1. P1060 commentary Philippa Musoke MBChB Makerere University –Johns Hopkins University Research Collaboration, Kampala Uganda

2. Cohort 1 NVP exposed infants with higher treatment failure rates on a NVP based regimen NVP exposed infants with higher treatment failure rates on a NVP based regimen Emergence of NVP resistance after sd NVP Emergence of NVP resistance after sd NVP There are higher rates of NNRTI resistance after prolonged NVP prophylaxis There are higher rates of NNRTI resistance after prolonged NVP prophylaxis Recommendation Recommendation Children below 2 years of age Children below 2 years of age PI as 1 st line therapy should be the standard of care BUT PI as 1 st line therapy should be the standard of care BUT Option for use of NVP where PIs unavailable Option for use of NVP where PIs unavailable Children > 2 years Children > 2 years NVP based regimen as 1 st line regimen NVP based regimen as 1 st line regimen

3. Challenge of 1 st line PI regimen in NVP exposed children Large numbers of NVP exposed children expected Large numbers of NVP exposed children expected Can all countries afford scale up of PI based 1 st line ART ? Can all countries afford scale up of PI based 1 st line ART ? If PMTCT coverage is high then If PMTCT coverage is high then Fewer HIV infected children but.. Fewer HIV infected children but.. Implementation of PI based regimens – more complex Implementation of PI based regimens – more complex Syrup requires refrigeration Syrup requires refrigeration Tablet 100mg ( Alluvia) can not be cut in half Tablet 100mg ( Alluvia) can not be cut in half Lack of a fixed dose combination Lack of a fixed dose combination More expensive than NNRTIs More expensive than NNRTIs Not widely available in many resource limited settings Not widely available in many resource limited settings Protease Inhibitors need to be made available for these children

4. Cohort II NVP unexposed - baseline NNRTI resistance should not be an issue NVP unexposed - baseline NNRTI resistance should not be an issue Previous studies have shown treatment success with NVP > 70 % virological success at 24 – 48 wks Previous studies have shown treatment success with NVP > 70 % virological success at 24 – 48 wks P1060 NVP arm, had higher treatment failure P1060 NVP arm, had higher treatment failure Adherence to syrups vs FDC ? Adherence to syrups vs FDC ? Lead in phase of NVP - emergence of resist. ? Lead in phase of NVP - emergence of resist. ? Subtype C – higher rates of NNRTI resistance ? Subtype C – higher rates of NNRTI resistance ?

5. Challenge of implementation of PI in non exposed children Implementation of PI based regimen for all HIV infected children under 2 years Implementation of PI based regimen for all HIV infected children under 2 years This may be feasible for some RLS – S Africa This may be feasible for some RLS – S Africa May not as feasible other countries May not as feasible other countries Zimbabwe ?, Malawi ?, Tanzania ?, Uganda ? Zimbabwe ?, Malawi ?, Tanzania ?, Uganda ? There should be an option for children NOT exposed to NVP to initiate a NVP based regimen There should be an option for children NOT exposed to NVP to initiate a NVP based regimen Need to ensure good adherence and close monitoring Need to ensure good adherence and close monitoring Not easy to detect early treatment failure without access to viral loads Not easy to detect early treatment failure without access to viral loads

6. Immune response and Growth Wide scale implementation of PI in infants may affect future growth of these infected children Wide scale implementation of PI in infants may affect future growth of these infected children Critical issue in view of the high rates of malnutrition and food insecurity Critical issue in view of the high rates of malnutrition and food insecurity Do the children gain weight more slowly but catch up over time ? Do the children gain weight more slowly but catch up over time ? Needs further follow up ( Version 5.0) Needs further follow up ( Version 5.0)

7. Summary NVP exposed HIV infected children NVP exposed HIV infected children Every effort should be made to make PIs available for these children Every effort should be made to make PIs available for these children Development of FDC of AZT/3TC/LPV/r a priority, if we are to scale up early initiation of ART Development of FDC of AZT/3TC/LPV/r a priority, if we are to scale up early initiation of ART Where there are no PIs children should not be denied ART Where there are no PIs children should not be denied ART Non-exposed HIV infected children Non-exposed HIV infected children Where PIs are available they may be used BUT Where PIs are available they may be used BUT NVP based 1 st line regimen should still remain an option for this group of children ( 60% had treatment success) NVP based 1 st line regimen should still remain an option for this group of children ( 60% had treatment success) However, some may feel it is easier to have one 1 st line regimen for all infants BUT $$$$$$ However, some may feel it is easier to have one 1 st line regimen for all infants BUT $$$$$$