ABSTRACT.Objective. To acquire a deeper understanding of factors that influence adherence to highly active antiretroviral therapy (HAART) in a pediatric population.Methods. We performed a qualitative study of adherence in children who receive HAART in a Belgian pediatric acquired immune deficiency syndrome referral center. Eleven primary caregivers were interviewed to assess their child's adherence and influencing factors. The interview guidelines were developed on the basis of an extensive literature review. Adherence to treatment was assessed using caregivers' self-report and laboratory results. Content analysis for common items was performed, and statements of adherent and less-adherent patients were compared.Results. Three main factors influenced adherence. Adherent patients were found to internalize the medical information to a stronger extent than less-adherent patients. Adherent patients showed stronger motivation to stick to the medical regimen on the basis of personal cost-benefit analyses, ie, perceived benefits outweighed the costs or difficulties experienced. Adherent patients developed greater problem-solving capacities, ie, ways to deal with practical complications of medication intake. The interviews revealed a fourth, more dynamic component: knowledge, motivation, and capacities evolved in a progressive way, related to individual stages of coping with human immunodeficiency virus (HIV).Conclusions. The data suggest that coping with HIV and the process of establishing good adherence may be interrelated. Caregivers who accept the disease may be more likely to internalize the received information and thus develop a stronger motivation to fight for the child's life. Problem-solving skills sustain this adherence, and medication becomes a priority in the adherent caregivers' daily lives. On the contrary, less-adherent caregivers may be situated at less advanced stages of the coping process. Thus, tailor-made approaches adapted to the individual HIV-related coping strategies need to be developed to improve adherence in children and caregivers. T he introduction of antiretroviral therapy has turned human immunodeficiency virus (HIV) into a chronic, noncurable disease. Highly active antiretroviral therapy (HAART) causes viral suppression and favors immunologic reconstitution, which decreases opportunistic infections, the development of acquired immune deficiency syndrome (AIDS), and mortality. [1][2][3] Nevertheless, achieving and sustaining the required high level of adherence to a treatment regimen to control the disease remains a challenge. Dracup and Melais 4 defined adherence as "the extent to which an individual chooses behaviors that coincide with a clinical prescription achieved through negotiation between the health professional and the patient." In the case of HAART, this suggests introducing multiple, strictly timed doses of several drugs, some with a bad taste, into daily life. Moreover, adherence of Ͼ95% seems necessary to achieve viral suppression and to avoid development of viral resistance...