Evaluation of adherence measures in infants receiving daily nevirapine suspension for prevention of mother-to-child transmission of HIV.

Abstract

INTRODUCTION Adherence to antiretroviral treatment regimens in children has been substantially researched, however data pertaining to adherence to prophylactic regimens in the paediatric population, especially infants, is not readily available. As adherence to an antiretroviral treatment regimen is central to ensuring that expected benefits are achieved, adherence to a prophylactic regimen is as important in Human Immunodeficiency Virus (HIV) prevention. The HPTN 046 study was a prospective cohort study conducted from June 2008 to March 2010 in South Africa (Durban), Tanzania, Zimbabwe and Uganda. All enrolled infants received open label nevirapine suspension (10mg/ml) up to 6 weeks of age (day 42), at which point they were randomised to receive nevirapine suspension or placebo till 6 months of age. The dosing regimen for the first 6 weeks was as follows: 0.6ml (6mg) once daily from 3 to 7 days after birth to 2 weeks of age, 1.5ml (15mg) once daily from 2 to5 weeks of age and 1.8ml (18mg) once daily from 5 to 6 weeks (42 days) of age. Adherence to medication can be measured by various methods. The aim of this study was to ascertain the reliability of maternal verbal reports in measuring adherence to antiretroviral prophylaxis in infants in the first 6 weeks of life and evaluating the unused returned medication as an alternative method of measuring adherence. OBJECTIVES: 1. To measure adherence to daily use of nevirapine prophylaxis in infants at 2, 5 and 6 weeks of age by use of maternal verbal reports. 2. To measure adherence to daily use of nevirapine prophylaxis in infants at 2, 5 and 6 weeks of age by assessing the volume of unused returned nevirapine suspension. 3. To compare the sensitivity and specificity of maternal verbal reports and unused returned nevirapine suspension in relation to plasma nevirapine concentration. 4. To describe maternal and infant characteristics in association with adherence as measured by maternal verbal reports. METHODOLOGY: Main study: The HPTN 046 Study Measurement of adherence by maternal verbal reports: Enrolled participants’ mothers were administered a questionnaire regarding infant dosing and number of missed doses. This data was transferred into case report forms and captured into the main HPTN 046 database. Measurement of adherence by assessment of unused returned medication: Mothers of participants were requested by counsellors to return bottles with remaining medication from the previous visit at each subsequent appointment. At the 2 week, 5 week and 6 week visits, unused medication bottles were returned and weighed to determine adherence. The weight was converted to volume using the density formula (mass/volume). The dose taken was calculated by subtracting the returned volume from 20ml (volume of a full bottle). The number of missed doses was calculated from considering the expected volume that should have been taken and the actual volume taken. Substudy: The substudy was a retrospective cohort study of the HPTN 046 study. Measurement of adherence by plasma nevirapine level: In the substudy, plasma nevirapine concentrations were determined in a small sample of the substudy population for the purpose of comparing maternal verbal reports to weighed returned medication. Pharmacy records containing adherence data calculated from unused returned medication were captured and demographic and verbal report adherence data were extracted from the main electronic HPTN 046 database at 2, 5 and 6 weeks. All data were captured on a Microsoft Excel document and analysed using EPI-info (Version 3.4.3) and Stata (Version 12). RESULTS: The average adherence by maternal verbal reports and unused returned medication were 97.3% among 213 infants and 94.0% among 204 infants respectively. When evaluated against plasma NVP concentration >100ng/ml among 37 infants, the true adherence of maternal verbal reports and unused returned medication were 87.7% and 71.3% respectively. The sensitivity and specificity of maternal verbal reports against a plasma nevirapine concentration of ≤ 100ng/ml to detect a missed dose in the previous 3 days were 75% and 78% (p=0.03) respectively. Overall, among infants who were classified as adherent by maternal verbal reports and unused returned medication, 88.4% and 87.4% of infants attained a nevirapine concentration above 100ng/ml respectively. CONCLUSION: Maternal verbal reports are a more reliable measure of adherence to infant antiretroviral prophylaxis in the first 6 weeks of life when compared to assessment of unused medication returned.