Growth and Metabolic Changes after Antiretroviral Initiation in South African Children

Background: Poor growth and metabolic disturbances remain concerns for children living with HIV (CLHIV). We describe the impact of viral load (VL) on growth and lipid outcomes in South African CLHIV <12 years initiating World Health Organization recommended first-line antiretroviral therapy (ART) from 2012 to 2015. Methods: Z scores for length-for-age (LAZ), weight-for-age (WAZ) and body mass index-for-age were calculated. Lipids (total cholesterol, low-density lipoprotein and high-density lipoprotein) were measured. Hemoglobin A1C ≥5.8 was defined as at risk for type 2 diabetes. Mixed effects models were used to assess the association of VL at ART initiation with Z scores and lipids over time. Results: Of 241 CLHIV, 151 (63%) were <3 years initiating LPV/r-based ART and 90 (37%) were ≥3 years initiating EFV-based ART. Among CLHIV <3 years, higher VL at ART initiation was associated with lower mean LAZ (ß: -0.30, P=0.03), WAZ (ß: -0.32, P=0.01) and low-density lipoprotein (ß: -6.45, P=0.03) over time. Among CLHIV ≥3, a log 10 increase in pretreatment VL was associated with lower mean LAZ (ß: -0.29, P=0.07) trending towards significance and lower WAZ (ß: -0.32, P=0.05) as well as with more rapid increases in LAZ (ß: 0.14 per year, P=0.01) and WAZ (ß: 0.19 per year, P=0.04). Thirty percent of CLHIV were at risk for type 2 diabetes at ART initiation. Conclusions: CLHIV initiating ART <3 years exhibited positive gains in growth and lipids, though high viremia at ART initiation was associated with persistently low growth and lipids, underscoring the need for early diagnosis and rapid treatment initiation. Future studies assessing the long-term cardiometabolic impact of these findings are warranted.