Benefit of Early ART Initiation in HIV-Infected Children and Adolescents

Early initiation of antiretroviral therapy (ART) and improved nutrition in children with HIV were positively associated with lung function and represent important modifiable factors, according to study results published in PLoS One.

A prospective follow-up of 2 cohorts in Harare, Zimbabwe, of children with HIV aged 6 to 16 years was used to investigate longitudinal lung function trends, to describe the evolution of lung disease, and to assess the effect of ART. The cohorts consisted of 271 ART-naive children and 197 children receiving ART, and incorporated 1144 spirometric assessments. Forced expiratory volume and forced vital capacity (FVC) were expressed as Global Lung Initiative-defined z-scores (FEVz and FVCz), and linear mixed effects regression modeling of lung function was performed.

The results estimated that ART initiation earlier in life could prevent a deterioration of 0.04 FVCz/year, whereas in the ART-naive cohort, a likelihood ratio comparison suggested an improvement in 0.09 FVCz/year in the 2 years after treatment initiation. There was, however, no evidence for this in participants receiving established ART regimens.

The study investigators highlighted that it was necessary to combine the data from the 2 cohorts to maximize the amount of longitudinal lung function data; this meant that measurements were collected on different follow-up schedules. For this reason, the analysis was restricted to exploring lung function and anthropometry, rather than imputing missing variables for a substantial number of participants. Further, the model was not corrected for multiple statistical testing. Researchers also reported that bias was potentially introduced if participants did not attend visits because of perceived good health or severe disease. In addition, noise within the spirometry data limited the predictive capacity of the models, and within-subject variations arose from measurement error and physiological day-to-day function. Researchers cautioned that although the latter may not be clinically significant at the individual level, it may be so at the population level.

The study investigators concluded that the beneficial effects of early ART initiation were seen across both cohorts, and the study “supports the [World Health Organization] policy of immediate ART initiation in children.” The data also highlighted that there is a time-sensitive opportunity for interventions promoting optimum lung growth and development. The study investigators also noted that their data suggested that nutritional interventions may also contribute to improved lung health, but that addressing both immunologic recovery and nutrition will be required to maximize benefits. Researchers stated that future work should investigate clinical modifiers on longitudinal lung function such as CD4 count, viral load, and previous significant respiratory infections including tuberculosis.

Reference

Rylance S, Rylance J, McHugh G, et al. Effect of antiretroviral therapy on longitudinal lung function trends in older children and adolescents with HIV-infection. PLoS One. 2019;14:e0213556.