The Role of Cognitive Functioning in Medication Adherence of Children and Adolescents with HIV Infection

Advances in medical treatment, through combination antiretroviral therapy (ART) and highly active ART (HAART) with protease inhibitors (PIs), have resulted in improved health outcomes among children with human immunodeficiency virus (HIV) infection (DeMartino et al., 2000; Gortmaker et al., 2001). Adherence to HAART regimens is difficult, however, due to the demanding nature of antiretroviral treatment and other unique challenges faced by children and adolescents with HIV and their caregivers. Antiretroviral medications, particularly regimens containing PIs, share characteristics that amplify the inherent difficulties of medication adherence in children and adolescents: poor palatability, heavy pill burden, dietary restrictions, acute and long-term side effects, and restrictions on daily schedules (Reddington et al., 2000; Van Dyke et al., 2002). Children and adolescents with HIV often face other life stressors that affect their ability to achieve adherence, including parental HIV disease, poverty, and limited or inconsistent social support (Steele, Nelson, & Cole, 2007). Adherence failure is dangerous in HIV disease as it may result in diminished treatment efficacy, development of genotypically resistant mutations, viral rebound, and subsequent reduction in HIV treatment options. Despite the importance of adherence in HIV disease, our understanding of factors predictive of adherence in children and adolescents remains incomplete. Prior studies of adherence in children with HIV infection, while often atheoretical, have identified multiple contextual factors associated with adherence, including disease characteristics, features of the medication regimen, and characteristics of the caregiver and family, such as caregiver education and problem-solving skills, caregiver relationship to the child, and child and caregiver stress (Hammani et al., 2004; Martin et al., 2007; Mellins, Brackis-Cott, Dolezal, & Abrams, 2004; Naar-King et al., 2006; Pontali, 2005). Child and adolescent developmental issues, including older age, knowledge of HIV diagnosis, and adjustment to chronic illness have also been implicated, although findings remain inconsistent (Simoni et al., 2007; Williams et al., 2006). Neurocognitive impairment, due to the neuropathological effects of HIV infection, is a significant complication of perinatally acquired HIV infection (Van Rie, Harrington, Dow, & Robertson, 2007). It has been associated with nonadherence in adults with HIV (Hinkin et al., 2004) and may provoke similar risk in children and adolescents. Global or mild cognitive deficits, if present, may impede or delay development of those functional skills essential for adherence, such as understanding and following parental and provider directions, remembering schedules and dosage, and communicating needs effectively. The purpose of this study was to examine cognitive functioning in children and adolescents with HIV, and to evaluate its relationship with medication adherence. We hypothesized that adherence to ART and HAART with PIs will be compromised in the presence of neurocognitive deficits in children and adolescents with HIV infection. We also evaluated potential confounding factors, including demographic characteristics, biological markers of health, medication and adherence factors, and child and family psychosocial characteristics that have been associated with medication adherence in previous investigations.