Growth reconstitution following antiretroviral therapy and nutritional supplementation: systematic review and meta-analysis.
OBJECTIVE
As antiretroviral therapy (ART) expands for HIV-infected children, it is important to determine its impact on growth. We quantified growth and its determinants following ART in resource-limited (RLS) and developed settings.


METHODS
Systematic review and meta-analysis.


METHODS
We searched publications reporting growth [weight-for-age (WAZ), height-for-age (HAZ), and weight-for-height (WHZ) z scores] in HIV-infected children following ART through August 2014. Inclusion criteria were as follows: younger than 18 years; ART; at least 20 patients; growth at ART; and post-ART growth. Standardized and overall weighted mean differences were calculated using random-effects models.


RESULTS
A total of 67 articles were eligible (RLS = 54; developed settings = 13). Mean age was 5.8 years, and comparable between settings (P = 0.90). Baseline growth was substantially lower in RLS vs. developed settings (WAZ -2.1 vs. -0.5; HAZ -2.2 vs. -0.9; both P < 0.01). Rate of weight but not height reconstitution during 12 and 24 months was higher in RLS (12-month WAZ change 0.84 vs. 0.17, P < 0.01). Growth deficits persisted in RLS after 2 years ART (P = 0.04). Younger cohort age was associated with greater growth reconstitution. Protease inhibitor and nonnucleoside reverse-transcriptase inhibitor regimens yielded comparable growth. Adjusting for age and setting, cohorts with nutritional supplements had greater growth gains (24-month rate difference: WAZ 0.55, P = 0.03; HAZ 0.60, P = 0.007). Supplement benefits were attenuated after adjusting for baseline cohort growth.


CONCLUSIONS
RLS children had substantial growth deficits compared with developed settings counterparts at ART; growth shortfalls in RLS persisted despite reconstitution. Earlier age and nutritional supplementation at ART may improve growth outcomes. Scant data on supplementation limit evaluation of impact and underscores need for systematic data collection regarding supplementation in pediatric ART programmes/cohorts.
aDepartment of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas bDepartment of Global Health cDepartment of Biostatistics dDivision of Vaccine and Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle, Washington eDepartment of Pediatrics, Boston Medical Center, Boston, Massachusetts fDepartment of Medicine gDepartment of Pediatrics hDepartment of Epidemiology, University of Washington, Seattle, Washington, USA.
Christine J
CJ
McGrath
Lara
L
Diener
Barbra A
BA
Richardson
Elizabeth
E
Peacock-Chambers
Grace C
GC
John-Stewart
D000293:Adolescent; D000883:Anthropology; D044966:Anti-Retroviral Agents / Q000008:administration & dosage*; D056808:Biostatistics; D002648:Child; D002657:Child Development; D002675:Child, Preschool; D019049:Developed Countries; D003906:Developing Countries; D019587:Dietary Supplements; D005260:Female; D015658:HIV Infections / Q000628:therapy*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male
D044966:Anti-Retroviral Agents