A randomised trial of dolutegravir (DTG)-based antiretroviral treatment vs standard of care (SOC) in children with HIV infection starting first treatment or switching to second-line antiretrovirals.

Recruitment & Eligibility

Status: A

Sex: All

Target Recruitment: 700

Inclusion Criteria

- Children <18 years weighing =14kg with confirmed HIV-1 infection and DTG dose known for child's weight-band*.
- 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 ART according to local/national guidelines.
- Parents/carers and children, where applicable, willing to adhere to a minimum of 96 weeks' follow-up.

*Children weighing 14 to <20kg must be eligible and willing to participate in the Weight band (WB)-PK1 substudy unless enrolment for this weight band directly into the main trial has opened following the WB-PK1 substudy or dosing information has become available from the IMPAACT P1093 DTG dose-finding study.

Additional criteria for ODYSSEY A:
- Planning to start first-line ART

Additional criteria for ODYSSEY B:
- Planning to start second-line ART defined as either: (i) switch of at least 2 ART 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 NRTI resistance.
- Treated with only one previous ART regimen. Single drug substitutions for toxicity, or simplification, changes in national guidelines or drug availability are allowed.
- At least one NRTI with predicted preserved activity available for a background regimen.
- In settings where resistance tests are routinely available, at least one active NRTI from tenofovir, abacavir or zidovudine 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 NRTI available from tenofovir, abacavir or zidovudine
- Viral load =500 c/ml at screening visit or within 4 weeks prior to screening
Are the trial subjects under 18? yes
Number of subjects for this age range: 700
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range 0
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion Criteria

History or presence of known allergy or contraindications to DTG.
History or presence of known allergy or contraindications to proposed available NRTI backbone or proposed available SOC 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 (HCV) 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.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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