Date Published: March 21, 2019
Publisher: Public Library of Science
Author(s): Sarah Rylance, Jamie Rylance, Grace McHugh, Edith Majonga, Tsitsi Bandason, Hilda Mujuru, Kusum Nathoo, Sarah Rowland-Jones, Marc Y. R. Henrion, Victoria Simms, Rashida A. Ferrand, Jakob Usemann.
Chronic respiratory disease is a common cause of morbidity in children with HIV infection. We investigated longitudinal lung function trends among HIV-infected children, to describe the evolution of lung disease and assess the effect of anti-retroviral therapy (ART).
Prospective follow-up of two cohorts of HIV-infected children, aged 6 to 16 years, in Harare, Zimbabwe; one group were ART-naïve at enrolment, the other established on ART for a median of 4.7-years. Standardised spirometric assessments were repeated over a 2-year follow-up period. Forced expiratory volume (FEV1) and forced vital capacity (FVC) were expressed as Global Lung Initiative defined z-scores (FEV1z and FVCz). Linear mixed-effects regression modelling of lung function was performed, with co-variate parameters evaluated by likelihood ratio comparison.
We included 271 ART-naïve and 197 ART-established children (median age 11 years in both groups) incorporating 1144 spirometric assessments. Changes in FEV1 and FVC were associated with age at ART initiation and body mass index for both cohorts. Our models estimate that ART initiation earlier in life could prevent a deterioration of 0.04 FVCz/year. In the ART-naïve cohort, likelihood ratio comparison suggested an improvement in 0.09 FVCz/year during the two years following treatment initiation, but no evidence for this among participants established on ART.
Early ART initiation and improved nutrition are positively associated with lung function and are important modifiable factors. An initial improvement in lung growth was seen in the first 2-years following ART initiation, although this did not appear to be sustained beyond this timeframe.
Increasing numbers of children with HIV, who would previously have died in early infancy, are now reaching adolescence due to the remarkable global scale-up of paediatric antiretroviral therapy (ART). In addition, one-third of HIV-infected infants in Sub-Saharan Africa, where 90% of the world’s HIV-infected children live, have slow-progressing disease with a median survival of more than a decade, even without ART.[2, 3]
Detailed methods have been previously published for both cohorts.[5, 6] Children were eligible if aged 6–16 years, were not acutely unwell (no acute symptoms and not requiring hospitalisation), and were not receiving TB treatment.
Data for 202 ART-experienced and 385 ART-naïve children were available; detailed baseline cohort characteristics have been published.[5, 6] Of the latter, 307 met criteria for, and were established on, ART during the follow-up period: 78 children did not receive ART during the study period, and were not included in the longitudinal data analysis, which was designed to assess the effect of ART on lung function. Table 1 summarises the baseline characteristics of both cohorts. Age and sex distributions were similar between groups (Table 1). As expected, ART-naïve participants were older at HIV diagnosis than those on treatment (median 11.0 years [IQR 9.0–13.0] vs. 4.9 years [IQR 2.8–7.5] respectively, p<0.001) and had significantly lower CD4 counts at enrolment (median 313 cells/μl [IQR 193–490] vs. 727 cells/μl [IQR 478–938], p<0.001). To our knowledge, this is the first published description of longitudinal lung function trends in HIV-infected children from Sub-Saharan Africa. Our data show that age at ART initiation and BMI both significantly explain variation in lung function (FEV1 and FVC). FVC improves over time in the 2-years following ART initiation, but this effect cannot be extrapolated beyond the period of the study. In summary, our study supports the WHO policy of immediate ART initiation in children. The beneficial effect of early ART on lung function was a consistent finding across both cohorts, and highlights a time-limited opportunity to intervene to promote optimum lung growth and development. Our data suggest that nutritional interventions may further contribute to improved lung health, although addressing both immunologic recovery and nutrition will be required to maximise benefits. Source: http://doi.org/10.1371/journal.pone.0213556