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Antiretroviral Therapy for HIV Infection in Infants and Children: Towards Universal Access: Recommendations for a Public Health Approach: 2010 Revision. Geneva: World Health Organization; 2010.

Cover of Antiretroviral Therapy for HIV Infection in Infants and Children: Towards Universal Access

Antiretroviral Therapy for HIV Infection in Infants and Children: Towards Universal Access: Recommendations for a Public Health Approach: 2010 Revision.

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16ADHERENCE TO ART

16.1. Recommendations

  1. Pill boxes/calendars/diaries or other practical tools should be used to support adherence.

The panel was not able to make strong recommendations for specific interventions due to lack of evidence. However, the principles should always be applied.

16.2. Principles

  • Adherence preparation should begin as soon as possible and before initiation of ART, but should not put the child at risk of disease progression or death through delaying the initiation of ART.
  • Adherence should be assessed at each visit, and parental, caregiver and child issues addressed to support adherence.
  • Intervene early if problems with adherence are identified, and before switching therapy.
  • Local programmes should select the most efficacious regimens and preparations, which are easiest for caregivers to administer to young children and adolescents. Child-friendly formulations are needed to facilitate adherence.

16.3. Background knowledge and evidence

Adherence is directly related to the clinical and virological outcomes of ART in infants and children [206-208]. Studies of drug adherence in adult patients in western countries have suggested that higher levels of drug adherence are associated with improved virological and clinical responses, and that rates exceeding 95% are desirable in order to maximize the benefits of ART. In low- and middle-income countries, research suggests that adherence to ART can be associated with family structure, socioeconomic status, disclosure and medication regimen [208]. It is critical to ensure optimal adherence in order to maximize the durability of first-line ART and minimize the emergence of drug resistance. Experience has demonstrated that it can be particularly difficult to adhere to daily medication regimens, especially over long periods [209]. A range of approaches to support and improve adherence have been investigated and have begun to be explored. As ART becomes increasingly available to children in low-resource settings, attention to adherence will be just as important. Furthermore, various programmatic issues cause barriers to optimal adherence to treatment, and may have to be addressed.

16.4. Challenges

Adherence in children is a special challenge because of factors relating to children, caregivers, medications, and the interrelationships of these factors. The limited number of paediatric formulations, poor palatability, high pill burden or liquid volume, frequent dosing requirements, dietary restrictions and side-effects may hamper the regular intake of required medications. Furthermore, the successful treatment of a child requires the commitment and involvement of a responsible caregiver. This may be particularly complicated if the family unit is disrupted as a consequence of adverse health or economic conditions. Mothers of HIV-infected children are very often HIV-infected themselves. As a result, the care of the child may be less than optimal because of the mother's compromised health. It is preferable that a secondary (back-up) informed caregiver be involved in the care of an HIV-infected child. In addition, caregivers are often concerned with the disclosure of HIV status to family members, friends or school teachers, thus restricting the child's options for seeking support. Finally, an understanding of how the developmental stage of the child influences the extent to which he or she will cooperate with the regular administration of medicine helps to guide planning and support for the process.

16.4.1. Maximizing adherence

Efforts to support and maximize adherence should begin before the initiation of treatment [210]. The development of an adherence plan and education of the child and their caregivers are important first steps. Initial patient education should cover basic information about HIV and its natural history, the benefits and side-effects of ARV medications, how the medications should be taken and the importance of not missing any doses. If medication is mixed with food or dispersed in water, all the food or water must be taken in order to ensure administration of the full dose. Especially for young children, additional elements may be necessary, including practising the measurement and administration of liquids with caregivers and training children in how to swallow pills. When choosing regimens, policymakers, programmers and providers should consider ways to minimize the number of pills, the volumes of liquids and the number of doses. Regimens that avoid food restrictions and that can be dosed using FDCs, blister packs or other child-friendly formulations should be used whenever possible. Fitting the ARVs into the child's (and/or caregiver's) lifestyle or, where possible and appropriate, matching drug regimens for children to regimens of adults in the same family, as well as preparedness for common, non-severe adverse effects, may facilitate successful adherence.

Adherence during the first days and weeks of treatment can be critical to the long-term success of a regimen, particularly for some ART combinations with a higher risk of development of resistance. Where children stop ARV drugs within first-line regimens (either intentionally or unintentionally), it should be recognized that NNRTI components have half-lives that are several days to weeks longer than the half-lives of NRTI components. Therefore, sudden interruption of first-line therapy may result in the persistence of subtherapeutic NNRTI drug levels which can lead to the premature development of NNRTI drug-resistant virus. Emphasizing the need to consistently take all the ARV drugs is therefore particularly important with an NNRTI/NRTI-based first-line regimen. An uninterrupted ARV supply at both facility and household level is clearly essential.

Continuous assessment of and support for adherence are vital components of a proactive approach to ART. The assessment of adherence should be a concern of every health-care provider participating in the care of infants and children. Adherence assessment should be performed whenever there is a visit to a health centre in order to identify children and caregivers in need of the greatest adherence support.

16.4.2. Measuring and evaluation

The measurement of adherence may be particularly difficult in children. Quantitative methods are generally employed (asking children or caregivers how many doses of medication have been missed during the past 3, 7 or 30 days) but the responses may not reflect true adherence as children and caregivers learn the social desirability of reporting complete adherence. Reviews of pharmacy records as well as pill counts can provide valuable information about adherence. Measurement of VL can be used to assess adherence to medication but this is unlikely to be widely available in resource-limited settings at present.

Qualitative evaluations of adherence can more effectively identify barriers to optimal medication-taking but can be more difficult and time-consuming for health-care providers as well as children and/or their caregivers. These evaluations focus on obtaining descriptions of impediments to adherence or problems encountered. Furthermore, the assessment of adherence can be complicated by diverging reports between children and caregivers, as well as by the limited availability of information when the caregivers bringing children to clinics are not the ones responsible for supervising ART administration [211].

16.4.3. Ongoing support

In addition to the assessment of adherence, ongoing support for adherence is a vital component of successful treatment [207]. Practical aids can be helpful, including the use of calendars, pillboxes, blister packs and labelled syringes. Directly observed therapy (DOT) and the use of treatment buddies or partners have been successful in some settings, but such strategies have not been widely studied in the paediatric population. Community and psychological support can be critical for caregivers as well as children and peer support groups may be particularly beneficial for mothers with young children on ART. Adherence may vary with time: families may have periods when adherence is excellent and other periods when it fails, often because of changing life circumstances. Adherence may also suffer as the child responds to therapy, health improves and the impetus to take daily medication decreases.

16.5. Programmatic issues

Programmatic issues can affect paediatric adherence and must be considered as programmes expand to scale up paediatric ART. Problems with adherence in children, their caregivers and adolescents (in particular, those who are in transition of care) should be anticipated; they are encountered at every level of the health-care system involved in providing ART. Continuous access to a supply of free ARV drugs as well as the development of well-functioning systems for forecasting, procurement and supply management are essential components of paediatric treatment programmes. The limited formulations currently available for children present significant barriers to optimal adherence. The development of formulations appropriate for use in infants and young children is strongly encouraged.

Copyright © 2010, World Health Organization.

All rights reserved. Publications of the World Health Organization can be obtained from WHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel.: +41 22 791 3264; fax: +41 22 791 4857; e-mail: tni.ohw@sredrokoob). Requests for permission to reproduce or translate WHO publications – whether for sale or for noncommercial distribution – should be addressed to WHO Press, at the above address (fax: +41 22 791 4806; e-mail: tni.ohw@snoissimrep).

Bookshelf ID: NBK138573

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