Tackling virological failure in HIV-infected children living in Africa

Abstract

Drug resistance in HIV-infected children is one of the main contributors to antiretroviral treatment (ART) failure, especially in developing countries. Sub-Saharan Africa has the largest burden of pediatric HIV infection in the world. Herein, we systematically review the current status of ART failure in HIV-infected African children. A literature search for publications within 10 years was performed through PubMed to identify relevant articles. Included studies examined the impact of timing of ART initiation, criteria for diagnosing therapeutic failure, predictors of therapeutic failure, management strategies and future directions to minimize failure rates in these pediatric populations. Although there is scale-up of ART programs in Africa, novel therapeutic and management strategies are needed to overcome current challenges.

Keywords:

• Africa
• antiretroviral treatment
• children
• HIV
• resistance

Acknowledgements

The authors thank participants to GIP-ESTHER (Ensemble pour une Solidarité Thérapeutique Hospitalière En Réseau) France – Central African Republic for helpful discussions.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Current WHO guidelines suggest antiretroviral therapy (ART) for all children aged <5 years.

• Nevirapine given for prevention of mother-to-child transmission may result in direct transmission of HIV drug-resistant virus; a boosted protease inhibitor-based regimen is recommended as first-line therapy by all pediatric guidelines for children at high risk of NNRTI resistance.

• ART failure rates in African children may reach 60% in some countries and exceed failure rates observed in adults

• Poor adherence is associated with ART failure and is encouraged by social stigma.

• The cost of viral load testing precludes routine monitoring of viral loads in many regions in Africa.

• In Africa, CD4 cell count measurement remains the central laboratory test for monitoring HIV disease progression, evaluating response to ART and guiding decision making. However, CD4 count is not consistently an accurate predictor of ART failure in children receiving treatment.

• Current WHO criteria for identifying immunological failure are frequently unable to identify children failing ART in resource-limited settings.

• Many HIV-infected children are malnourished, which negatively impacts the immune system.