Adherence to isoniazid prophylaxis among HIV-infected children: a randomized controlled trial comparing two dosing schedules.
BACKGROUND
Tuberculosis contributes significantly to morbidity and mortality among HIV-infected children in sub-Saharan Africa. Isoniazid prophylaxis can reduce tuberculosis incidence in this population. However, for the treatment to be effective, adherence to the medication must be optimized. We investigated adherence to isoniazid prophylaxis administered daily, compared to three times a week, and predictors of adherence amongst HIV-infected children.


METHODS
We investigated adherence to study medication in a two centre, randomized trial comparing daily to three times a week dosing of isoniazid. The study was conducted at two tertiary paediatric care centres in Cape Town, South Africa. Over a 5 year period, we followed 324 HIV-infected children aged >or= 8 weeks. Adherence information based on pill counts was available for 276 children. Percentage adherence was calculated by counting the number of pills returned. Adherence >or= 90% was considered to be optimal. Analysis was done using summary and repeated measures, comparing adherence to the two dosing schedules. Mean percentage adherence (per child during follow-up time) was used to compare the mean of each group as well as the proportion of children achieving an adherence of >or= 90% in each group. For repeated measures, percentage adherence (per child per visit) was dichotomized at 90%. A logistic regression model with generalized estimating equations, to account for within-individual correlation, was used to evaluate the impact of the dosing schedule. Adjustments were made for potential confounders and we assessed potential baseline and time-varying adherence determinants.


RESULTS
The overall adherence to isoniazid was excellent, with a mean adherence of 94.7% (95% confidence interval [CI] 93.5-95.9); similar mean adherence was achieved by the group taking daily medication (93.8%; 95% CI 92.1-95.6) and by the three times a week group (95.5%; 95% CI 93.8-97.2). Two-hundred and seventeen (78.6%) children achieved a mean adherence of >or= 90%. Adherence was similar for daily and three times a week dosing schedules in univariate (odds ratio [OR] 0.88; 95% CI 0.66-1.17; P = 0.38) and multivariate (adjusted OR 0.85; 95% CI 0.64-1.11; P = 0.23) models. Children from overcrowded homes were less adherent (adjusted OR 0.71; 95% CI 0.54-0.95; P = 0.02). Age at study visit was predictive of adherence, with better adherence achieved in children older than 4 years (adjusted OR 1.96; 95% CI 1.16-3.32; P = 0.01).


CONCLUSIONS
Adherence to isoniazid was excellent regardless of the dosing schedule used. Intermittent dosing of isoniazid prophylaxis can be considered as an alternative to daily dosing, without compromising adherence or efficacy.


BACKGROUND
Clinical Trials NCT00330304.
le Roux
Stanzi M
SM
School of Child and Adolescent Health, University of Cape Town, South Africa. stanzi.leroux@gmail.com
Cotton
Mark F
MF
Golub
Jonathan E
JE
le Roux
David M
DM
Workman
Lesley
L
Zar
Heather J
HJ
D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D005260:Female; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007538:Isoniazid / Q000008:administration & dosage* / Q000627:therapeutic use*; D008297:Male; D013019:South Africa; D014376:Tuberculosis / Q000188:drug therapy*; D016903:Drug Monitoring
D000995:Antitubercular Agents; D007538:Isoniazid