This study aims to find out whether treating children and young people living with HIV with two anti HIV medicines, dolutegravir and lamivudine, is safe and as effective as the three-medicine anti-HIV treatments currently used in routine practice.

This study will include 370 children and young people aged 2 to less than 15 years old who are living with HIV and are being treated with anti-HIV medicines for the first time. Participants will be split into two groups, by chance, by a process called "randomisation". One group will continue to receive the anti-HIV medicines already taken according to country-specific routine practice. The second group will change to the new combination of medicine, dolutegravir and lamivudine (with the combination written usually as "DTG/3TC"). Depending on the weight, participants in the second group will be able take the new medicine either as one tablet a day or as a small number of dispersible tablets that are also taken once a day. All children and young people in the study will have regular clinic assessments that are at a similar frequency to the clinic visits that participants would have outside of the study. Blood tests will be performed to check that the medicine is safe and, at some visits, participants and their carers will also be asked to answer some questions on how they feel about taking their medicine. All children and young people will be followed until the last participant who joins the study has been in the study for 96 weeks.

After 96 weeks, children who were randomised to the DTG/3TC arm will enter the extended follow-up continuing to receive DTG/3TC.

Inclusion Criteria for the Main trial:

1. HIV-1 infected children who are virologically suppressed for at least the last 6 months prior to enrolment
2. Aged 2 to <15 years old
3. Weight 6 kg or higher
4. Children on the same triple-drug PI/r, NNRTI or INSTI containing ART regimen for at least 3 months
5. Girls who have reached menarche must have a negative pregnancy test at screening and randomisation
6. Girls who are sexually active must be willing to adhere to highly effective methods of contraception
7. A parent or legal guardian is willing and able to give informed consent on behalf of the child as per national legislation and willing to adhere to the protocol
8. Participant is willing to give informed assent if the trial site clinician deems them old enough and able to understand the age-appropriate information about participation in the study

Inclusion Criteria for the Extended Follow up:

1. Participants remain on DTG/3TC at the end of the randomised phase, and in the opinion of the treating physician, derive ongoing benefit from DTG/3TC
2. Participants have no access to weight-appropriate DTG/3TC formulation via their national programme

Exclusion Criteria for the Main trial :

1. Any previous switch in ART regimen for virological, immunological or clinical treatment failure
2. Any changes in ART in the last 6 months for reasons other than due to child's growth, drug stock-outs, changes in country guidelines and treatment simplification
3. Evidence of previous resistance to 3TC or INSTI
4. Any prior use of regimens consisting of single or dual NRTIs with the exception of a course of zidovudine for PMTCT
5. Known allergy or contraindications to dolutegravir or lamivudine
6. Diagnosis of tuberculosis and on anti-tuberculosis treatment; children can be enrolled after successful tuberculosis treatment
7. Treatment of co-morbidities with drugs which have significant interactions with antiretroviral treatment, requiring dose adjustment of the study drugs (children can be enrolled after the illness resolves)
8. Randomisation visit more than 12 weeks after the most recent screening visit
9. Evidence of hepatitis B infection with no protective immunity against hepatitis B: participants positive for HBsAg or HBcAb and negative for HBsAb
10. Anticipated need for hepatitis C virus therapy with interferon-based regimen prior to the primary endpoint.
11. Screening ALT equal to 3 or more times the upper limit of normal AND bilirubin equal to 2 or more times the upper limit of normal (ALT ≥3xULN AND bilirubin ≥2xULN)
12. Screening ALT equal to 5 or more times the upper limit of normal ALT (≥5xULN)
13. 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), or known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
14. Screening creatinine clearance <50 mL/min/1.73m2
15. Patients aged ≥6 years at moderate or high risk of suicide as determined by Columbia-Suicide Severity Rating Scale (C-SSRS)
16. Girls who are pregnant or breastfeeding
17. Children who are in the legal custody of the State and do not have a parent or guardian able to provide informed consent on their behalf.