What Should we do When HIV-Positive Children Fail First-Line Combination Antiretroviral Therapy? A Comparison of 4 ART Management Strategies

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Abstract

Background:

Managing virologic failure (VF) in HIV-infected children is especially difficult in resource-limited settings, given limited availability of alternative drugs, concerns around adherence and the development of HIV resistance mutations. We aimed to evaluate four management strategies for children following their first episode of VF by comparing their immunologic and virologic outcomes.

Methods:

We included children (aged <16 years) with VF from 8 IeDEA-SA cohorts, initiating cART between 2004-2010, who followed one of four management strategies: continuing on their failing regimen; switching to a second-line regimen; switching to a holding regimen (either lamivudine monotherapy or other non-cART regimen); discontinuing all ART. We compared the effect of management strategy on the 52-week change in CD4% and log10VL from VF, using inverse probability weighting of marginal structural linear models.

Results:

982 patients were followed over 54168 weeks. Relative to remaining on a failing regimen, switching to second-line showed improved immunologic and virologic responses 52 weeks after VF with gains in CD4% of 1.5% (95% CI 0.2-2.8) and declines in log10VL of -1.4 copies/mL (95% CI -2.0, -0.8), whilst switching to holding regimens or discontinuing treatment had worse immunologic (-5.4% (95% CI -12.1, 1.3) and -5.6% (95% CI -15.4, 4.1)) and virologic outcomes (0.2 (95% CI -3.6, 4.1) and 0.8 (95% CI -0.6, 2.1) respectively.

Conclusions:

The results provide useful guidance for managing children with VF. Consideration should be given to switching children failing first-line cART to second-line, given the improved virologic and immune responses when compared with other strategies.

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