Efficacy and Safety of Doravirine in the Rapid Initiation

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.