs ART‐experienced children. The ART‐naïve were younger than the ART‐experienced children (median [IQR] age 2.5 [1.5, 4.0] vs 6.0 [5.5, 7.0] years, p<0.0001). Among the ART‐experienced, 4/108 (3.7%) were on EFV and median (IQR) d4T use was 3.5 (2.7, 4.2) years. As expected, MUAC, CC, weight‐for‐age (WAZ) and height‐for‐age (HAZ) z‐scores were lower in the ART‐naïve; the ART‐experienced had lower SFT z‐scores and higher TC and HDL, but lower TRIG (Table 1).

Mean (sd)
Difference

Z‐score/ LL
ART‐naïve
ART‐experienced
Mean (95% CI)
p‐value

MUAC
−1.6 (1.3)
−1.2 (1.0)
0.3 (0.1, 0.6)
0.018

CC
−2.3 (1.5)
−1.8 (1.0)
0.5 (0.2, 0.8)
0.0006

Biceps SFT
−0.2 (0.9)
−0.4 (0.9)
−0.3 (−0.5, −0.1)
0.009

Triceps SFT
−0.4 (1.0)
−1.0 (0.8)
−0.6 (−0.8, −0.4)
<0.0001

Sub‐scapular SFT
0.1 (1.2)
0.2 (1.2)
0.1 (0.2, 0.3)
0.751

Supra‐iliac SFT
−0.3 (1.1)
−0.9 (0.9)
−0.7 (−0.9, −0.4)
<0.0001

SSF
−3.8 (0.4)
−3.9 (0.4)
−0.1 (−0.2, −0.1)
0.035

WAZ (WHO 2007 reference)
−1.5 (1.3)
−0.9 (0.9)
0.6 (0.3, 0.9)
<0.0001

HAZ (WHO 2007 reference)
−2.5 (1.6)
−1.5 (1.2)
1.0 (0.6, 1.3)
<0.0001

TC (mg/dl)
126.1 (33.8)
154.4 (27.6)
21.7 (12.5, 31.0) (age/sex adjusted)
<0.0001

LDL (mg/dl)
71.3 (29.4)
83.1 (21.2)
7.2 (−1.2, 15.5) (age/sex adjusted)
0.093

HDL (mg/dl)
26.9 (11.6)
54.1 (16.1)
23.2 (19.4, 27.1) (age/sex adjusted)
<0.0001

TRIG (mg/dl)
94.4 (70.3)
45.1 (38.6)
−30.8 (−49.6, −12.0) (age/sex adjusted)
0.001

Conclusions

Failure‐to‐thrive likely contributed to lower circumference values in ART‐naïve children. Among the ART‐experienced, thinner SFT and higher TC values could be ART (particularly d4T)‐related. Normal values, currently unavailable for African children, are being collected. During trial follow‐up, we will evaluate the effect of ABC, ZDV and d4T on development of lipodystrophy in naïve children and its reversibility in d4T‐treated children randomised to switch to ZDV/ABC.