Growth differences by school-age and adolescence according to in utero and peripartum antiretroviral therapy exposure among Ugandan children

Abstract

In utero/peripartum antiretroviral (IPA) drug exposure in human immunodeficiency virus (HIV)-exposed children has established benefit for prevention of HIV mother-to-child-transmission but its association with height-for-age by adolescence is unknown. Hence we quantify IPA-associated growth differences at 6 to 18 years old among children with perinatally acquired HIV (CPHIV) infection and children HIV exposed but uninfected (CHEU) relative to children HIV unexposed and uninfected (CHUU). Cohort study. Kampala, Uganda. Two hundred thirty eight community controls and 490 children of women living with HIV born between 2000 and 2011 in a community were enrolled at 6 to 18 years of age and followed every 6 months for 1 year. Height-for-age determined at enrollment, 6 and 12 months after enrollment using the World Health Organization reference. IPA exposure was retrospectively determined from medical records and categorized as: no IPA, single-dose nevirapine with/without zidovudine (sdNVP ± AZT), sdNVP + AZT + lamivudine, or combination antiretroviral therapy (cART). Mean differences (β) with 95% confidence intervals (CIs) in height-for-age over 12 months were evaluated according to IPA exposure for CPHIV and CHEU and relative to CHUU using longitudinal linear mixed effects models adjusted for caregiver factors (sex, age, education, functioning in caregiving role, and lifetime adversity) in Statistical Analysis Software (v.9.4). Regardless of IPA type, CPHIV grew worse than CHUU by school-age/adolescence (β = -0.30, 95% CI: -0.48, -0.11). Relative to CHUU height-for-age was similar for CHEU exposed to sdNVP ± AZT (β = -0.16, 95% CI: -0.46, 0.14) and for CHEU exposed to sdNVP + AZT + lamivudine (β = 0.08, 95% CI: -0.20, 0.35). However, CHEU without any IPA exposure had lower height-for-age (β = -0.27, 95% CI: -0.52, -0.00) whereas CHEU with cART exposure had greater height-for-age (β = 0.41, 95% CI: 0.10, 0.71) in comparison with CHUU by 6 to 18 years old. Our findings suggest that CHEU may achieve height-for-age parity with CHUU by school-age and adolescent years- especially if provided benefit of effective cART in the peripartum period. However, CPHIV regardless of IPA exposure type and CHEU without IPA exposure remain at a disadvantage and will benefit from intervention to support their growth.

Figure 1.

Study base for early ART and growth association. ART = antiretroviral therapy, CPHIV = children with perinatally acquired HIV infection, CHEU = children HIV exposed uninfected, CHUU = children HIV unexposed uninfected.

Figure 2.

Early ART-associated differences in height-for-age among children born to HIV+ pregnant women from Uganda relative to children HIV unexposed uninfected at 6 to 18 years old. ART = antiretroviral therapy.