Background: Carotid intimal medial thickness (IMT) and pulse wave velocity (PWV), as measures of cardiovascular structure/function, are impaired in HIV-infected children in high-income countries. Few longitudinal data are available: none come from Africa where 90% HIV-infected children live.
Methods: ART-naïve and ART-experienced (on d4T+3TC+NNRTI for >2years, virologically suppressed at enrolment) HIV-infected children had IMT and PWV measured at baseline, 48 and 96 weeks within the CHAPAS-3 trial which evaluated d4T vs ZDV vs ABC-based first-line ART in Uganda/Zambia. Age-matched HIV-uninfected controls had a single assessment. Baseline differences between ART-naïve/experienced children vs controls, and longitudinal changes in HIV-infected children were compared using two-sample and paired t-tests respectively.
Results: In 208 ART-naïve children with median age 2.9y (IQR 1.7–4.4), median CD4% 18% (11-23) and 209 HIV-uninfected controls median age 3.0y (2.1–4.1), mean(sd) cIMT was 0.46(0.04) v 0.44(0.04)mm respectively (p=0.0001); PWV was 5.85(0.8) vs 5.67(0.74)m/sec respectively (p=0.04). Among 74 ART-experienced children on ART for mean 3.7y with median age 6.9y (5.9–8.50, median CD4% 33% (27-39) and 75 uninfected controls with median age 6.7y (5.6-8.6), mean(sd) cIMT was 0.46(0.05) vs 0.45(0.04)mm respectively (p=0.09); PWV was 5.63(0.61) vs 5.69(0.69)m/s respectively (p=0.57). In ART naïve children IMT and PWV significantly decreased from baseline (ART initiation) to week 96 mean(sd) cIMT -0.02(0.04)mm (p=0.0001), PWV -0.38(0.83)m/s (p<0.0001). In contrast whereas cIMT had significantly reduced by mean -0.2(0.06)mm (p=0.01) at week 96 in the ART experienced group PWV increased by 0.35(0.63)m/s (p<0.0001). There was no evidence that the changes differed by randomisation ART in either group (p=0.6).
Conclusions: In this large study of arterial structural and function in HIV-infected children in Africa, ART-naïve HIV-infected children had significantly poorer IMT and PWV compared to age-matched controls but significant improvement seen after 96 weeks of ART. After a mean 3.7 years on ART, HIV-infected children had cIMT and PWV comparable to uninfected age-matched controls. IMT continued to improve after a further 96 weeks on ART. ART can reverse some of the structural/functional changes caused by HIV, strengthening the argument for early diagnosis and treatment of HIV-infected infants and children.
Graph to show changes in IMT and PWV over 96 weeks in ART naive and ART experienced children with baseline data from age-matached HIV uninfected controls.