17.1. Principles

• Strategies that balance benefits and risks for children need to be explored in the event of second-line treatment failure.
• For older children who have more therapeutic options available to them, it may be possible to construct third-line ARV regimens using novel drugs used in the treatment of adults such as darunavir and raltegravir.
• Children on a failing second-line regimen with no new ARV options should continue with a tolerated regimen.
• When stopping ART may have to be considered, the prevention of OIs, relief of symptoms and management of pain needs to continue.

17.2. Background

Multidrug resistance in children who have received multiple ARV regimens is an increasing problem. Limited data are available on which to base recommendations about treatment options. The objective of treatment should be to maintain CD4 values,ⁱ reduce adverse reactions and enhance the prevention of OIs. If children have end-stage HIV disease and no further suitable ARVs are available, stopping ART and keeping them comfortable with symptom-based care may have to be considered.

17.3. Considerations for the use of ARV salvage regimens

A number of treatment approaches have been considered in clinical trial settings, mainly in adults and where VL monitoring and resistance testing is possible. These approaches include the addition or substitution of new drugs (such as enfuvirtide/T20), mega-HAART (combination of five or more drugs, including two or more PIs), strategic recycling of drugs, structured treatment interruptions (STIs) and continuation of current therapy until additional drugs become available. An analysis of 13 HIV cohorts involving adult patients who had three-class virological failure indicates that achieving and maintaining an absolute CD4 count above 200 cells/mm³ becomes the primary aim. Treatment regimens that achieve suppression of viral load below 10 000 copies per ml may be associated with better maintenance of CD4 levels [212]. Immunological and clinical benefits have been reported even among patients who have partial virological response or virological rebound, presumably as a result of decreased viral fitness attributable to the presence of multiple resistance mutations. Studies in adults suggest therapeutic benefit from NRTI treatment in the presence of drug-resistant HIV [130, 132, 213-217]. Decisions about therapy in such situations are complex and require, at a minimum, consultation with an HIV specialist.

17.4. Considerations for palliative care and stopping ART

The prevention of OIs, relief of symptoms and management of pain need to continue, even when the option to stop ART may have to be considered. Symptoms and pain are a major cause of discomfort and poor quality of life during the course of HIV infection in infants and children. Many of these symptoms can be prevented, treated or controlled with basic medications and therapies. Non-pharmacological methods are an important adjuvant to symptom management. Efforts to identify the cause of symptoms and pain should be pursued as much as possible, without adversely affecting the quality of the child's life and within the limits of available resources. Symptoms and related pain should be anticipated and prevented to the extent possible.

The care of the terminally ill child is a particular challenge in resource-limited settings because there are few replicable models of planned terminal care, both institutional and community-based [218]. At the end of life, there are typically more symptoms that must be addressed, and the child may need to take multiple drugs to control and treat a variety of symptoms and conditions. Terminal care preparation for children and their families is a long-term process and requires continuity of care providers and services.

Critical factors in effective long-term planning include early and active communication with and involvement of parents/guardians/caregivers and their ongoing support, community-level support structures, a functional health infrastructure, knowledgeable human resources, and access to essential drugs and supplies. Terminally ill children are often placed in acute care facilities that may not be appropriate for their needs. Few resource-limited settings have inpatient facilities for terminal care, and home-based care is usually preferred. Families must be involved in decisions about the best place for care and the preferred place of death if children have end-stage HIV disease.

Footnotes

i

Where virological monitoring is available, maintenance of low VL may be included in the strategies.