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Table 1 Participant Inclusion and Exclusion Criteria from Protocol Version 4.0 onwards

From: ODYSSEY clinical trial design: a randomised global study to evaluate the efficacy and safety of dolutegravir-based antiretroviral therapy in HIV-positive children, with nested pharmacokinetic sub-studies to evaluate pragmatic WHO-weight-band based dolutegravir dosing

Inclusion Criteria:
All • Children ≥28 days and < 18 years weighing ≥3 kg with confirmed HIV-1 infectiona
• Parents/carers and children, where applicable, give informed written consent
• Girls who have reached menses must have a negative pregnancy test at screening and randomisation and be willing to adhere to effective methods of contraception if sexually active
• Children with co-infections who need to start antiretroviral therapy can be enrolled according to local/national guidelines
• Parents/carers and children, where applicable, willing to adhere to a minimum of 96 weeks’ follow-up
ODYSSEY A (First-line) only • Planning to start first-line antiretroviral therapy
ODYSSEY B (Second-line) only • Planning to start second-line antiretroviral therapy defined as either: (i) switch of at least 2 antiretroviral therapy drugs due to treatment failure; or (ii) switch of only the third agent due to treatment failure where drug sensitivity tests show no mutations conferring nucleos(t) ide reverse transcriptase inhibitors resistance
• Treated with only one previous antiretroviral therapy regimen. Single drug substitutions for toxicity, simplification, changes in national guidelines or drug availability are allowed
• At least one nucleos(t) ide reverse transcriptase inhibitor with predicted preserved activity available for a background regimen
• In settings where resistance tests are routinely available, at least one active nucleos(t) ide reverse transcriptase inhibitor from TDF/TAF, ABC or ZDV should have preserved activity based on cumulative results of resistance tests
• In settings where resistance tests are not routinely available, children who are due to switch according to national guidelines should have at least one new nucleos(t) ide reverse transcriptase inhibitor predicted to be available from TDF/TAF, ABC or ZDV
• Viral load ≥500 c/ml at screening visit or within 4 weeks prior to screening‡
Exclusion Criteria:
All • History or presence of known allergy or contraindications to dolutegravir
• History or presence of known allergy or contraindications to proposed available nucleos(t) ide reverse transcriptase inhibitor backbone or proposed available standard-of-care third agent.
• Alanine aminotransferase (ALT) ≥5 times the upper limit of normal (ULN), OR ALT ≥3xULN and bilirubin ≥2xULN
• Patients with severe hepatic impairment or unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, or persistent jaundice), known biliary abnormalities (with the exception of Gilbert’s syndrome or asymptomatic gallstones)
• Anticipated need for Hepatitis C virus therapy during the study
• Pregnancy or breastfeeding
• Evidence of lack of susceptibility to integrase inhibitors or more than a 2-week exposure to antiretrovirals of this class
  1. a Recruitment of ART naive children ≥35 kg was capped in Jul 2017. Recruitment opened in children ≥6 years and < 18 years weighing ≥20 kg (Protocol version 2.0). Protocol version 3.0 included recruitment of children ≥14 kg (with no age restriction) with a lead-in PK sub-study for children weighing 14 to < 20 kg (children weighing 14-15 kg had to be willing to enter the lead-in PK sub-study to enrol in the trial). Protocol version 4.0 onwards allows allowed for the recruitment of children ≥3 kg and ≥ 28 days, children weighing 3 to < 14 kg had to be willing to participate in a lead-in PK sub-study to enter the trial. Throughout the trial eligibility was based in both arms on availability of DTG dose given age/weight-band. ‡ Protocol version 3.0 onwards (viral load ≥1000 c/ml in protocol version 2.0)
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