Lamivudine; Dolutegravir for HIV-1 infection

Inclusion criteria

• {"criterion_text":"- •\tHIV-1 documented infection\n- •\tAge 18 years\n- •\tTo be treated as ART naïve for overall less than 18 months before screening/baseline\n- •\tTo 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\n- •\tTo have reached a HIV-1 RNA <50 copies/mL during INSTI first-line therapy for less than 12 months. At least a single HIV-1 RNA determination below the threshold within the 6 months before enrollment is required (if a following determination in present, this should not be 50 copies (cp)/mL)\n- •\tEvidence of HbsAg negative less than 18 months before screening/baseline\n- •\tNo known allergy or intolerance to NRTIs, or INSTIs\n- •\tBeing able to comply with the protocol requirements\n- •\tInformed consent signed"}

Exclusion criteria

• {"criterion_text":"- •\tHaving failed virologically\n- •\tHaving changed the INSTI drug\n- •\tAny major INSTI- or NRTI-resistance-associated mutation documented before starting ART\n- •\tPregnancy or breast-feeding\n- •\tHBsAg positivity\n- •\tHCV-RNA positivity needing for any hepatitis C virus (HCV) therapy during the study\n- •\tAn active malignancy or opportunistic infection requiring active treatment\n- •\tWomen of childbearing potential not adopting an effective birth control system throughout the study period\n- •\tCreatinine clearance of <50 mL/min/1.73m2 via CKD-EPI method\n- •\tA life expectancy <2 years\n- •\tUse of HIV immunotherapeutic vaccines; other experimental agents, ART drugs not otherwise specified in the protocol, cytotoxic chemotherapy, systemically administered immunomodulators\n- •\tIndividuals who in the investigator’s judgment, poses a significant suicidality risk;\n- •\tMajor Depression, Bipolar Disorders and Psychoses"}

Primary endpoints

• {"endpoint_text":"- •\tProportion 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.","definition_or_measurement_approach":"Proportion of participants with virologic rebound at Week 48; primary analysis performed on the intention-to-treat (ITT) population using the US FDA snapshot algorithm (non-inferiority margin 4%)."}

Secondary endpoints

• {"endpoint_text":"- Proportion of participants with HIV-1 RNA <50 copies/mL at week 48 (FDA Snapshot algorithm)","definition_or_measurement_approach":"Measured as proportion with HIV-1 RNA <50 copies/mL at Week 48 using the FDA Snapshot algorithm."}
• {"endpoint_text":"- Time to virological rebound (defined as the first of two consecutive HIV-1 RNA >=50 copies/mL)","definition_or_measurement_approach":"Time-to-event measured as time to first of two consecutive HIV-1 RNA ≥50 copies/mL."}
• {"endpoint_text":"- Changes in CD4+ and CD8+ T-lymphocyte counts (absolute and percentage), and in CD4+/CD8+ ratio (as a measure of immune activation) in the peripheral blood from baseline to week 48 and 96.","definition_or_measurement_approach":"Measured by absolute and percentage counts of CD4+ and CD8+ and CD4+/CD8+ ratio at baseline, Week 48 and Week 96."}
• {"endpoint_text":"- Proportion of participants developing resistance-conferring mutations (to any drug class) by genotypic resistance test (GRT) in plasma or proviral DNA (in case of low viremia levels, <200 copies/mL) at protocol-defined virological failure (PDVF) will be cumulatively described throughout the study period.","definition_or_measurement_approach":"Genotypic resistance testing on plasma or proviral DNA at PDVF; cumulative description throughout study."}
• {"endpoint_text":"- Viral minority variants harboring resistance associated mutations (to any drug class) at the time of PDVF will be characterized in plasma or in proviral DNA (in case of low viremia levels, <200 copies/mL) by next generation sequencing. For the minority resistant variants detected (prevalence >1%), their resistance viral burden will be also evaluated","definition_or_measurement_approach":"Next generation sequencing (NGS) on plasma or proviral DNA at PDVF; minority variants >1% prevalence characterized and resistance viral burden evaluated."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Descriptive analysis of reported adverse events and quantitative analysis of AEs leading to treatment interruption/change; clinical and laboratory safety monitoring."}
• {"endpoint_text":"- Changes in fasting lipids (TC, LDL, HDL, non-HDL, TC/HDL) from baseline to w48 and 96. •\tAbsolute changes as well as proportion of participants above clinically relevant thresholds will be used to evaluate the change of metabolic parameters over time. •\tChanges of self-reported adherence level and proportion of participants with different adherence level (95%; 90%; 80%) from baseline to week 48 and 96.","definition_or_measurement_approach":"Fasting lipid panel measured at baseline, Week 48 and Week 96; absolute changes and proportion above thresholds; self-reported adherence levels evaluated (95%, 90%, 80%)."}
• {"endpoint_text":"- Change in neuropsychiatric questionnaire scores, assessing mood, anxiety, sleep quality, and suicidality from baseline to week 24, 48 and 96.","definition_or_measurement_approach":"Standardized neuropsychiatric questionnaires administered at baseline, Weeks 24, 48 and 96 to assess mood, anxiety, sleep quality and suicidality."}
• {"endpoint_text":"- Virological Sub-study Changes in residual viremia (limit of detection: 3 copies/mL) from baseline to week 24 and 48. Percentage of participants with residual viremia at week 24 and 48. Impact of residual viremia at baseline on virological response. •\tChange in total HIV-1 DNA in PBMCs from baseline to week 24 and 48. •\tImpact of total DNA at baseline on virological response. •\tChange in level of cell-associated HIV-1 RNA in PBMCs from baseline to week 24 and 48.","definition_or_measurement_approach":"Virological sub-study measurements: residual viremia (LOD 3 copies/mL), total HIV-1 DNA and cell-associated HIV-1 RNA in PBMCs at baseline, Week 24 and Week 48; analyses of impact on response."}
• {"endpoint_text":"- •Impact of total DNA at baseline on virological response.•Change in level of cell-associated HIV-1 RNA in PBMCs from baseline to week 24 and 48. •Impact of cell-associated HIV-1 RNA in PBMCs at baseline on virological response. Correlations between cell-associated HIV-1 RNA in PBMCs,total HIV DNA,and RNA levels.Characterization of minority RT integrase resistance mutations(at >1% prevalence)and their relative abundance in PBMCs at baseline, and their impact on virological failure at 24 and 48wk","definition_or_measurement_approach":"Analyses of total HIV DNA and cell-associated RNA in PBMCs and correlations with plasma RNA; NGS characterization of minority resistance mutations (>1%) in PBMCs and impact on failure at Weeks 24 and 48."}
• {"endpoint_text":"- Immunological Sub-study •Impact of regimen switching on the percentage of activated(%CD38+DR+),senescent(CD28-CD57+)T-cell lymphocytes and on T helper profile(Th1, Th2,TH9, Th17, Th21);Impact of regimen switching on different B cell (naïve, memory and activated),NK and monocytes subsets and on regulatory cells (Treg and MDSC);. •Impact of regimen switching on the Principal Component analysis of immunological markers •\tImpact of regimen switching on inflammation and pro-coagulation markers","definition_or_measurement_approach":"Immunological sub-study measuring activation and senescence markers, B/NK/monocyte subsets, regulatory cells, PCA of immunological markers, and inflammation/pro-coagulation markers at planned timepoints."}
• {"endpoint_text":"- Renal bone and weight Sub-study Changes in urinary tubular damage markers [alpha1-microglobulin, beta2-microglobulin, retinal binding protein (RBP) and albumin-creatinine ratio (ACR)], from baseline to week 24 and 48. •\tBMD change by DXA scan. •\tEnrolled patients may also undergo only part of the evaluations planned for the substudy","definition_or_measurement_approach":"Measurements of urinary tubular damage markers and BMD by DXA at baseline, Week 24 and Week 48; sub-study participants may undergo partial evaluations."}
• {"endpoint_text":"- Neurologic Sub-study •\tChange in neurocognitive performance assessed by a standardized neuropsychological battery (NPZ-14) from baseline to week 48 and 96. •\tChange in plasma NFL concentration from baseline to week 48 and 96","definition_or_measurement_approach":"Neurocognitive NPZ-14 battery and plasma NFL concentration measured at baseline, Weeks 48 and 96."}
• {"endpoint_text":"- PROs and QoL Sub-study Change in QoL and PROs items from baseline to week 48 and 96 by standardized validate self-reported questionnaires.","definition_or_measurement_approach":"Patient-reported outcomes and QoL assessed with validated self-reported questionnaires at baseline, Week 48 and Week 96."}

Italy

Earliest CTIS Part Ii Submission Date

10-10-2024

Latest Decision Or Authorization Date

08-05-2026

Processing Time Days

575

Number Of Sites

29

Number Of Participants

440

Primary sponsor

Full Name

Societa Italiana Di Malattie Infettive E Tropicali SIMIT

Organisation Type

Laboratory/Research/Testing facility

Country Of Registered Address

Italy