ABSTRACT
There have been no paediatric randomised trials describing the effect of planned treatment interruptions (PTIs) of antiretroviral therapy (ART) on adherence, or evaluating acceptability of such a strategy. In PENTA 11, HIV-infected children were randomised to CD4-guided PTIs (n = 53) or continuous therapy (CT, n = 56). Carers, and children if appropriate, completed questionnaires on adherence to ART and acceptability of PTIs. There was no difference in reported adherence on ART between CT and PTI groups; non-adherence (reporting missed doses over the last 3 days or marking <100 % adherence since the last clinical visit on a visual analogue scale) was 18 % (20/111) and 14 % (12/83) on carer questionnaires in the CT and PTI groups respectively (odds ratios, OR (95 % CI) = 1.04 (0.20, 5.41), χ(2) (1) = 0.003, p = 0.96). Carers in Europe/USA reported non-adherence more often (31/121, 26 %) than in Thailand (1/73, 1 %; OR (95 % CI) = 54.65 (3.68, 810.55), χ(2) (1) = 8.45, p = 0.004). The majority of families indicated they were happy to have further PTIs (carer: 23/36, 64 %; children: 8/13, 62 %), however many reported more clinic visits during PTI were a problem (carer: 15/36, 42 %; children: 6/12, 50 %).
Subject(s)
Anti-Retroviral Agents/administration & dosage , Antiretroviral Therapy, Highly Active/methods , HIV Infections/drug therapy , Medication Adherence , Patient Acceptance of Health Care , Adolescent , CD4 Lymphocyte Count , Caregivers/psychology , Child , Child, Preschool , Drug Administration Schedule , Europe , Female , Follow-Up Studies , HIV Infections/virology , HIV-1 , Humans , Male , Surveys and Questionnaires , Thailand , United States , Viral LoadABSTRACT
Immune activation is the best marker of HIV disease progression in both adults and children. However, the factors that drive immune activation in HIV-infected children remain incompletely understood and may differ from those in adults. Immune activation was investigated in a cohort of 93 untreated HIV-infected children, of median age 10.8 years, and 37 HIV-uninfected children. CD8(+) T cell activation, which was higher in HIV-infected than HIV-uninfected children (p<0.001), did not correlate with viral load (R=-0.03, p=0.838). Similarly, programmed death 1 (PD-1) expression on CD8(+) T cells, which was higher in HIV-infected children than HIV-uninfected children (p<0.001), was not associated with viral load (R=0.11, p=0.40), but correlated with CD8 activation (R=0.41, p=0.002). Both CD8 activation and PD-1 expression were partially driven by the magnitude of the HIV-specific CD8(+) T cell response. CD3(+)CD4(+)CD25(hi)FoxP3(+) regulatory T cells (Tregs) were depleted in HIV-infected, compared to HIV-uninfected, children [median 1.0% (IQR 0.6, 1.9) vs. 2.6% (IQR 1.7, 3.2) CD3 cells; p<0.001]. Depletion was associated with increased CD8 activation (R=-0.27, p=0.068), suggesting that the decline in Tregs may allow immune activation to increase. Taken together, immune activation and PD-1 upregulation in children are not directly driven by viral load but may be influenced by the magnitude of the immune response to HIV itself, and to the depletion of Tregs that occurs during HIV infection. Further understanding of the factors that drive immune activation in children is critical to developing future therapeutic strategies in this population.