Inflammation, cytomegalovirus and the growth hormone axis in HIV-exposed uninfected Zimbabwean infants

Objectives Despite avoiding HIV infection, HIV-exposed uninfected (HEU) infants have poorer clinical outcomes than HIV-unexposed infants, including impaired growth. The growth hormone (GH) axis is an important regulator of infant growth through hepatic synthesis of insulin-like growth-factor-1 (IGF-1), and may be disrupted by chronic inflammation and acute infections, including cytomegalovirus (CMV). We tested the hypothesis that these factors lead to disruption of the GH axis in HEU infants, which might contribute to their impaired growth. Design Sub-study of 343 infants from the ZVITAMBO trial in Harare, Zimbabwe. Methods IGF-1, growth parameters, C-reactive protein (CRP) and CMV viremia were evaluated in 243 HEU infants and 100 HIV-unexposed infants. Univariable linear and logistic regression models were used to determine associations between IGF-1 and growth parameters, CRP and CMV. Results Mean 6-week IGF-1 was significantly lower in HEU compared to HIV-unexposed infants (29.6 vs. 32.6ng/mL; P = 0.01), and associated with subsequent linear and ponderal growth through 6 months of age. CRP was inversely correlated with IGF-1 in all infants regardless of HIV exposure status (β=-0.84; P = 0.03). CMV viral loads were inversely correlated with IGF-1 in HEU (β=-1.16; P = 0.008) but not HIV-unexposed (β=0.21; P = 0.83) infants. Conclusions Overall, we found evidence for greater disruption of the GH axis in HEU compared to HIV-unexposed infants as early as 6 weeks of age, suggesting a role for reduced IGF-1 in mediating growth impairment in HEU infants. Inflammation and co-infections may be drivers of growth impairment in HEU infants by disrupting the growth hormone axis.