The international medical humanitarian organization, Doctors without Borders/Médecins Sans Frontières (MSF) criticized pharmaceutical companies for their delays and failure to develop appropriate formulations of HIV medicines for children. As WHO recommends that all children diagnosed with HIV should immediately start antiretroviral therapy.1. But without optimal paediatric HIV drug formulations, countries will continue to struggle to implement this recommendation

WHO recommendation2: The increasing levels of pretreatment antiretroviral (ARV) drug resistance documented in low and middle-income countries prompted WHO to issue guidelines recommending that countries with pretreatment resistance to efavirenz or nevirapine at or above 10% should urgently consider revising their first-line regimens.

Population First line drug Second line drug Third line drug
Children Two NRTIs + DTG/RAL Two NRTIs + (ATV/r or LPV/r) DRV/r + DTG + 1-2 NRTIs (if possible, consider optimization using genotyping)
Two NRTIs + LPV/r Two NRTIs + DTG
Two NRTIs + NNRTI Two NRTIs + DTG

Nucleoside reverse-transcriptase inhibitors (NRTIs), dolutegravir (DTG), raltegravir (RAL), lopinavir/ ritonavir (LPV/r), non-nucleoside reverse-transcriptase inhibitor (NNRTI), atazanavir/ritonavir (ATV/r), Darunavir/ritonavir (DRV/r).

Note –

  • ATV/r can be used as an alternative to LPV/r among children older than three months, but the limited availability of suitable formulations for children younger than six years, the lack of a fixed-dose formulation and the need for separate administration of a ritonavir booster should be considered when choosing this regimen.
  • This applies to children for whom approved DTG dosing is available.
  • RAL should remain the preferred second-line regimen for the children for whom approved DTG dosing is not available. and may be recommended as a preferred first-line regimen for neonates (conditional recommendation)
  • ATV/r or LPV/r should remain the preferred second-line treatment for the children for whom approved DTG dosing is not available.
  • Children younger than three years should not use DRV/r.

Paediatric HIV remains a neglected disease, and the small market for paediatric HIV medicines means they have never been a priority for either multi-national pharmaceutical corporations or generic manufacturers. Delays have plagued both the development and introduction of newer paediatric drug formulations, and scale-up of existing formulations. For example:

  • DTG approved for children older than six years is still not available for children because pharmaceutical corporation ViiV Healthcare is yet to finalize necessary studies and register a dispersible tablet formulation for younger children.
  • RAL has now been approved for use from birth, providing additional options for neonates and children living with HIV. A paediatric granule formulation of RAL, already exists, but pharmaceutical corporation Merck has been slow to register it in developing countries.
  • The LPV/r paediatric formulation currently supplied by generics manufacturers Mylan and Cipla, has also been plagued with problems of its slow supply and higher price compared to the harsh-tasting lopinavir/ritonavir syrup, which supposed to be replaced by their products.

Note –These are new WHO interim guideline / recommendations regarding preferred first-line regimens for children initiating ART, which now include DTG and RAL. WHO also recommends active toxicity surveillance of emerging toxicity issues of DTG and other new ARV drugs.

Footnotes

1. https://www.msfindia.in/hivaids-pharmaceutical-corporations-failing-children-hiv

2. http://apps.who.int/iris/bitstream/handle/10665/273632/WHO-CDS-HIV-18.18-eng.pdf

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