HIV-1 infected individuals currently taking an INSTI-based three-drug first-line regimen for less than 18 months and who have been virologically suppressed with HIV-1 RNA <50 copies/mL MedDRA version: 20.1 Level: LLT Classification code 10068341 Term: HIV-1 infection System Organ Class: 100000004862
Conditions
Interventions
Trade Name: Dovato
Product Name: DOVATO
Product Code: [DTG/3TC]
Pharmaceutical Form: Film-coated tablet
Current Sponsor code: DTG/3TC
Other descriptive name: dolutegravir (DTG) plus lamivudine (3TC)
C
Sponsors
SOCIETA' ITALIANA MALATTIE INFETTIVE E TROPICALI
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • HIV-1 documented infection • Age >=18 years • To be treated as ART naïve for overall less than 18 months before screening • To receive a stable (not changed) INSTI-based first-line three-drug ART (see Target Population section for regimens allowed); switch between different NRTIs are allowed • To have reached a HIV-1 RNA =50 copies (cp)/mL) • No known allergy or intolerance to NRTIs, or INSTIs • Being able to comply with the protocol requirements • Informed consent signed Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 300 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 140
Exclusion criteria
Exclusion criteria: Having failed virologically • Having changed the INSTI drug • Any major INSTI- or NRTI-resistance-associated mutation documented before starting ART Pregnancy or breast-feeding • HBsAg positivity • HCV-RNA positivity needing for any hepatitis C virus (HCV) therapy during the study • An active malignancy or opportunistic infection requiring active treatment or primary prophylaxis • Women of childbearing potential not adopting an effective birth control system throughout the study period • Creatinine clearance of <50 mL/min/1.73m2 via CKD-EPI method • A life expectancy <2 years • Use of HIV immunotherapeutic vaccines; other experimental agents, ART drugs not otherwise specified in the protocol, cytotoxic chemotherapy, systemically administered immunomodulators • Individuals who in the investigator’s judgment, poses a significant suicidality risk; • Major Depression, Bipolar Disorders and Psychoses
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate efficacy and safety of an early switch to a two-drug regimen with DTG/3TC as single pill in participants who achieved and maintained a recent (less than 1 year) virological suppression with a three-drug INSTI-based ART, compared to continuing the INSTI-based three-drug first-line regimen. The primary analysis will be performed on the intention-to-treat (ITT) population as the proportion of participants with virologic rebound (one HIV-1 RNA ¿50 copies/mL) at Week 48 as defined by the US Food and Drug Administration (FDA) snapshot algorithm (non-inferiority margin 4%). An exploratory interim analysis will be performed after 50% of participants have completed 24 weeks of follow-up. After 48 weeks all the participants actively followed in the control group will switch to DTG/3TC as single pill (delayed switch), and the final evaluation will be performed after 96 weeks.;Secondary Objective: To evaluate safety and tolerability of the two strategies over time; • To evaluate immunologic response and dysfunction (CD4+ and CD8+ absolute counts and percentage; CD4+/CD8+ ratio) in both arms; To test for emergent drug resistance-associated mutations (in integrase and reverse transcriptase) with standard genotypic assays (Sanger sequencing) in participants with protocol-defined virological failure (PDVF) in both arms; • To detect resistance-associated mutations (in integrase and reverse transcriptase) in participants with PDVF by means of a next generation sequencing assay detecting minority species at >1% prevalence • To evaluate the effects of the two strategies on fasting lipids (TC, LDL, HDL non-HDL, TC/ HDL) over time • To evaluate adherence levels to ARVs in both arms • To evaluate neuropsychiatric symptoms in both arms;Primary end point(s): Proportion of participants with virological rebound (viral load =50 copies/mL or premature discontinuations, irrespective of reason, with last viral load =50 copies/mL) at week 48. The novel primary end point | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Proportion of participants with HIV-1 RNA 1%), their resistance viral burden will be also evaluated. • Clinical and laboratory safety parameters; a descriptive analysis of all reported AEs and a quantitative analysis of AEs leading to treatment interruption/change will be used to evaluate long-term tolerability of the simplification treatment. • Changes in fasting lipids (TC, LDL, HDL, non-HDL, TC/HDL) from baseline to w48 and 96. • Absolute changes as well as proportion of participants above clinically relevant thresholds will be used to evaluate the change of metabolic parameters over time. • Changes of self-reported adherence level and proportion of participants with different adherence level (95%; 90%; 80%) from baseline to week 48 and 96. • Change in neuropsychiatric questionnaire scores, assessing mood, anxiety, sleep quality, and suicidality from baseline to week 24, 48 and 96.;Timepoint(s) of evaluation of this end point: 100 weeks | — |
Countries
Italy
Contacts
Public ContactAndrea Antinori
SIMIT – Società Italiana di Malattie Infettive e Tropicali
Outcome results
None listed