Reported Adherence as a Determinant of Response to Highly Active Antiretroviral Therapy in Children Who Have Human Immunodeficiency Virus Infection

Objective. The complexity of highly ac- tive antiretroviral therapy (HAART), with multiple med- ications, formulations, and dosing intervals, makes ad- herence challenging. Little is known about the adherence of children to HAART. The objective of this study was to identify correlates of adherence to HAART and the rela- tionship between adherence and study outcomes in a pediatric clinical trial. Methods. Pediatric AIDS Clinical Trials Group 377 is a phase I/II randomized trial of 4 HAART regimens in antiretroviral-experienced, clinically stable children aged 4 months to 17 years. The 4 treatment arms include var- ious 3- or 4-drug combinations of d4T, 3TC, nevirapine, ritonavir, and nelfinavir. After informed consent was obtained, 193 children were enrolled between December 1997 and September 1998. Questionnaires were devel- oped to collect subject- or caregiver-reported adherence to study medications and to identify problems associated with medication administration. Every 3 months, the number of doses of each medication missed during the 3 days preceding the study visit was recorded. Full adher- ence (FA) and non-full adherence were defined as miss- ing no doses and missing at least 1 dose, respectively. Results. Adherence data from study week 48 or the most recent study visit were available for 125 children (week 48 for 109 children). Overall, 70% of children re- ported FA and 30% reported non-full adherence. Adher- ence did not differ by treatment arm, age, or the child's knowledge of his or her human immunodeficiency virus infection status. There was a suggestion that adherence was less for white than nonwhite children (40% vs 73% FA) and did not differ between black and Hispanic chil- dren. Rates of FA were 82% for d4T, 79% for 3TC, 83% for nevirapine, 84% for ritonavir, and 68% for nelfinavir. Despite the similar rates of FA, difficulties with taking specific medications were reported most frequently for ritonavir and nelfinavir. These included poor taste, pa- tient refusal, and scheduling problems. Adherence was associated with the virologic response: FA was seen in 92% of children with >2 log10 drop in viral load and in 64% with <2 log10 drop in viral load. Conclusion. In children, reported adherence predicts the virologic response to HAART therapy and is a useful measure of adherence. Interventions and regimens to increase adherence to HAART should result in an im- proved outcome. Pediatrics 2002;109(4). URL: http:// www.pediatrics.org/cgi/content/full/109/4/e61; adherence, compliance, HIV, antiretroviral therapy, protease inhibi- tors.