HIV Infections and Infestations
Conditions
Interventions
Current interventions as of 07/04/2020:
Control group: Control group is continuous combination ART consisting of dolutegravir, with a tenofovir and lamivudine/emtricitabine backbone
Experimental gro
Sponsors
University College London
Eligibility
Sex/Gender
All
Age
12 Years to 19 Years
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 07/04/2020: 1. HIV-1-infected 2. Aged 12-19 years 3. Aware of HIV status 4. On ART for =1 year, with no previous regimen change for treatment failure 5. On ART consisting of DTG, tenofovir and lamivudine/emtricitabine for =1 month prior to screening 6. Virologically suppressed with all HIV-1 RNA viral loads < 50copies/ml* in the last 12 months up to and including screening. Additionally there must be one result < 50copies/ml* at least 12 months prior to screening and the viral load at trial screening must be < 50 copies/ml* 7. Girls who are sexually active must be willing to adhere to highly effective methods of contraception** 8. Written informed consent/assent provided by participant (if aged 18 to 19 years) and/or carer/legal guardian (if participate aged 12 to 17 years) as appropriate 9. Written informed assent in participates aged 12 to 17 years *VL <100 copies/ml is allowed for diluted samples with maximum dilution 1:5, except for the screening sample where the VL must be < 50 copies/ml in an undiluted sample **Highly effective contraception are injectable, implantable, oral and intrauterine contraceptives which have an expected failure rate <1% per year ______ Previous inclusion criteria: 1. HIV-1-infected 2. Aged 12-19 years 3. Aware of HIV status 4. On ART consisting of 2NRTI and a third agent (with no previous regimen change for treatment failure) 5. On ART for =1 year 6. On DTG-based ART for =1 month prior to screening 7. Virologically suppressed with all HIV-1 RNA viral loads <50copies/mL* in the last 12 months up to and including screening. Additionally there must be one result <50copies/ml* at least 12 months prior to screening and the viral load at trial screening must be <50 copies/mL 9. Written informed consent/assent provided by participant and/or carer/legal guardian as appropriate *VL <100 copies/ml is allowed for diluted samples with maximum dilution 1:5, except for the screening sample where the VL must be <50 copies/ml in an undiluted sample
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 07/04/2020: 1. Females who are pregnant or breastfeeding 2. Females who plan to become pregnant during the trial follow-up or are unwilling to use a highly effective method of contraception** for the duration of the trial if sexually active 3. Moderate or High risk score on the Columbia-Suicide Severity Rating Scale 4. On treatment for any active TB 5. Contraindication to continued receipt of dolutegravir or any formulation of tenofovir, emtricitabine/lamivudine 6. Underlying medical condition that in the opinion of the Investigator precludes participation 7. Previous randomisation in the LATA trial **Highly effective contraception are injectable, implantable, oral and intrauterine contraceptives which have an expected failure rate <1% per year _____ Previous exclusion criteria: 1. Females who are pregnant or breastfeeding 2. Females who plan to become pregnant during the trial follow-up or are unwilling to avoid pregnancy* for 96 weeks 3. Moderate or High risk score on the Columbia-Suicide Severity Rating Scale ** 4. On treatment for any active TB 5. Contraindication to receipt of dolutegravir, any formulation of tenofovir, emtricitabine/lamivudine 6. Previous randomisation in the LATA trial *methods of avoiding pregnancy include the following: use depot or implant hormonal contraception, oral contraception or intrauterine device. **Participants initially ineligible on the basis of a moderate or high risk score on the Columbia-Suicide Severity Rating Scale if in the opinion of the Investigator it is safe for them to be rescreened
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Current primary outcome measure as of 07/04/2020: The proportion of participants with confirmed virological rebound, defined as the first of 2 consecutive plasma HIV-RNA =50 copies/mL at any time up to the 96-week assessment _____ Previous primary outcome measure: Incidence of confirmed virological rebound, defined as 2 consecutive plasma HIV-RNA =50 copies/mL at any time up to the 96-week assessment | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 07/04/2020: 1. Efficacy: 1.1. Proportion of participants with HIV-RNA =50 copies/mL at 48 and 96 weeks using the FDA snapshot algorithm 1.2. Proportion of participants with HIV-RNA =1000 copies/mL (confirmed) by week 96 1.3. The number and type of HIV mutations at confirmed virological rebound 1.4 HIV-RNA <50 copies/mL and no switch to second-line ART for treatment failure at 24, 48, 64 and 96 weeks 2. Safety: 2.1. Change in toxicity profile including change in metabolic parameters (lipids, HbA1C, phosphate), renal function (eGFR) from baseline to 96 weeks; change in anthropometric measures from baseline to 48 and 96 weeks 2.2. Time to any new or recurrent WHO grade 3 or WHO grade 4 event or death 2.3. Incidence of serious, grade 3 and 4, and treatment-modifying grade 1-2 adverse events 2.4. The proportion of participants with any change from baseline ART regimen 2.5. Change in CD4+ and CD8+ T-cell count from baseline to 48 and 96 weeks 3. Patient-reported outcomes: 3.1. Adherence, acceptability, well-being, and neuropsychiatric problems (e.g. depression, anxiety and sleep disturbance) 3.2. Healthcare resource utilisation (as a sub-study outcome) 3.3. Health-related quality-of-life (as a sub-study outcome) _____ Previous secondary outcome measures: 1. Efficacy 1.1. Proportion of participants with HIV-RNA =50 copies/mL at 48 and 96 weeks using the FDA snapshot algorithm 1.2. Proportion of participants with HIV-RNA =1000 copies/mL (confirmed) by week 96 1.3. The number and type of HIV mutations at confirmed virological rebound 1.4 HIV-RNA <50 copies/mL and no switch to second-line ART for treatment failure at 24, 48, 64 and 96 weeks 2. Safety 2.1. Change in toxicity profile including change in metabolic parameters (lipids, HbA1C, phosphate), renal function (eGFR) from baseline to 96 weeks; change in anthropometric measures from baseline to 48 and 96 weeks 2.2. Incidence of clinical events (WHO 3 and 4 events; death) 2 | — |
Countries
Kenya, South Africa, Uganda, Zimbabwe
Outcome results
None listed