Protocol Title: DOLCE: Dolutegravir-Lamivudine for naïve HIV-Infected Patients with ≤200 CD4/mm3 Protocol Number: FH-57 Study Objectives: To assess the antiviral activity at week 48 of DTG+3TC among naïve HIV patients with a CD4 count ≤200 cells /mm3.
Primary endpoint: Proportion of patients with viral load \< 50 copies/mL at week 48 using the ITT-exposed analysis (FDA snapshot) for the intent-to-treat exposed (ITT-E) population. Secondary Objectives: * To assess the antiviral activity of DTG+3TC and DTG+TDF/XTC at week 24 * To evaluate the safety and tolerability of DTG+3TC and DTG+TDF/XTC over time * To assess the antiviral activity of DTG+3TC and DTG+TDF/XTC at week 48 in patients with baseline viral load \>100,000 c/mL * To evaluate immunological activity (CD4+ lymphocyte \[CD4 counts\]) at Week 24 and Week 48 * To assess the development of HIV-1 resistance in patients with virologic failure or viral rebound treated with DTG+3TC or DTG+TDF/XTC * To evaluate the incidence of disease progression (HIV-associated conditions, AIDS and death) of DTG + 3TC and DTG + TDF/XTC over time. Secondary endpoints: * Proportion of patients treated with DTG+3TC and DTG+TDF/XTC with HIV-1 levels of less than 50 copies/mL at week 24 * Frequency, type and severity of adverse events and laboratory abnormalities and proportion of patients who discontinue DTG+3TC or DTG+TDF/XTC due to adverse events or death * Proportion of patients with baseline HIV-1 RNA \>100,000 c/mL that achieve virological suppression at week 48 weeks, * Changes in CD4 count, CD8 count and CD4/CD8 ratio between baseline and 48 weeks * Number and type of resistance mutations in case of virologic failure (defined as a confirmed viral above 200 copies/mL after week 24 copies/mL or viral rebound at any timepoint) * Incidence of IRIS and disease progression (HIV associated conditions, AIDS and death). Tertiary objectives: ● TDF/XTCTo explore change in health-related quality-of-life for subjects treated with DTG plus 3TC and DTG + TDF/XTC Tertiary endpoints: ● Change from Baseline in health-related quality of life using EQ-5D-5L and PHQ9 at Weeks 24, and 48 Patient Population: HIV-1-infected subjects aged \>18 years who are naïve to antiretroviral therapy with ≤200 CD4 cell/mm3 Study Design: Prospective, Phase IV, randomized, multicenter, parallel group study design Regimens: Dolutegravir 50 mg /lamivudine 300 mg QD FDC. Dolutegravir 50 mg QD plus tenofovir 300 mg/emtricitabine 200mg or plus tenofovir 300 mg/ lamivudine 300 mg. Duration: 48 weeks Sample size:230 subjects
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
265
1 pill QD
Fundación Huésped
Ciudad Autonoma de Buenos Aire, Buenos Aires, Argentina
Hospital General de Agudos Dr. Cosme Argerich
Ciudad Autonoma de Buenos Aire, Buenos Aires, Argentina
Hospital de Infecciosas Francisco Javier Muñiz
Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina
Antiviral Activity at Week 48 of DTG+3TC Among ART-naïve HIV Patients With a CD4 Count ≤200 Cells/mm3.
Percentage of patients with viral load \< 50 copies/mL at week 48 using the ITT-exposed analysis (FDA snapshot) for the intent-to-treat exposed (ITT-E) population.
Time frame: Week 48
Antiviral Activity of DTG+3TC and DTG+TDF/XTC (TDF/FTC or TDF/3TC) at Week 24
Percentage of patients treated with DTG+3TC and DTG+TDF/XTC with HIV-1 levels of less than 50 copies/mL at week 24
Time frame: Week 24
Safety and Tolerability of DTG+3TC and DTG+TDF/XTC Over Time
Percentage of patients who discontinue treatment due to adverse events or death
Time frame: week 48
Antiviral Activity of DTG+3TC and DTG+TDF/XTC at Week 48 in Patients With Baseline Viral Load >100,000 c/mL
Percentage of patients with baseline viral load \>100,000 c/mL that reach HIV-1 levels of less than 50 copies/mL at week 48
Time frame: Week 48
Changes in Lymphocytes Subsets Between Baseline and 48 Weeks
Changes in lymphocytes CD4 cells count per mL
Time frame: Week 48
Development of HIV-1 Resistance in Patients With Virologic Failure or Viral Rebound Whilst Being Treated With DTG+3TC or DTG+TDF/XTC
Number and type of resistance mutations in case of virologic failure (defined as a confirmed viral above 200 copies/mL on or after week 24 or confirmed viral rebound at any timepoint)
Time frame: week 48
Incidence of IRIS or Disease Progression (HIV Associated Conditions, AIDS and Death).
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Instituto CAICI
Rosario, Santa Fe Province, Argentina
Hospital de Agudos J.A.Fernandez
Buenos Aires, Argentina
Fundação Bahiana de Infectologia
Salvador, Estado de Bahia, Brazil
HUOC - Hospital Universitário Oswal do Cruz - Universidade de Pernambuco
Recife, Pernambuco, Brazil
Hospital Geral de Nova Iguaçu
Nova Iguaçu, Rio de Janeiro, Brazil
Hospital de Clínicas de Porto Alegre
Porto Alegre, Rio Grande do Sul, Brazil
Centro de Pesquisa: Instituto de Infectologia Emílio Ribas
Pacaembu, São Paulo, Brazil
...and 1 more locations
Evaluation of disease progression incidence (HIV-associated conditions, AIDS and death) with DTG+3TC and DTG + TDF/XTC treatment over time
Time frame: week 48