Differences in virologic and immunologic response to antiretroviral therapy among HIV-1-infected infants and children

Abstract

Background Virologic and immunologic responses to antiretroviral treatment (ART) in infants may differ from older children due to immunologic, clinical or epidemiologic characteristics. Methods Longitudinal ART responses were modeled and compared in HIV-infected infants and children enrolled in cohorts in Nairobi, Kenya. Participants were enrolled soon after HIV diagnosis, started on ART, and followed for two years. Viral load decline was compared between infant and child cohorts using a nonlinear mixed effects model and CD4% reconstitution using a linear mixed effects model. Results Among 121 infants, median age at ART was 3.9 months; among 124 children, median age was 4.8 years. At baseline, viral load (VL) was higher among infant than children (6.47 vs. 5.91 log10 copies/ml, p<0.001). Infants were less likely than children to suppress viral load to <250 copies/ml following 6 months of ART (32% infants vs. 73% children p<0.0001). CD4% was higher at baseline in infants than children (19% vs. 7.3%, p<0.001). Older children had more rapid CD4% reconstitution than infants, but failed to catch up to infant CD4%, Conclusion Despite substantially higher CD4% at ART initiation, viral suppression was significantly slower among infants than older children. New strategies are needed to optimize infant outcomes on ART.

HIV viral suppression and longevity among a cohort of children initiating antiretroviral therapy in Eastern Cape, South Africa

“…Although we did not find that age was a significant predictor of VS in multivariable models adjusted for clinical characteristics at ART initiation including VL, previous studies have found associations between younger age and lower incidence of suppression . Children with advanced disease at ART initiation take longer and are less likely to achieve VS; they are also at risk for having inadequate immune response to treatment .…”

“…Among infants starting ART at a median age of 5.9 months in pooled data from Southern Africa, only 28% and 56% achieved VS <400 copies/mL at six and twelve months . In our cohort, younger children had significantly higher VL at ART initiation compared to older children (61% of children <12 months had VL >1 million copies compared to 10% of six to twelve year olds) which has also been observed in other studies . In addition to higher VL, younger children may face greater adherence challenges as a result of medication syrups which can be difficult to administer and are highly unpalatable .…”

“…In multivariable models, age was the only factor significantly associated with VL rebound after VS <50 copies/mL; children <12 months had an almost twofold increased risk of VL rebound compared to children six to twelve years of age. A study of children starting ART in Kenya also found that infants (median age 3.9 months) had twice the incidence of VL rebound >1000 copies/mL after VS <250 copies/mL compared to older children . Sustained VL suppression is critical to achieving optimal treatment outcomes and greater efforts are needed to ensure that all children initiating treatment maintain VS.…”

“…In addition to late enrolment, differences have also been observed in rates of VS by age at ART initiation. Several studies have shown that time to VS is often prolonged in infants and younger children and that infants are less likely to fully suppress . High pretreatment viral loads (VL) and suboptimal antiretroviral formulations and regimens for this age group likely contribute to poor outcomes .…”

Viral suppression among children and their caregivers living with HIV in western Kenya

“…A range of factors can influence adherence and viral suppression for children including the child's age, familial and socio-economic environment, stigma, disclosure, and the physical and mental health status of children and caregivers [3,10,54,55]. Consistent with prior studies, we found that older child age was protective against viral non-suppression compared to child age ≤2 years [56][57][58]. This could reflect behavioural changes during childhood such as younger children refusing to take medications or the positive effects of HIV disclosure to older children, the effect of ART dosing frequency (i.e.…”