Protocol title: "Efficacy and safety of doravirine in the rapid initiation of highly active antiretroviral therapy (HAART) in HIV-1positive patients without prior treatment."
Protocol number: FH-96 Primary objective: To evaluate the antiviral activity of DOR/3TC/TDF at week 48 in HIV. Secondary objectives: 1\. To evaluate the antiviral activity of DOR/3TC/TDF at \< 200 coIPes/mL at week 48, using the intention-to-treat analysis (FDA snapshot analysis) for the exposed population (ITT-E). 2. To evaluate the antiviral activity of DOR/3TC/TDF at week 48 using an observed analysis (only including patients with available virological data). 3\. To evaluate the antiviral activity of DOR/3TC/TDF in the subgroup of participants with baseline ITINN mutations that do not confer resistance to doravirine, (according to the list of mutations defined in the exclusion criteria) by calculating the proportion of patients with viral load \<200 coIPes/mL and \<50 coIPes/mL at week 48. 4\. To evaluate the antiviral activity of DOR/3TC/TDF at \<200 coIPes/mL and \<50 coIPes/mL at week 24. 5\. To evaluate the safety and tolerability of DOR/3TC/TDF. 6. To evaluate the antiviral activity of DOR/3TC/TDF at week 48 in patients with a baseline viral load \>100,000 coIPes/mL. 7\. Immune response: to evaluate immune recovery (CD4, CD8 and CD4/CD8 T-cell counts at weeks 24 and 48. 8\. To evaluate the development of HIV-1 resistance in patients experiencing virological failure while undergoing treatment with DOR/3TC/TDF. 9\. To assess changes in weight, BMI, and liIPd profile (total cholesterol, HDL, LDL and triglycerides) at weeks 24 and 48. Study population: Subjects will be HIV-1 infection patient without ARV experience (naïve) within 30 days of diagnosis, willing to start ARV therapy in a rapid initiation setting, with ≥ 18 years of age, and who meet all inclusion criteria and do not meet any of the exclusion criteria. Study design: Phase IV, multicenter, non-randomized, single-arm, open-label study describing the antiviral efficacy, safety, and tolerability of DOR/3TC/TDF therapy as rapid initiation therapy in subjects with HIV-1 infection who have not received prior treatment. Regimens: Doravirine 100 mg; Lamivudine 300 mg; Tenofovir disoproxil 245 mg. Thirteen bottles. (Trade name: DELSTRIGO - MSD). Duration: 48 weeks. Sample size: 100 subjects
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
100
Pharmaceutical form: Oral tablets Unit dose concentration/dose level(s): 100/300/245 mg Administration instructions: Take one tablet once a day
Fundacion IDEAA -Infectologia de atencion ambulatoria
Ciudad Autonoma de Buenos Aire, Buenos Aires, Argentina
RECRUITINGFundacion Huesped
Buenos Aires, Argentina
RECRUITINGEvaluate the antiviral activity of DOR/3TC/TDF at week 48 in HIV patients without prior antiretroviral treatment, in a rapid initiation setting.
Proportion of patients with a viral load \< 50 copies/mL at week 48, as determined by an intention-to-treat analysis (FDA snapshot analysis) of the exposed population (ITT-E)
Time frame: 48 Weeks
Evaluate the antiviral activity of DOR/3TC/TDF at < 200 copies/mL at week 48, using the intention-to-treat analysis (FDA snapshot analysis) for the exposed population (ITT-E).
Proportion of patients with a viral load \< 200 copies/mL at week 48, using intention-to-treat analysis (FDA snapshot analysis) for the exposed population (ITT-E).
Time frame: 48 Weeks
Evaluate the antiviral activity of DOR/3TC/TDF at week 48 using an observed analysis (only including patients with available virological data).
Proportion of patients who achieved HIV-1 RNA levels \<50 copies/mL at week 48, in those with available data (observed analysis)
Time frame: 48 Weeks
Evaluate the antiviral activity of DOR/3TC/TDF in the subgroup of participants with baseline ITINN mutations that do not confer resistance to doravirine, by calculating the proportion of patients with viral load <200 c/mL and <50 c/mL at week 48.
Proportion of patients with viral load \< 200 copies/mL and viral load \< 50 copies/mL at week 48 in the subgroup of participants with baseline ITINN mutations that do not confer resistance to doravirine, according to the list of mutations defined in the exclusion criteria.
Time frame: 48 Weeks
Evaluate the antiviral activity of DOR/3TC/TDF at <200 copies/mL and <50 copies/mL at week 24.
Proportion of patients with viral load \< 200 copies/mL and viral load \< 50 copies/mL at week 24, using intention-to-treat analysis (FDA snapshot analysis) for the exposed population (ITT-E).
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Time frame: 24 Weeks
Evaluate the safety and tolerability of DOR/3TC/TDF.
Frequency, type, severity, and seriousness of adverse events and laboratory abnormalities, and proportion of patients who discontinued treatment with DOR/3TC/TDF due to adverse events or death
Time frame: 52 Weeks
Evaluate the antiviral activity of DOR/3TC/TDF at week 48 in patients with a baseline viral load >100,000 copies/mL.
Proportion of patients with a baseline HIV-1 RNA level \>100,000 c/mL who achieve virological suppression below 50 copies/mL at week 48 (ITT-E analysis).
Time frame: 48 Weeks
Immune response: evaluate immune recovery (CD4, CD8 and CD4/CD8 T-cell counts at weeks 24 and 48.
Changes in CD4 T-cell count, CD8 T-cell count, and CD4/CD8 ratio between baseline and weeks 24 and 48.
Time frame: 24 and 48 Weeks
Evaluate the development of HIV-1 resistance in patients experiencing virological failure while undergoing treatment with DOR/3TC/TDF
Number and type of resistance mutations in cases of virological failure.
Time frame: 48 Weeks
Assess changes in weight and BMI, at weeks 24 and 48.
Changes in weight and BMI between baseline and weeks 24 and 48. Weight and height will be combined to calculate BMI in kg/m\^2. Weight will be measured at all visits and height only at the baseline visit.
Time frame: 24 and 48 Weeks
Assess changes in lipid profile (total cholesterol, HDL, LDL and triglycerides) at weeks 24 and 48.
Changes in lipid profile (total cholesterol, HDL, LDL and triglycerides) between baseline and weeks 24 and 48.
Time frame: 24 and 48 Weeks