Excellent Adherence to Antiretrovirals in HIV+ Zambian Children Is Compromised by Disrupted Routine, HIV Nondisclosure, and Paradoxical Income Effects

INTRODUCTION: A better understanding of pediatric antiretroviral therapy (ART) adherence in sub-Saharan Africa is necessary to develop interventions to sustain high levels of adherence. METHODOLOGY/PRINCIPAL FINDINGS: Adherence among 96 HIV-infected Zambian children (median age 6, interquartile range [IQR] 2,9) initiating fixed-dose combination ART was measured prospectively (median 23 months; IQR 20,26) with caregiver report, clinic and unannounced home-based pill counts, and medication event monitoring systems (MEMS). HIV-1 RNA was determined at 48 weeks. Child and caregiver characteristics, socio-demographic status, and treatment-related factors were assessed as predictors of adherence. Median adherence was 97.4% (IQR 96.1,98.4%) by visual analog scale, 94.8% (IQR 86,100%) by caregiver-reported last missed dose, 96.9% (IQR 94.5,98.2%) by clinic pill count, 93.4% (IQR 90.2,96.7%) by unannounced home-based pill count, and 94.8% (IQR 87.8,97.7%) by MEMS. At 48 weeks, 72.6% of children had HIV-1 RNA <50 copies/ml. Agreement among adherence measures was poor; only MEMS was significantly associated with viral suppression (p = 0.013). Predictors of poor adherence included changing residence, school attendance, lack of HIV disclosure to children aged nine to 15 years, and increasing household income. CONCLUSIONS/SIGNIFICANCE: Adherence among children taking fixed-dose combination ART in sub-Saharan Africa is high and sustained over two years. However, certain groups are at risk for treatment failure, including children with disrupted routines, no knowledge of their HIV diagnosis among older children, and relatively high household income, possibly reflecting greater social support in the setting of greater poverty

Agreement between measures (as shown by the difference between methods versus mean adherence value for each child).

<p>The Bland-Altman plots in this figure show pair wise agreement between adherence methods. Each plot indicates the difference between two methods on the vertical axis against the mean of the same methods on the horizontal axis. Data points above the zero line occur when the first method shows higher adherence than the second. On the horizontal axis, data points to the right indicate high adherence from both methods, in which case the maximum possible difference between them is shown by the angled lines.</p

Predictors of the number of non-adherent days per quarter.

<p>IRR – Incidence rate ratio, all factors time updated except for sex.</p>a.<p> Overall p-value for age and sex.</p>b.<p> P-value for interaction between age and sex.</p

Follow-up, summary of adherence measures and agreement between methods.

a.<p> Percentage of follow-up visits with no missed dose reported during previous month.</p>b.<p> Agreement between the last missed dose question and other methods should be interpreted separately (e.g. 90% adherent for the last missed dose means that no treatment was missed in nine periods out of ten, but does not indicate the level of non-adherence in those periods).</p

Association between adherence measures and viral load.

<p>Association between adherence measures and viral load.</p

Characteristics at ART initiation.

a.<p> Other statistics are indicated in the second column.</p>b.<p> UK 1990 growth reference; WHO 2007 reference only available to 10 years. For children to age 10, the average UK weight Z-score was 0.5 lower than the WHO reference and the average UK height Z-score was 0.1 higher than WHO reference.</p>c.<p> Missing data for one child.</p