HIV/AIDS
Conditions
Interventions
DTG and 3TC
Standard of care
Sponsors
Fondazione Penta Onlus Penta
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. HIV-1 infected children who are virologically suppressed for at least the last 6 months prior to enrolmenta,b 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 contraceptionc 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
Exclusion criteria
Exclusion criteria: 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 INSTIa 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 treatmentb 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 d 15. Patients aged =6 years at moderate or high risk of suicide as determined by Columbia-Suicide Severity Rating Scale (C-SSRS) e 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of children with confirmed viral rebound (defined as the first of two consecutive HIV-1 RNA =50c/mL) by week 96 | — |
Secondary
| Measure | Time frame |
|---|---|
| Proportion of children with confirmed viral rebound (defined as the first of two consecutive HIV-1 RNA =50c/mL) by week 48 Proportion of children with confirmed HIV-1 RNA =50c/mL at weeks 48 and 96 (modified FDA snapshot) Proportion of children with HIV-1 RNA =50c/mL at weeks 24, 48 and 96 (including blips and confirmed measures =50c/mL) New resistance-associated mutations in those with confirmed HIV-1 RNA =50c/mL Time to any new or recurrent WHO 3 or WHO 4 event or death Change in CD4 (absolute and percentage) from baseline to weeks 24, 48 and 96;Secondary Safety Outcome Measures- Incidence of serious adverse events, grade 3 and 4 clinical and laboratory adverse events Incidence of adverse events leading to discontinuation or modification of the treatment regimen Proportion of children with a change in ART for toxicity or switch to second-line Change in blood lipids from baseline to weeks 48 and 96 Change in creatinine clearance estimated using bedside-Schwartz to weeks 48 and 96;Patient-reported outcome measures - Adherence as assessed by participant/care-giver questionnaires Acceptability, sleep and mood, suicidal ideation and health-related quality of life as assessed by participant/care-giver completed questionnaires | — |
Countries
South Africa
Contacts
Public ContactFatima Mayat
Director Phru
Outcome results
None listed