Evaluating the Pharmacokinetics, Safety, and Tolerability of Doravirine (MK-1439) and Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (MK-1439A) in HIV-1-Infected Children and Adolescents

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT03332095
• Collaborator: (none)
• Enrollment: 55
• Locations: 8
• Arms: 2
• Actual Duration (Months): 46.8
• Patients Per Site: 6.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study was to evaluate the pharmacokinetics, safety, and tolerability of doravirine (also called MK-1439 or DOR) and doravirine/lamivudine/tenofovir disoproxil fumarate (also called MK-1439A or DOR/3TC/TDF) in HIV-1-infected children and adolescents.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections	Drug: Doravirine (DOR); Drug: Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (DOR/3TC/TDF); Drug: Antiretroviral (ARV) medications	Phase 1/Phase 2

Detailed Description

This study evaluated the pharmacokinetics (PK), safety, and tolerability of DOR and DOR/3TC/TDF in HIV-1-infected children and adolescents.

This study was conducted in two cohorts: Cohort 1 and Cohort 2. At study entry (Day 0), participants in Cohort 1 received a single dose of DOR added to their current HIV regimens. (The antiretroviral drugs in their current HIV regimens were not be provided by the study.) Participants in Cohort 1 underwent intensive PK evaluations, and had an additional study visit at Week 2.

The study team in consultation with a Study Monitoring Committee evaluated data from Cohort 1 before enrolling participants in Cohort 2. Participants in Cohort 2 received DOR/3TC/TDF once daily from Day 0 through Week 96. They had study visits at Weeks 1, 2, 4, 8, 12, 16, 24, 36, 48, 64, 80, and 96. Study visits included physical examinations, PK evaluations, and blood and urine collection.

Study Design

• Study Type: Interventional
• Actual Enrollment: 55 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I/II Study of the Pharmacokinetics, Safety and Tolerability of Doravirine (MK-1439) and Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (MK-1439A) in HIV-1-Infected Children and Adolescents
• Actual Study Start Date: Jul 2, 2018
• Actual Primary Completion Date: Aug 19, 2020
• Actual Study Completion Date: May 25, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1: DOR Participants received a single dose of DOR at study entry (Day 0).	Drug: Doravirine (DOR); 100 mg of DOR administered orally; Other Names: MK-1439 ; Drug: Antiretroviral (ARV) medications; Participants in Cohort 1 received a combination of dolutegravir (DTG) or raltegravir (RAL) plus two nucleoside reverse transcriptase inhibitors (NRTIs). The ARV drugs were prescribed by participants' own health care providers and were not provided by the study.; Other Names: ARVs
Experimental: Cohort 2: DOR/3TC/TDF Participants received DOR/3TC/TDF from Day 0 through Week 96.	Drug: Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (DOR/3TC/TDF); DOR/3TC/TDF administered orally as a fixed-dose combination (as a tablet, 100 mg/300 mg/300 mg) once daily; Other Names: MK-1439A

Outcome Measures

Primary Outcome Measures

1. Pharmacokinetic (PK) Parameter: Single-dose Area-under-the-curve (AUC0-∞) of Doravirine (DOR) (Cohort 1) [Measured during the entry (day 0) visit. Blood samples were drawn at pre-dose, and at 1, 2, 4, 8, 12, 24, 48 and 72 hours post-dose.]

   Pharmacokinetic parameters were determined from plasma concentration-time profiles using non-compartmental methods (WinNonlin version 6.3, Pharsight Corp., Mountain View, CA). Area under the curve (AUC) was determined using non-compartmental analyses and estimated by the linear up/log down trapezoidal rule, from time zero to infinity. Steady state AUC0-24 is equivalent to single dose AUC0-∞.

2. PK Parameter: Single-dose Maximum Concentration (Cmax) of DOR (Cohort 1) [Measured during the entry (day 0) visit. Blood samples were drawn at pre-dose, and at 1, 2, 4, 8, 12, 24, 48 and 72 hours post-dose.]

   Pharmacokinetic parameters were determined from plasma concentration-time profiles using non-compartmental methods (WinNonlin, version 6.3, Pharsight Corp., Mountain View, CA).

3. PK Parameter: Single-dose 24 Hour-concentration (C24hr) of DOR (Cohort 1) [Measured during the entry (day 0) visit. Blood samples were drawn at pre-dose, and at 1, 2, 4, 8, 12, 24, 48 and 72 hours post-dose.]

   Pharmacokinetic parameters were determined from plasma concentration-time profiles using non-compartmental methods (WinNonlin, version 6.3, Pharsight Corp., Mountain View, CA).

4. Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) Assessed as Related to Study Drug [Cohort 1: Measured from Day 0 through Week 2; Cohort 2: Measured from Day 0 through Week 24.]

   Percentage and Clopper-Pearson 95% Confidence Interval (CI) of participants with Grade 3 or higher AEs judged by the medical clinic as related to the study drug. AEs were graded based on the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017 (see References).

5. Percentage of Participants With Serious Adverse Events (SAEs) Assessed as Related to Study Drug [Cohort 1: Measured from Day 0 through Week 2; Cohort 2: Measured from Day 0 through Week 24.]

   Percentage and Clopper-Pearson 95% CI of participants with SAEs judged by the medical clinic as related to the study drug. SAEs were reported according to Version 2.0 of the Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE Manual) (see references).

6. Percentage of Participants With Permanent Discontinuation of Study Drug Due to Adverse Events Assessed as Related to Study Drug [Cohort 1: Measured from Day 0 through Week 2; Cohort 2: Measured from Day 0 through Week 24.]

   Percentage and Clopper-Pearson 95% CI of participants with permanent discontinuation of study drug due to AEs judged by the medical clinic as related to the study drug.

7. Percentage of Participants With Grade 5 Adverse Events (Death) Regardless of Relationship to Study Drug [Cohort 1: Measured from Day 0 through Week 2; Cohort 2: Measured from Day 0 through Week 24.]

   Percentage and Clopper-Pearson 95% CI of participants with Grade 5 AEs (death) regardless of relationship to study drug.

Secondary Outcome Measures

1. PK Parameter: AUC0-24hr of DOR (Cohort 2) [Measured at Week 1 visit. Blood samples were drawn at pre-dose, and at 2, 4, 12 and 24 hours post-dose.]

   Pharmacokinetic parameters were determined from plasma concentration-time profiles using non-compartmental methods (WinNonlin, version 6.3, Pharsight Corp., Mountain View, CA). Area under the curve (AUC) was determined using non-compartmental analyses and estimated by the linear up/log down trapezoidal rule, from time zero to 24 hours. Intensive PK samples were collected for the first ten participants enrolled in Cohort 2.

2. PK Parameter: AUC0-24hr of 3TC (Cohort 2) [Measured at Week 1 visit. Blood samples were drawn at pre-dose, and at 1, 2, 4, 8, 12 and 24 hours post-dose.]

   Pharmacokinetic parameters were determined from plasma concentration-time profiles using non-compartmental methods (WinNonlin, version 6.3, Pharsight Corp., Mountain View, CA). Area under the curve (AUC) was determined using non-compartmental analyses and estimated by the linear up/log down trapezoidal rule, from time zero to 24 hours. Intensive PK samples were collected for the first ten participants enrolled in Cohort 2.

3. PK Parameter: AUC0-24hr of Tenofovir (Cohort 2) [Measured at Week 1 visit. Blood samples were drawn at pre-dose, and at 1, 2, 4, 8, 12 and 24 hours post-dose.]

   Pharmacokinetic parameters were determined from plasma concentration-time profiles using non-compartmental methods (WinNonlin, version 6.3, Pharsight Corp., Mountain View, CA). Area under the curve (AUC) was determined using non-compartmental analyses and estimated by the linear up/log down trapezoidal rule, from time zero to 24 hours. Intensive PK samples were collected for the first ten participants enrolled in Cohort 2.

4. PK Parameter: Cmax of DOR (Cohort 2) [Measured at Week 1 visit. Blood samples were drawn at pre-dose, and at 2, 4, 12 and 24 hours post-dose.]

   Pharmacokinetic parameters were determined from plasma concentration-time profiles using non-compartmental methods (WinNonlin, version 6.3, Pharsight Corp., Mountain View, CA). Cmax was projected from individual plasma concentration-time profiles using the non-parametric superposition function in WinNonLin v6.3. Intensive PK samples were collected for the first ten participants enrolled in Cohort 2.

5. PK Parameter: Cmax of 3TC (Cohort 2) [Measured at Week 1 visit. Blood samples were drawn at pre-dose, and at 1, 2, 4, 8, 12 and 24 hours post-dose.]

   Pharmacokinetic parameters were determined from plasma concentration-time profiles using non-compartmental methods (WinNonlin, version 6.3, Pharsight Corp., Mountain View, CA). Cmax was projected from individual plasma concentration-time profiles using the non-parametric superposition function in WinNonLin v6.3. Intensive PK samples were collected for the first ten participants enrolled in Cohort 2.

6. PK Parameter: Cmax of Tenofovir (Cohort 2) [Measured at Week 1 visit. Blood samples were drawn at pre-dose, and at 1, 2, 4, 8, 12 and 24 hours post-dose.]

   Pharmacokinetic parameters were determined from plasma concentration-time profiles using non-compartmental methods (WinNonlin, version 6.3, Pharsight Corp., Mountain View, CA). Cmax was projected from individual plasma concentration-time profiles using the non-parametric superposition function in WinNonLin v6.3. Intensive PK samples were collected for the first ten participants enrolled in Cohort 2.

7. PK Parameter: C24hr of DOR (Cohort 2) [Measured at Week 1 visit. Blood samples were drawn at pre-dose, and at 2, 4, 12 and 24 hours post-dose.]

   Pharmacokinetic parameters were determined from plasma concentration-time profiles using non-compartmental methods (WinNonlin, version 6.3, Pharsight Corp., Mountain View, CA). C24hr was projected from individual plasma concentration-time profiles using the non-parametric superposition function in WinNonLin v6.3. Intensive PK samples were collected for the first ten participants enrolled in Cohort 2.

8. PK Parameter: C24hr of 3TC (Cohort 2) [Measured at Week 1 visit. Blood samples were drawn at pre-dose, and at 1, 2, 4, 8, 12 and 24 hours post-dose.]

   Pharmacokinetic parameters were determined from plasma concentration-time profiles using non-compartmental methods (WinNonlin, version 6.3, Pharsight Corp., Mountain View, CA). C24hr was projected from individual plasma concentration-time profiles using the non-parametric superposition function in WinNonLin v6.3. Intensive PK samples were collected for the first ten participants enrolled in Cohort 2.

9. PK Parameter: C24hr of Tenofovir (Cohort 2) [Measured at Week 1 visit. Blood samples were drawn at pre-dose, and at 1, 2, 4, 8, 12 and 24 hours post-dose.]

   Pharmacokinetic parameters were determined from plasma concentration-time profiles using non-compartmental methods (WinNonlin, version 6.3, Pharsight Corp., Mountain View, CA). C24hr was projected from individual plasma concentration-time profiles using the non-parametric superposition function in WinNonLin v6.3. Intensive PK samples were collected for the first ten participants enrolled in Cohort 2.

10. Percentage of Participants With Plasma HIV-1 RNA Less Than 200 Copies/mL at Week 24 (Cohort 2) [Measured at week 24.]

    Virologic responses were assessed at week 24 as percentage (%) of participants and Clopper-Pearson 95% CI. Missing values were considered as failures for participants with missing data due to discontinuation of study drug as a result of virologic failure or for non-treatment related reasons with last available RNA >200 copies/mL; otherwise participants with missing values were excluded.

11. Percentage of Participants With Plasma HIV-1 RNA Less Than 200 Copies/mL at Week 48 (Cohort 2) [Measured at week 48.]

    Virologic responses were assessed at week 48 as percentage (%) of participants and Clopper-Pearson 95% CI. Missing values were considered as failures for participants with missing data due to discontinuation of study drug as a result of virologic failure or for non-treatment related reasons with last available RNA >200 copies/mL; otherwise participants with missing values were excluded. The study is ongoing and the participants are still in follow up (post PCD). Results will be added at the end of the study follow-up.

12. Percentage of Participants With Plasma HIV-1 RNA Less Than 200 Copies/mL at Week 96 (Cohort 2) [Measured at week 96.]

    Virologic responses were assessed at week 96 as percentage (%) of participants and Clopper-Pearson 95% CI. Missing values were considered as failures for participants with missing data due to discontinuation of study drug as a result of virologic failure or for non-treatment related reasons with last available RNA >200 copies/mL; otherwise participants with missing values were excluded. The study is ongoing and the participants are still in follow up (post PCD). Results will be added at the end of the study follow-up.

13. Percentage of Participants With Plasma HIV-1 RNA Less Than 50 Copies/mL at Week 24 (Cohort 2) [Measured at week 24.]

    Virologic responses were assessed at week 24 as percentage of participants and Clopper-Pearson 95% CI. Missing values were considered as failures for participants with missing data due to discontinuation of study drug as a result of virologic failure or for non-treatment related reasons with last available RNA >50 copies/mL. Otherwise participants with missing values were excluded.

14. Percentage of Participants With Plasma HIV-1 RNA Less Than 50 Copies/mL at Week 48 (Cohort 2) [Measured at week 48.]

    Virologic responses were assessed at week 48 as percentage of participants and Clopper-Pearson 95% CI. Missing values were considered as failures for participants with missing data due to discontinuation of study drug as a result of virologic failure or for non-treatment related reasons with last available RNA >50 copies/mL. Otherwise participants with missing values were excluded. The study is ongoing and the participants are still in follow up (post PCD). Results will be added at the end of the study follow-up.

15. Percentage of Participants With Plasma HIV-1 RNA Less Than 50 Copies/mL at Week 96 (Cohort 2) [Measured at week 96.]

    Virologic responses were assessed at week 96 as percentage of participants and Clopper-Pearson 95% CI. Missing values were considered as failures for participants with missing data due to discontinuation of study drug as a result of virologic failure or for non-treatment related reasons with last available RNA >50 copies/mL. Otherwise participants with missing values were excluded. The study is ongoing and the participants are still in follow up (post PCD). Results will be added at the end of the study follow-up.

16. Percentage of Participants With Plasma HIV-1 RNA Less Than 40 Copies/mL at Week 24 (Cohort 2) [Measured at week 24.]

    Virologic responses were assessed at week 24 as percentage (%) of participants and Clopper-Pearson 95% CI. Missing values were considered as failures for participants with missing data due to discontinuation of study drug as a result of virologic failure or for non-treatment related reasons with last available RNA >40 copies/mL; Otherwise participants with missing values were excluded.

17. Percentage of Participants With Plasma HIV-1 RNA Less Than 40 Copies/mL at Week 48 (Cohort 2) [Measured at week 48.]

    Virologic responses were assessed at week 48 as percentage (%) of participants and Clopper-Pearson 95% CI. Missing values were considered as failures for participants with missing data due to discontinuation of study drug as a result of virologic failure or for non-treatment related reasons with last available RNA >40 copies/mL; Otherwise participants with missing values were excluded. The study is ongoing and the participants are still in follow up (post PCD). Results will be added at the end of the study follow-up.

18. Percentage of Participants With Plasma HIV-1 RNA Less Than 40 Copies/mL at Week 96 (Cohort 2) [Measured at week 96.]

    Virologic responses were assessed at week 96 as percentage (%) of participants and Clopper-Pearson 95% CI. Missing values were considered as failures for participants with missing data due to discontinuation of study drug as a result of virologic failure or for non-treatment related reasons with last available RNA >40 copies/mL; Otherwise participants with missing values were excluded. The study is ongoing and the participants are still in follow up (post PCD). Results will be added at the end of the study follow-up.

19. Summary of log10 Drop From Baseline to Week 24 in Plasma HIV-1 RNA (ART-naive Participants) (Cohort 2) [Measured at Day 0 and week 24.]

    The differences between log10 HIV RNA at Week 24 minus at the Day 0 are summarized.

20. Summary of log10 Drop From Baseline to Week 48 in Plasma HIV-1 RNA (ART-naive Participants) (Cohort 2) [Measured at Day 0 and week 48.]

    The differences between log10 HIV RNA at Week 48 minus at the Day 0 are summarized. The study is ongoing and the participants are still in follow up (post PCD). Results will be added at the end of the study follow-up.

21. Summary of log10 Drop From Baseline to Week 96 in Plasma HIV-1 RNA (ART-naive Participants) (Cohort 2) [Measured at Day 0 and week 96.]

    The differences between log10 HIV RNA at Week 96 minus at the Day 0 are summarized. The study is ongoing and the participants are still in follow up (post PCD). Results will be added at the end of the study follow-up.

22. Summary of Changes in CD4 Count From Baseline to Week 24 (Cohort 2) [Measured at Day 0 and week 24.]

    The mean differences between CD4 count at Week 24 minus at the Day 0, and 95% Clopper-Pearson CI, are presented.

23. Summary of Changes in CD4 Count From Baseline to Week 48 (Cohort 2) [Measured at Day 0 and week 48.]

    The mean differences between CD4 count at Week 48 minus at the Day 0, and 95% Clopper-Pearson CI, are presented. The study is ongoing and the participants are still in follow up (post PCD). Results will be added at the end of the study follow-up.

24. Summary of Changes in CD4 Count From Baseline to Week 96 (Cohort 2) [Measured at Day 0 and week 96.]

    The mean differences between CD4 count at Week 96 minus at the Day 0, and 95% Clopper-Pearson CI, are presented. The study is ongoing and the participants are still in follow up (post PCD). Results will be added at the end of the study follow-up.

25. Summary of Changes in CD4 Percent From Baseline to Week 24 (Cohort 2) [Measured at Day 0 and week 24.]

    The mean differences between CD4 percent at Week 24 minus at the Day 0, and 95% Clopper-Pearson CI, are presented.

26. Summary of Changes in CD4 Percent From Baseline to Week 48 (Cohort 2) [Measured at Day 0 and week 48.]

    The mean differences between CD4 percent at Week 48 minus at the Day 0, and 95% Clopper-Pearson CI, are presented. The study is ongoing and the participants are still in follow up (post PCD). Results will be added at the end of the study follow-up.

27. Summary of Changes in CD4 Percent From Baseline to Week 96 (Cohort 2) [Measured at Day 0 and week 96.]

    The mean differences between CD4 percent at Week 96 minus at the Day 0, and 95% Clopper-Pearson CI, are presented. The study is ongoing and the participants are still in follow up (post PCD). Results will be added at the end of the study follow-up.

28. Percentage of Participants With Grade 3 or Higher Adverse Events Assessed as Related to Study Drug (Cohort 2) Through End of Study [Measured from Day 0 through Week 96.]

    Percentage and Clopper-Pearson 95% CI of participants with Grade 3 or higher AEs judged by the medical clinic as related to the study drug. AEs were graded based on the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017 (DAIDS) AE Grading table corrected version 2.1 (see References). These results will be added at the end of the study.

29. Percentage of Participants With Serious Adverse Events Assessed as Related to Study Drug (Cohort 2) Through End of Study [Measured from Day 0 through Week 96.]

    Percentage and Clopper-Pearson 95% CI of participants with SAEs judged by the medical clinic as related to the study drug. SAEs were reported according to version 2.0 of the Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE Manual) (see references). These results will be added at the end of the study.

30. Percentage of Participants With Permanent Discontinuation of Study Drug Due to Adverse Events Assessed as Related to Study Drug (Cohort 2) Through End of Study [Measured from Day 0 through Week 96.]

    Percentage and Clopper-Pearson 95% CI of participants with permanent discontinuation of study drug due to AEs judged by the medical clinic as related to the study drug. These results will be added at the end of the study.

31. Percentage of Participants With Grade 5 Adverse Events (Death) Regardless of Relationship to Study Drug (Cohort 2) Through End of Study [Measured from Day 0 through Week 96.]

    Percentage and Clopper-Pearson 95% CI of participants with Grade 5 adverse events (death). These results will be added at the end of the study.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Weight greater than or equal 35 kg at entry

• If not of legal age to provide independent informed consent: Parent or guardian was willing and able to provide written informed consent for study participation; in addition, when applicable per local Institutional Review Board / Ethics Committee (IRB/EC) policies and procedures, potential participant was willing and able to provide written informed assent for study participation. If of legal age to provide independent informed consent as determined by site Standard Operating Procedures (SOPs) and consistent with site IRB/EC policies and procedures: Potential participant was willing and able to provide written informed consent for study participation

• Confirmed HIV-1-infection based on documented testing of two samples collected at different time points. More information on this criterion can be found in the protocol.

• Antiretroviral therapy (ART) exposure, virologic suppression, and resistance requirements, as follows:

Cohort 1

• ART exposure requirements, based on individual or parent/guardian's report and, if available, confirmed by medical records:

• At entry, receiving combination ART with raltegravir (RAL) or dolutegravir (DTG) plus 2 nucleoside reverse transcriptase inhibitors (NRTIs); AND

• At entry, had not received non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitor (PIs), or cobicistat within the previous 30 days; AND

• Virologic suppression, as documented in medical records and as defined by:

• One or more HIV RNA polymerase chain reaction (PCR) result below the level of quantification (BLLQ) within 15 months prior to enrollment, AND

• If any HIV RNA PCR tests had been done within 3 months prior to enrollment, all results were below the level of quantification, AND

• HIV RNA PCR result less than 40 copies/mL at screening, performed as per the protocol.

Cohort 2 ART-naive

• ART exposure requirements, based on individual or parent/guardian's report and, if available, confirmed by medical records:

• At entry, received no antiretrovirals (ARVs) for treatment of HIV infection including investigational agents (prior receipt of ARVs for prevention of perinatal transmission was permitted); AND

• Screening genotypic resistance test results indicated susceptibility to doravirine (DOR), tenofovir disoproxil fumarate (TDF), and lamivudine (3TC) (see the protocol for more information; result must be available prior to enrollment), performed as per the protocol; AND

• If available, as documented in medical records, any prior genotypic resistance test result indicated susceptibility to DOR, TDF, and 3TC (see the protocol for more information).

Note: For individuals that were re-screened, the genotypic resistance test did not need to be repeated.

Cohort 2 ART-experienced

• ART exposure requirements, based on individual or parent/guardian's report and, if available, confirmed by medical records:

• No previous history of change in ARVs due to clinical or virologic failure, in the opinion of the site investigator or designee; AND

• Virologic suppression, as documented in medical record and as defined by:

• One or more HIV RNA PCR result BLLQ within 15 months prior to enrollment, AND

• If any HIV RNA PCR tests had been done within 3 months prior to enrollment, all results were below the level of quantification, AND

• HIV RNA PCR result less than 40 copies/mL at screening (see the protocol for more information); AND

• If available, as documented in medical records, any prior genotypic resistance test result indicated susceptibility to DOR, TDF, and 3TC (see the protocol for more information).

Note: This group of ARV-experienced, virologically suppressed participants were only enrolled once there was data from the adult switch studies indicating virologic efficacy and safety (see the protocol for more information). Sites were informed via a Clarification Memorandum when ART-experienced participants can be enrolled. A single, unconfirmed HIV-1 RNA result greater than or equal to the level of quantification but less than 500 copies/mL, between 3 and 15 months, prior to enrollment was not exclusionary as long as the other criteria for documentation of virologic suppression were met.

• Grade 2 or lower hemoglobin, aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase, and lipase on specimens obtained at screening

• For Cohort 2 only, grade 2 or lower creatinine, proteinuria, and glycosuria on specimens obtained at screening

• Estimated glomerular filtration rate (eGFR) greater than or equal to 60 mL/min/1.73 m^2, on specimens obtained at screening, based on the Schwartz equation. More information on this criterion can be found in the protocol.

• For females who had reached menarche or who were engaging in sexual activity (self-reported), negative pregnancy test at entry

• For females engaging in sexual activity that could lead to pregnancy (self-reported), agreed to use two effective, medically accepted birth control methods while on study and for two weeks after permanently discontinuing study drug

• For males engaging in sexual activity that could lead to pregnancy (self-reported), agreed to use condoms while on study and for two weeks after permanently discontinuing study drug

• Able and willing to swallow available formulation(s) (tablet or, as available, oral granules).

Exclusion Criteria:

• Evidence of decompensated liver disease manifested by the presence of or a history of ascites, esophageal or gastric variceal bleeding, hepatic encephalopathy, or other signs or symptoms of advanced liver diseases.

Note: Individuals with chronic hepatitis B who had grade 2 or lower ALT and AST and had no significant impairment of hepatic synthetic function (significant impairment of hepatic synthetic function was defined as a serum albumin less than 2.8 mg/dL or an international normalized ratio (INR) greater than 1.7 in the absence of another explanation for the abnormal laboratory value) were eligible.

• For Cohort 2 only, detectable hepatitis C virus (HCV) by RNA PCR or current or planned treatment with direct antiviral agent for HCV.

Note: HCV antibody positivity but undetectable by HCV RNA PCR results were permitted.

• Presence of any active AIDS-defining opportunistic infection

• History of malignancy (ever), with the exception of localized malignancies such as squamous cell or basal cell carcinoma of the skin

• Clinical evidence of pancreatitis, as determined by the clinician (at entry)

• Use of nafcillin, dicloxacillin, or any of the prohibited medications, within 30 days prior to study entry (see the protocol for a complete list of prohibited medications)

• For females, currently breastfeeding an infant at entry

• Enrolled in another clinical trial of an investigational agent, device, or vaccine

• Unlikely to adhere to the study procedures or keep appointments, in the opinion of the site investigator or designee

• Used, or anticipates using, chronic systemic immunosuppressive agents or systemic interferon (e.g., for treatment of HCV infection) within 30 days prior to study entry.

Note: Systemic corticosteroids (e.g., prednisone or equivalent up to 2 mg/kg/day) for replacement therapy or short courses (less than or equal to 30 days) were permitted. See the protocol for a complete list of prohibited medications.

• Diagnosed with current active tuberculosis and/or was currently being treated with a rifampicin-containing regimen

• Individual had any other condition, that in the opinion of the site investigator or designee, would make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving study objectives

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Univ. of Colorado Denver NICHD CRS	Aurora	Colorado	United States	80045
2	Boston Medical Center Ped. HIV Program NICHD CRS	Boston	Massachusetts	United States	02118
3	St. Jude Children's Research Hospital CRS	Memphis	Tennessee	United States	38105-3678
4	Seattle Children's Research Institute CRS	Seattle	Washington	United States	98101
5	Soweto IMPAACT CRS	Johannesburg	Gauteng	South Africa	1862
6	Siriraj Hospital ,Mahidol University NICHD CRS	Bangkok	Bangkoknoi	Thailand	10700
7	Chiangrai Prachanukroh Hospital NICHD CRS	Chiang Mai		Thailand	50100
8	Chiang Mai University HIV Treatment (CMU HIV Treatment) CRS	Chiang Mai		Thailand	50200

Sponsors and Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

• Study Chair: Ann Melvin, MD, MPH, University of Washington, Seattle Children's Research Institute

Study Documents (Full-Text)

• Study Protocol - Apr 28, 2021
• Statistical Analysis Plan - Jun 4, 2020
• Informed Consent Form - Apr 26, 2019

More Information

Additional Information:

• Link to the IMPAACT 2014 study web page
• The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017
• Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE Manual), Version 2.0, January 2010

Publications

None provided.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT03332095
• Other Study ID Numbers: IMPAACT 2014; 34150
• First Posted: Nov 6, 2017
• Last Update Posted: Jul 7, 2022
• Last Verified: Jun 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: HIV Infections; Tenofovir; Lamivudine; Anti-Retroviral Agents

Study Results

Participant Flow

Recruitment Details	Participants were enrolled from July 2018 to February 2020. Participants were recruited from 8 medical clinics in the United States, Thailand and South Africa.
Pre-assignment Detail	There was no randomization. Enrollment started with Cohort 1, then Cohort 2 was open.

Arm/Group Title	Cohort 1: DOR	Cohort 2: DOR/3TC/TDF
Arm/Group Description	Participants received a single dose of DOR at study entry (Day 0). Doravirine (DOR): 100 mg of DOR administered orally Antiretroviral (ARV) medications: Participants in Cohort 1 received a combination of dolutegravir (DTG) or raltegravir (RAL) plus two nucleoside reverse transcriptase inhibitors (NRTIs). The ARV drugs were prescribed by participants' own health care providers and were not be provided by the study.	Participants received DOR/3TC/TDF from Day 0 through Week 96. Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (DOR/3TC/TDF): DOR/3TC/TDF administered orally as a fixed-dose combination (as a tablet, 100 mg/300 mg/300 mg) once daily
Period Title: Overall Study
STARTED	10	45
Received at Least One Dose of Study Treatment	9	45
COMPLETED	9	44
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	Cohort 1: DOR	Cohort 2: DOR/3TC/TDF	Total
Arm/Group Description	Participants received a single dose of DOR at study entry (Day 0). Doravirine (DOR): 100 mg of DOR administered orally Antiretroviral (ARV) medications: Participants in Cohort 1 received a combination of dolutegravir (DTG) or raltegravir (RAL) plus two nucleoside reverse transcriptase inhibitors (NRTIs). The ARV drugs were prescribed by participants' own health care providers and were not be provided by the study.	Participants received DOR/3TC/TDF from Day 0 through Week 96. Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (DOR/3TC/TDF): DOR/3TC/TDF administered orally as a fixed-dose combination (as a tablet, 100 mg/300 mg/300 mg) once daily	Total of all reporting groups
Overall Participants	9	45	54
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	14.3 (1.6)	15.0 (1.6)	14.9 (1.6)
Sex: Female, Male (Count of Participants)
Female	2 22.2%	26 57.8%	28 51.9%
Male	7 77.8%	19 42.2%	26 48.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	1 2.2%	1 1.9%
Not Hispanic or Latino	9 100%	44 97.8%	53 98.1%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	35 77.8%	35 64.8%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	7 77.8%	10 22.2%	17 31.5%
White	2 22.2%	0 0%	2 3.7%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	55.9 (15.8)	53.8 (8.0)	54.1 (9.5)
Weight Band (kg) (Count of Participants)
35 - <45 kg	1 11.1%	0 0%	1 1.9%
≥ 45 kg	8 88.9%	45 100%	53 98.1%
Region (Count of Participants)
Africa	0 0%	9 20%	9 16.7%
Asia/Pacific	0 0%	35 77.8%	35 64.8%
North America	9 100%	1 2.2%	10 18.5%
Class of Prior ARTs (Count of Participants)
Nucleoside Reverse Transcriptase Inhibitors (NRTI)	9 100%	43 95.6%	52 96.3%
Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI)	0 0%	32 71.1%	32 59.3%
Integrase Strand Transfer Inhibitors (INSTI)	9 100%	1 2.2%	10 18.5%
Protease Inhibitors (PI)	0 0%	10 22.2%	10 18.5%
Not Applicable	0 0%	2 4.4%	2 3.7%
Baseline Plasma HIV-1 RNA (copies/mL) (Count of Participants)
0 - <40	9 100%	43 95.6%	52 96.3%
40 - <500,000	0 0%	0 0%	0 0%
500,000 - <1,000,000	0 0%	2 4.4%	2 3.7%
Duration of Prior ARTs (days) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [days]	614.2 (511.3)	1882.3 (1649.6)	1662.8 (1589.4)
CD4 Cell Count (cells/mm^3) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cells/mm^3]	788.2 (203.9)	717.8 (283.1)	729.7 (270.9)
CD4 Percent (percent) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percent]	36.2 (5.4)	33.1 (9.1)	33.6 (8.6)
HIV-1 log10 RNA (log10 copies/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [log10 copies/mL]	1.6 (0.0)	1.8 (0.9)	1.7 (0.8)

Outcome Measures

1. Primary Outcome

Title	Pharmacokinetic (PK) Parameter: Single-dose Area-under-the-curve (AUC0-∞) of Doravirine (DOR) (Cohort 1)
Description	Pharmacokinetic parameters were determined from plasma concentration-time profiles using non-compartmental methods (WinNonlin version 6.3, Pharsight Corp., Mountain View, CA). Area under the curve (AUC) was determined using non-compartmental analyses and estimated by the linear up/log down trapezoidal rule, from time zero to infinity. Steady state AUC0-24 is equivalent to single dose AUC0-∞.
Time Frame	Measured during the entry (day 0) visit. Blood samples were drawn at pre-dose, and at 1, 2, 4, 8, 12, 24, 48 and 72 hours post-dose.

Outcome Measure Data

Analysis Population Description

Cohort 1 participants who received the study treatment.

Arm/Group Title	Cohort 1: DOR	Cohort 2: DOR/3TC/TDF
Arm/Group Description	Participants received a single dose of DOR at study entry (Day 0). Doravirine (DOR): 100 mg of DOR administered orally Antiretroviral (ARV) medications: Participants in Cohort 1 received a combination of dolutegravir (DTG) or raltegravir (RAL) plus two nucleoside reverse transcriptase inhibitors (NRTIs). The ARV drugs were prescribed by participants' own health care providers and were not be provided by the study.	Participants received DOR/3TC/TDF from Day 0 through Week 96. Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (DOR/3TC/TDF): DOR/3TC/TDF administered orally as a fixed-dose combination (as a tablet, 100 mg/300 mg/300 mg) once daily
Measure Participants	9	0
Geometric Mean (Geometric Coefficient of Variation) [µM*hr]	34.8 (43.2)

2. Primary Outcome

Title	PK Parameter: Single-dose Maximum Concentration (Cmax) of DOR (Cohort 1)
Description	Pharmacokinetic parameters were determined from plasma concentration-time profiles using non-compartmental methods (WinNonlin, version 6.3, Pharsight Corp., Mountain View, CA).
Time Frame	Measured during the entry (day 0) visit. Blood samples were drawn at pre-dose, and at 1, 2, 4, 8, 12, 24, 48 and 72 hours post-dose.

Outcome Measure Data

Analysis Population Description

Cohort 1 participants who received the study treatment.

Arm/Group Title	Cohort 1: DOR	Cohort 2: DOR/3TC/TDF
Arm/Group Description	Participants received a single dose of DOR at study entry (Day 0). Doravirine (DOR): 100 mg of DOR administered orally Antiretroviral (ARV) medications: Participants in Cohort 1 received a combination of dolutegravir (DTG) or raltegravir (RAL) plus two nucleoside reverse transcriptase inhibitors (NRTIs). The ARV drugs were prescribed by participants' own health care providers and were not be provided by the study.	Participants received DOR/3TC/TDF from Day 0 through Week 96. Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (DOR/3TC/TDF): DOR/3TC/TDF administered orally as a fixed-dose combination (as a tablet, 100 mg/300 mg/300 mg) once daily
Measure Participants	9	0
Geometric Mean (Geometric Coefficient of Variation) [µM]	2.14 (25.9)

3. Primary Outcome

Title	PK Parameter: Single-dose 24 Hour-concentration (C24hr) of DOR (Cohort 1)
Description	Pharmacokinetic parameters were determined from plasma concentration-time profiles using non-compartmental methods (WinNonlin, version 6.3, Pharsight Corp., Mountain View, CA).
Time Frame	Measured during the entry (day 0) visit. Blood samples were drawn at pre-dose, and at 1, 2, 4, 8, 12, 24, 48 and 72 hours post-dose.

Outcome Measure Data

Analysis Population Description

Cohort 1 participants who received the study treatment.

Arm/Group Title	Cohort 1: DOR	Cohort 2: DOR/3TC/TDF
Arm/Group Description	Participants received a single dose of DOR at study entry (Day 0). Doravirine (DOR): 100 mg of DOR administered orally Antiretroviral (ARV) medications: Participants in Cohort 1 received a combination of dolutegravir (DTG) or raltegravir (RAL) plus two nucleoside reverse transcriptase inhibitors (NRTIs). The ARV drugs were prescribed by participants' own health care providers and were not be provided by the study.	Participants received DOR/3TC/TDF from Day 0 through Week 96. Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (DOR/3TC/TDF): DOR/3TC/TDF administered orally as a fixed-dose combination (as a tablet, 100 mg/300 mg/300 mg) once daily
Measure Participants	9	0
Geometric Mean (Geometric Coefficient of Variation) [nM]	514 (56.5)

4. Primary Outcome

Title	Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) Assessed as Related to Study Drug
Description	Percentage and Clopper-Pearson 95% Confidence Interval (CI) of participants with Grade 3 or higher AEs judged by the medical clinic as related to the study drug. AEs were graded based on the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017 (see References).
Time Frame	Cohort 1: Measured from Day 0 through Week 2; Cohort 2: Measured from Day 0 through Week 24.

Outcome Measure Data

Analysis Population Description

Study participants who received at least one dose of study treatment were included.

Arm/Group Title	Cohort 1: DOR	Cohort 2: DOR/3TC/TDF
Arm/Group Description	Participants received a single dose of DOR at study entry (Day 0). Doravirine (DOR): 100 mg of DOR administered orally Antiretroviral (ARV) medications: Participants in Cohort 1 received a combination of dolutegravir (DTG) or raltegravir (RAL) plus two nucleoside reverse transcriptase inhibitors (NRTIs). The ARV drugs were prescribed by participants' own health care providers and were not be provided by the study.	Participants received DOR/3TC/TDF from Day 0 through Week 96. Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (DOR/3TC/TDF): DOR/3TC/TDF administered orally as a fixed-dose combination (as a tablet, 100 mg/300 mg/300 mg) once daily
Measure Participants	9	45
Number (95% Confidence Interval) [percentage of participants]	0 0%	0 0%

5. Primary Outcome

Title	Percentage of Participants With Serious Adverse Events (SAEs) Assessed as Related to Study Drug
Description	Percentage and Clopper-Pearson 95% CI of participants with SAEs judged by the medical clinic as related to the study drug. SAEs were reported according to Version 2.0 of the Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE Manual) (see references).
Time Frame	Cohort 1: Measured from Day 0 through Week 2; Cohort 2: Measured from Day 0 through Week 24.

Outcome Measure Data

Analysis Population Description

Study participants who received at least one dose of study treatment were included.

Arm/Group Title	Cohort 1: DOR	Cohort 2: DOR/3TC/TDF
Arm/Group Description	Participants received a single dose of DOR at study entry (Day 0). Doravirine (DOR): 100 mg of DOR administered orally Antiretroviral (ARV) medications: Participants in Cohort 1 received a combination of dolutegravir (DTG) or raltegravir (RAL) plus two nucleoside reverse transcriptase inhibitors (NRTIs). The ARV drugs were prescribed by participants' own health care providers and were not be provided by the study.	Participants received DOR/3TC/TDF from Day 0 through Week 96. Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (DOR/3TC/TDF): DOR/3TC/TDF administered orally as a fixed-dose combination (as a tablet, 100 mg/300 mg/300 mg) once daily
Measure Participants	9	45
Number (95% Confidence Interval) [percentage of participants]	0 0%	0 0%

6. Primary Outcome

Title	Percentage of Participants With Permanent Discontinuation of Study Drug Due to Adverse Events Assessed as Related to Study Drug
Description	Percentage and Clopper-Pearson 95% CI of participants with permanent discontinuation of study drug due to AEs judged by the medical clinic as related to the study drug.
Time Frame	Cohort 1: Measured from Day 0 through Week 2; Cohort 2: Measured from Day 0 through Week 24.

Outcome Measure Data

Analysis Population Description

Study Participants who received at least one dose of study treatment were included.

Arm/Group Title	Cohort 1: DOR	Cohort 2: DOR/3TC/TDF
Arm/Group Description	Participants received a single dose of DOR at study entry (Day 0). Doravirine (DOR): 100 mg of DOR administered orally Antiretroviral (ARV) medications: Participants in Cohort 1 received a combination of dolutegravir (DTG) or raltegravir (RAL) plus two nucleoside reverse transcriptase inhibitors (NRTIs). The ARV drugs were prescribed by participants' own health care providers and were not be provided by the study.	Participants received DOR/3TC/TDF from Day 0 through Week 96. Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (DOR/3TC/TDF): DOR/3TC/TDF administered orally as a fixed-dose combination (as a tablet, 100 mg/300 mg/300 mg) once daily
Measure Participants	9	45
Number (95% Confidence Interval) [percentage of participants]	0 0%	0 0%

7. Primary Outcome

Title	Percentage of Participants With Grade 5 Adverse Events (Death) Regardless of Relationship to Study Drug
Description	Percentage and Clopper-Pearson 95% CI of participants with Grade 5 AEs (death) regardless of relationship to study drug.
Time Frame	Cohort 1: Measured from Day 0 through Week 2; Cohort 2: Measured from Day 0 through Week 24.

Outcome Measure Data

Analysis Population Description

Study participants who received at least one dose of study treatment were included.

Arm/Group Title	Cohort 1: DOR	Cohort 2: DOR/3TC/TDF
Arm/Group Description	Participants received a single dose of DOR at study entry (Day 0). Doravirine (DOR): 100 mg of DOR administered orally Antiretroviral (ARV) medications: Participants in Cohort 1 received a combination of dolutegravir (DTG) or raltegravir (RAL) plus two nucleoside reverse transcriptase inhibitors (NRTIs). The ARV drugs were prescribed by participants' own health care providers and were not be provided by the study.	Participants received DOR/3TC/TDF from Day 0 through Week 96. Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (DOR/3TC/TDF): DOR/3TC/TDF administered orally as a fixed-dose combination (as a tablet, 100 mg/300 mg/300 mg) once daily
Measure Participants	9	45
Number (95% Confidence Interval) [percentage of participants]	0 0%	0 0%

8. Secondary Outcome

Title	PK Parameter: AUC0-24hr of DOR (Cohort 2)
Description	Pharmacokinetic parameters were determined from plasma concentration-time profiles using non-compartmental methods (WinNonlin, version 6.3, Pharsight Corp., Mountain View, CA). Area under the curve (AUC) was determined using non-compartmental analyses and estimated by the linear up/log down trapezoidal rule, from time zero to 24 hours. Intensive PK samples were collected for the first ten participants enrolled in Cohort 2.
Time Frame	Measured at Week 1 visit. Blood samples were drawn at pre-dose, and at 2, 4, 12 and 24 hours post-dose.

Outcome Measure Data

Analysis Population Description

The first 10 participants enrolled in Cohort 2.

Arm/Group Title	Cohort 1: DOR	Cohort 2: DOR/3TC/TDF
Arm/Group Description	Participants received a single dose of DOR at study entry (Day 0). Doravirine (DOR): 100 mg of DOR administered orally Antiretroviral (ARV) medications: Participants in Cohort 1 received a combination of dolutegravir (DTG) or raltegravir (RAL) plus two nucleoside reverse transcriptase inhibitors (NRTIs). The ARV drugs were prescribed by participants' own health care providers and were not be provided by the study.	Participants received DOR/3TC/TDF from Day 0 through Week 96. Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (DOR/3TC/TDF): DOR/3TC/TDF administered orally as a fixed-dose combination (as a tablet, 100 mg/300 mg/300 mg) once daily
Measure Participants	0	10
Geometric Mean (Geometric Coefficient of Variation) [µM*hr]	22.9 (47.0)

9. Secondary Outcome

Title	PK Parameter: AUC0-24hr of 3TC (Cohort 2)
Description	Pharmacokinetic parameters were determined from plasma concentration-time profiles using non-compartmental methods (WinNonlin, version 6.3, Pharsight Corp., Mountain View, CA). Area under the curve (AUC) was determined using non-compartmental analyses and estimated by the linear up/log down trapezoidal rule, from time zero to 24 hours. Intensive PK samples were collected for the first ten participants enrolled in Cohort 2.
Time Frame	Measured at Week 1 visit. Blood samples were drawn at pre-dose, and at 1, 2, 4, 8, 12 and 24 hours post-dose.

Outcome Measure Data

Analysis Population Description

The first 10 participants enrolled in Cohort 2.

Arm/Group Title	Cohort 1: DOR	Cohort 2: DOR/3TC/TDF
Arm/Group Description	Participants received a single dose of DOR at study entry (Day 0). Doravirine (DOR): 100 mg of DOR administered orally Antiretroviral (ARV) medications: Participants in Cohort 1 received a combination of dolutegravir (DTG) or raltegravir (RAL) plus two nucleoside reverse transcriptase inhibitors (NRTIs). The ARV drugs were prescribed by participants' own health care providers and were not be provided by the study.	Participants received DOR/3TC/TDF from Day 0 through Week 96. Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (DOR/3TC/TDF): DOR/3TC/TDF administered orally as a fixed-dose combination (as a tablet, 100 mg/300 mg/300 mg) once daily
Measure Participants	0	10
Geometric Mean (Geometric Coefficient of Variation) [h.ng/mL]	11300 (27.9)

10. Secondary Outcome

Title	PK Parameter: AUC0-24hr of Tenofovir (Cohort 2)
Description	Pharmacokinetic parameters were determined from plasma concentration-time profiles using non-compartmental methods (WinNonlin, version 6.3, Pharsight Corp., Mountain View, CA). Area under the curve (AUC) was determined using non-compartmental analyses and estimated by the linear up/log down trapezoidal rule, from time zero to 24 hours. Intensive PK samples were collected for the first ten participants enrolled in Cohort 2.
Time Frame	Measured at Week 1 visit. Blood samples were drawn at pre-dose, and at 1, 2, 4, 8, 12 and 24 hours post-dose.

Outcome Measure Data

Analysis Population Description

The first 10 participants enrolled in Cohort 2.

Arm/Group Title	Cohort 1: DOR	Cohort 2: DOR/3TC/TDF
Arm/Group Description	Participants received a single dose of DOR at study entry (Day 0). Doravirine (DOR): 100 mg of DOR administered orally Antiretroviral (ARV) medications: Participants in Cohort 1 received a combination of dolutegravir (DTG) or raltegravir (RAL) plus two nucleoside reverse transcriptase inhibitors (NRTIs). The ARV drugs were prescribed by participants' own health care providers and were not be provided by the study.	Participants received DOR/3TC/TDF from Day 0 through Week 96. Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (DOR/3TC/TDF): DOR/3TC/TDF administered orally as a fixed-dose combination (as a tablet, 100 mg/300 mg/300 mg) once daily
Measure Participants	0	10
Geometric Mean (Geometric Coefficient of Variation) [h.ng/mL]	2550 (14.3)

11. Secondary Outcome

Title	PK Parameter: Cmax of DOR (Cohort 2)
Description	Pharmacokinetic parameters were determined from plasma concentration-time profiles using non-compartmental methods (WinNonlin, version 6.3, Pharsight Corp., Mountain View, CA). Cmax was projected from individual plasma concentration-time profiles using the non-parametric superposition function in WinNonLin v6.3. Intensive PK samples were collected for the first ten participants enrolled in Cohort 2.
Time Frame	Measured at Week 1 visit. Blood samples were drawn at pre-dose, and at 2, 4, 12 and 24 hours post-dose.

Outcome Measure Data

Analysis Population Description

The first 10 participants enrolled in Cohort 2.

Arm/Group Title	Cohort 1: DOR	Cohort 2: DOR/3TC/TDF
Arm/Group Description	Participants received a single dose of DOR at study entry (Day 0). Doravirine (DOR): 100 mg of DOR administered orally Antiretroviral (ARV) medications: Participants in Cohort 1 received a combination of dolutegravir (DTG) or raltegravir (RAL) plus two nucleoside reverse transcriptase inhibitors (NRTIs). The ARV drugs were prescribed by participants' own health care providers and were not be provided by the study.	Participants received DOR/3TC/TDF from Day 0 through Week 96. Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (DOR/3TC/TDF): DOR/3TC/TDF administered orally as a fixed-dose combination (as a tablet, 100 mg/300 mg/300 mg) once daily
Measure Participants	0	10
Geometric Mean (Geometric Coefficient of Variation) [µM]	2.13 (42.7)

12. Secondary Outcome

Title	PK Parameter: Cmax of 3TC (Cohort 2)
Description	Pharmacokinetic parameters were determined from plasma concentration-time profiles using non-compartmental methods (WinNonlin, version 6.3, Pharsight Corp., Mountain View, CA). Cmax was projected from individual plasma concentration-time profiles using the non-parametric superposition function in WinNonLin v6.3. Intensive PK samples were collected for the first ten participants enrolled in Cohort 2.
Time Frame	Measured at Week 1 visit. Blood samples were drawn at pre-dose, and at 1, 2, 4, 8, 12 and 24 hours post-dose.

Outcome Measure Data

Analysis Population Description

The first 10 participants enrolled in Cohort 2.

Arm/Group Title	Cohort 1: DOR	Cohort 2: DOR/3TC/TDF
Arm/Group Description	Participants received a single dose of DOR at study entry (Day 0). Doravirine (DOR): 100 mg of DOR administered orally Antiretroviral (ARV) medications: Participants in Cohort 1 received a combination of dolutegravir (DTG) or raltegravir (RAL) plus two nucleoside reverse transcriptase inhibitors (NRTIs). The ARV drugs were prescribed by participants' own health care providers and were not be provided by the study.	Participants received DOR/3TC/TDF from Day 0 through Week 96. Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (DOR/3TC/TDF): DOR/3TC/TDF administered orally as a fixed-dose combination (as a tablet, 100 mg/300 mg/300 mg) once daily
Measure Participants	0	10
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	2100 (23.6)

13. Secondary Outcome

Title	PK Parameter: Cmax of Tenofovir (Cohort 2)
Description	Pharmacokinetic parameters were determined from plasma concentration-time profiles using non-compartmental methods (WinNonlin, version 6.3, Pharsight Corp., Mountain View, CA). Cmax was projected from individual plasma concentration-time profiles using the non-parametric superposition function in WinNonLin v6.3. Intensive PK samples were collected for the first ten participants enrolled in Cohort 2.
Time Frame	Measured at Week 1 visit. Blood samples were drawn at pre-dose, and at 1, 2, 4, 8, 12 and 24 hours post-dose.

Outcome Measure Data

Analysis Population Description

The first 10 participants enrolled in Cohort 2.

Arm/Group Title	Cohort 1: DOR	Cohort 2: DOR/3TC/TDF
Arm/Group Description	Participants received a single dose of DOR at study entry (Day 0). Doravirine (DOR): 100 mg of DOR administered orally Antiretroviral (ARV) medications: Participants in Cohort 1 received a combination of dolutegravir (DTG) or raltegravir (RAL) plus two nucleoside reverse transcriptase inhibitors (NRTIs). The ARV drugs were prescribed by participants' own health care providers and were not be provided by the study.	Participants received DOR/3TC/TDF from Day 0 through Week 96. Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (DOR/3TC/TDF): DOR/3TC/TDF administered orally as a fixed-dose combination (as a tablet, 100 mg/300 mg/300 mg) once daily
Measure Participants	0	10
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	293 (36.6)

14. Secondary Outcome

Title	PK Parameter: C24hr of DOR (Cohort 2)
Description	Pharmacokinetic parameters were determined from plasma concentration-time profiles using non-compartmental methods (WinNonlin, version 6.3, Pharsight Corp., Mountain View, CA). C24hr was projected from individual plasma concentration-time profiles using the non-parametric superposition function in WinNonLin v6.3. Intensive PK samples were collected for the first ten participants enrolled in Cohort 2.
Time Frame	Measured at Week 1 visit. Blood samples were drawn at pre-dose, and at 2, 4, 12 and 24 hours post-dose.

Outcome Measure Data

Analysis Population Description

The first 10 participants enrolled in Cohort 2.

Arm/Group Title	Cohort 1: DOR	Cohort 2: DOR/3TC/TDF
Arm/Group Description	Participants received a single dose of DOR at study entry (Day 0). Doravirine (DOR): 100 mg of DOR administered orally Antiretroviral (ARV) medications: Participants in Cohort 1 received a combination of dolutegravir (DTG) or raltegravir (RAL) plus two nucleoside reverse transcriptase inhibitors (NRTIs). The ARV drugs were prescribed by participants' own health care providers and were not be provided by the study.	Participants received DOR/3TC/TDF from Day 0 through Week 96. Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (DOR/3TC/TDF): DOR/3TC/TDF administered orally as a fixed-dose combination (as a tablet, 100 mg/300 mg/300 mg) once daily
Measure Participants	0	10
Geometric Mean (Geometric Coefficient of Variation) [nM]	282 (73.8)

15. Secondary Outcome

Title	PK Parameter: C24hr of 3TC (Cohort 2)
Description	Pharmacokinetic parameters were determined from plasma concentration-time profiles using non-compartmental methods (WinNonlin, version 6.3, Pharsight Corp., Mountain View, CA). C24hr was projected from individual plasma concentration-time profiles using the non-parametric superposition function in WinNonLin v6.3. Intensive PK samples were collected for the first ten participants enrolled in Cohort 2.
Time Frame	Measured at Week 1 visit. Blood samples were drawn at pre-dose, and at 1, 2, 4, 8, 12 and 24 hours post-dose.

Outcome Measure Data

Analysis Population Description

The first 10 participants enrolled in Cohort 2.

Arm/Group Title	Cohort 1: DOR	Cohort 2: DOR/3TC/TDF
Arm/Group Description	Participants received a single dose of DOR at study entry (Day 0). Doravirine (DOR): 100 mg of DOR administered orally Antiretroviral (ARV) medications: Participants in Cohort 1 received a combination of dolutegravir (DTG) or raltegravir (RAL) plus two nucleoside reverse transcriptase inhibitors (NRTIs). The ARV drugs were prescribed by participants' own health care providers and were not be provided by the study.	Participants received DOR/3TC/TDF from Day 0 through Week 96. Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (DOR/3TC/TDF): DOR/3TC/TDF administered orally as a fixed-dose combination (as a tablet, 100 mg/300 mg/300 mg) once daily
Measure Participants	0	10
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	66.3 (54.7)

16. Secondary Outcome

Title	PK Parameter: C24hr of Tenofovir (Cohort 2)
Description	Pharmacokinetic parameters were determined from plasma concentration-time profiles using non-compartmental methods (WinNonlin, version 6.3, Pharsight Corp., Mountain View, CA). C24hr was projected from individual plasma concentration-time profiles using the non-parametric superposition function in WinNonLin v6.3. Intensive PK samples were collected for the first ten participants enrolled in Cohort 2.
Time Frame	Measured at Week 1 visit. Blood samples were drawn at pre-dose, and at 1, 2, 4, 8, 12 and 24 hours post-dose.

Outcome Measure Data

Analysis Population Description

The first 10 participants enrolled in Cohort 2.

Arm/Group Title	Cohort 1: DOR	Cohort 2: DOR/3TC/TDF
Arm/Group Description	Participants received a single dose of DOR at study entry (Day 0). Doravirine (DOR): 100 mg of DOR administered orally Antiretroviral (ARV) medications: Participants in Cohort 1 received a combination of dolutegravir (DTG) or raltegravir (RAL) plus two nucleoside reverse transcriptase inhibitors (NRTIs). The ARV drugs were prescribed by participants' own health care providers and were not be provided by the study.	Participants received DOR/3TC/TDF from Day 0 through Week 96. Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (DOR/3TC/TDF): DOR/3TC/TDF administered orally as a fixed-dose combination (as a tablet, 100 mg/300 mg/300 mg) once daily
Measure Participants	0	10
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	50.2 (9.4)

17. Secondary Outcome

Title	Percentage of Participants With Plasma HIV-1 RNA Less Than 200 Copies/mL at Week 24 (Cohort 2)
Description	Virologic responses were assessed at week 24 as percentage (%) of participants and Clopper-Pearson 95% CI. Missing values were considered as failures for participants with missing data due to discontinuation of study drug as a result of virologic failure or for non-treatment related reasons with last available RNA >200 copies/mL; otherwise participants with missing values were excluded.
Time Frame	Measured at week 24.

Outcome Measure Data

Analysis Population Description

Cohort 2 participants who received at least one dose of study treatment. Participants who discontinued study for reasons other than virologic failure were excluded.

Arm/Group Title	Cohort 1: DOR	Cohort 2: DOR/3TC/TDF
Arm/Group Description	Participants received a single dose of DOR at study entry (Day 0). Doravirine (DOR): 100 mg of DOR administered orally Antiretroviral (ARV) medications: Participants in Cohort 1 received a combination of dolutegravir (DTG) or raltegravir (RAL) plus two nucleoside reverse transcriptase inhibitors (NRTIs). The ARV drugs were prescribed by participants' own health care providers and were not be provided by the study.	Participants received DOR/3TC/TDF from Day 0 through Week 96. Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (DOR/3TC/TDF): DOR/3TC/TDF administered orally as a fixed-dose combination (as a tablet, 100 mg/300 mg/300 mg) once daily
Measure Participants	0	44
Number (95% Confidence Interval) [Percentage of participants]	97.7 1085.6%

18. Secondary Outcome

Title	Percentage of Participants With Plasma HIV-1 RNA Less Than 200 Copies/mL at Week 48 (Cohort 2)
Description	Virologic responses were assessed at week 48 as percentage (%) of participants and Clopper-Pearson 95% CI. Missing values were considered as failures for participants with missing data due to discontinuation of study drug as a result of virologic failure or for non-treatment related reasons with last available RNA >200 copies/mL; otherwise participants with missing values were excluded. The study is ongoing and the participants are still in follow up (post PCD). Results will be added at the end of the study follow-up.
Time Frame	Measured at week 48.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

19. Secondary Outcome

Title	Percentage of Participants With Plasma HIV-1 RNA Less Than 200 Copies/mL at Week 96 (Cohort 2)
Description	Virologic responses were assessed at week 96 as percentage (%) of participants and Clopper-Pearson 95% CI. Missing values were considered as failures for participants with missing data due to discontinuation of study drug as a result of virologic failure or for non-treatment related reasons with last available RNA >200 copies/mL; otherwise participants with missing values were excluded. The study is ongoing and the participants are still in follow up (post PCD). Results will be added at the end of the study follow-up.
Time Frame	Measured at week 96.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

20. Secondary Outcome

Title	Percentage of Participants With Plasma HIV-1 RNA Less Than 50 Copies/mL at Week 24 (Cohort 2)
Description	Virologic responses were assessed at week 24 as percentage of participants and Clopper-Pearson 95% CI. Missing values were considered as failures for participants with missing data due to discontinuation of study drug as a result of virologic failure or for non-treatment related reasons with last available RNA >50 copies/mL. Otherwise participants with missing values were excluded.
Time Frame	Measured at week 24.

Outcome Measure Data

Analysis Population Description

Cohort 2 participants who received at least one dose of study treatment. Participants who discontinued study for reasons other than virologic failure were excluded. One participant whose sample was diluted due to low volume, resulting in increased assay limit of quantification from 40 to 200 copies/mL was excluded.

Arm/Group Title	Cohort 1: DOR	Cohort 2: DOR/3TC/TDF
Arm/Group Description	Participants received a single dose of DOR at study entry (Day 0). Doravirine (DOR): 100 mg of DOR administered orally Antiretroviral (ARV) medications: Participants in Cohort 1 received a combination of dolutegravir (DTG) or raltegravir (RAL) plus two nucleoside reverse transcriptase inhibitors (NRTIs). The ARV drugs were prescribed by participants' own health care providers and were not be provided by the study.	Participants received DOR/3TC/TDF from Day 0 through Week 96. Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (DOR/3TC/TDF): DOR/3TC/TDF administered orally as a fixed-dose combination (as a tablet, 100 mg/300 mg/300 mg) once daily
Measure Participants	0	43
Number (95% Confidence Interval) [Percentage of participants]	97.7 1085.6%

21. Secondary Outcome

Title	Percentage of Participants With Plasma HIV-1 RNA Less Than 50 Copies/mL at Week 48 (Cohort 2)
Description	Virologic responses were assessed at week 48 as percentage of participants and Clopper-Pearson 95% CI. Missing values were considered as failures for participants with missing data due to discontinuation of study drug as a result of virologic failure or for non-treatment related reasons with last available RNA >50 copies/mL. Otherwise participants with missing values were excluded. The study is ongoing and the participants are still in follow up (post PCD). Results will be added at the end of the study follow-up.
Time Frame	Measured at week 48.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

22. Secondary Outcome

Title	Percentage of Participants With Plasma HIV-1 RNA Less Than 50 Copies/mL at Week 96 (Cohort 2)
Description	Virologic responses were assessed at week 96 as percentage of participants and Clopper-Pearson 95% CI. Missing values were considered as failures for participants with missing data due to discontinuation of study drug as a result of virologic failure or for non-treatment related reasons with last available RNA >50 copies/mL. Otherwise participants with missing values were excluded. The study is ongoing and the participants are still in follow up (post PCD). Results will be added at the end of the study follow-up.
Time Frame	Measured at week 96.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

23. Secondary Outcome

Title	Percentage of Participants With Plasma HIV-1 RNA Less Than 40 Copies/mL at Week 24 (Cohort 2)
Description	Virologic responses were assessed at week 24 as percentage (%) of participants and Clopper-Pearson 95% CI. Missing values were considered as failures for participants with missing data due to discontinuation of study drug as a result of virologic failure or for non-treatment related reasons with last available RNA >40 copies/mL; Otherwise participants with missing values were excluded.
Time Frame	Measured at week 24.

Outcome Measure Data

Analysis Population Description

Cohort 2 participants who received at least one dose of study treatment. Participants who discontinued study for reasons other than virologic failure were excluded. One participant whose sample was diluted due to low volume, resulting in increased assay limit of quantification from 40 to 200 copies/mL was excluded.

Arm/Group Title	Cohort 1: DOR	Cohort 2: DOR/3TC/TDF
Arm/Group Description	Participants received a single dose of DOR at study entry (Day 0). Doravirine (DOR): 100 mg of DOR administered orally Antiretroviral (ARV) medications: Participants in Cohort 1 received a combination of dolutegravir (DTG) or raltegravir (RAL) plus two nucleoside reverse transcriptase inhibitors (NRTIs). The ARV drugs were prescribed by participants' own health care providers and were not be provided by the study.	Participants received DOR/3TC/TDF from Day 0 through Week 96. Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (DOR/3TC/TDF): DOR/3TC/TDF administered orally as a fixed-dose combination (as a tablet, 100 mg/300 mg/300 mg) once daily
Measure Participants	0	43
Number (95% Confidence Interval) [Percentage of participants]	97.7 1085.6%

24. Secondary Outcome

Title	Percentage of Participants With Plasma HIV-1 RNA Less Than 40 Copies/mL at Week 48 (Cohort 2)
Description	Virologic responses were assessed at week 48 as percentage (%) of participants and Clopper-Pearson 95% CI. Missing values were considered as failures for participants with missing data due to discontinuation of study drug as a result of virologic failure or for non-treatment related reasons with last available RNA >40 copies/mL; Otherwise participants with missing values were excluded. The study is ongoing and the participants are still in follow up (post PCD). Results will be added at the end of the study follow-up.
Time Frame	Measured at week 48.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

25. Secondary Outcome

Title	Percentage of Participants With Plasma HIV-1 RNA Less Than 40 Copies/mL at Week 96 (Cohort 2)
Description	Virologic responses were assessed at week 96 as percentage (%) of participants and Clopper-Pearson 95% CI. Missing values were considered as failures for participants with missing data due to discontinuation of study drug as a result of virologic failure or for non-treatment related reasons with last available RNA >40 copies/mL; Otherwise participants with missing values were excluded. The study is ongoing and the participants are still in follow up (post PCD). Results will be added at the end of the study follow-up.
Time Frame	Measured at week 96.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

26. Secondary Outcome

Title	Summary of log10 Drop From Baseline to Week 24 in Plasma HIV-1 RNA (ART-naive Participants) (Cohort 2)
Description	The differences between log10 HIV RNA at Week 24 minus at the Day 0 are summarized.
Time Frame	Measured at Day 0 and week 24.

Outcome Measure Data

Analysis Population Description

Cohort 2 participants who were ART-naive.

Arm/Group Title	Cohort 1: DOR	Cohort 2: DOR/3TC/TDF
Arm/Group Description	Participants received a single dose of DOR at study entry (Day 0). Doravirine (DOR): 100 mg of DOR administered orally Antiretroviral (ARV) medications: Participants in Cohort 1 received a combination of dolutegravir (DTG) or raltegravir (RAL) plus two nucleoside reverse transcriptase inhibitors (NRTIs). The ARV drugs were prescribed by participants' own health care providers and were not be provided by the study.	Participants received DOR/3TC/TDF from Day 0 through Week 96. Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (DOR/3TC/TDF): DOR/3TC/TDF administered orally as a fixed-dose combination (as a tablet, 100 mg/300 mg/300 mg) once daily
Measure Participants	0	2
Mean (95% Confidence Interval) [Log10 plasma HIV-1 RNA]	-2.6

27. Secondary Outcome

Title	Summary of log10 Drop From Baseline to Week 48 in Plasma HIV-1 RNA (ART-naive Participants) (Cohort 2)
Description	The differences between log10 HIV RNA at Week 48 minus at the Day 0 are summarized. The study is ongoing and the participants are still in follow up (post PCD). Results will be added at the end of the study follow-up.
Time Frame	Measured at Day 0 and week 48.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

28. Secondary Outcome

Title	Summary of log10 Drop From Baseline to Week 96 in Plasma HIV-1 RNA (ART-naive Participants) (Cohort 2)
Description	The differences between log10 HIV RNA at Week 96 minus at the Day 0 are summarized. The study is ongoing and the participants are still in follow up (post PCD). Results will be added at the end of the study follow-up.
Time Frame	Measured at Day 0 and week 96.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

29. Secondary Outcome

Title	Summary of Changes in CD4 Count From Baseline to Week 24 (Cohort 2)
Description	The mean differences between CD4 count at Week 24 minus at the Day 0, and 95% Clopper-Pearson CI, are presented.
Time Frame	Measured at Day 0 and week 24.

Outcome Measure Data

Analysis Population Description

Cohort 2 participants who had non-missing values at both Day 0 and Week 24 timepoints.

Arm/Group Title	Cohort 1: DOR	Cohort 2: DOR/3TC/TDF
Arm/Group Description	Participants received a single dose of DOR at study entry (Day 0). Doravirine (DOR): 100 mg of DOR administered orally Antiretroviral (ARV) medications: Participants in Cohort 1 received a combination of dolutegravir (DTG) or raltegravir (RAL) plus two nucleoside reverse transcriptase inhibitors (NRTIs). The ARV drugs were prescribed by participants' own health care providers and were not be provided by the study.	Participants received DOR/3TC/TDF from Day 0 through Week 96. Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (DOR/3TC/TDF): DOR/3TC/TDF administered orally as a fixed-dose combination (as a tablet, 100 mg/300 mg/300 mg) once daily
Measure Participants	0	43
Mean (95% Confidence Interval) [cells/mm^3]	84.8

30. Secondary Outcome

Title	Summary of Changes in CD4 Count From Baseline to Week 48 (Cohort 2)
Description	The mean differences between CD4 count at Week 48 minus at the Day 0, and 95% Clopper-Pearson CI, are presented. The study is ongoing and the participants are still in follow up (post PCD). Results will be added at the end of the study follow-up.
Time Frame	Measured at Day 0 and week 48.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

31. Secondary Outcome

Title	Summary of Changes in CD4 Count From Baseline to Week 96 (Cohort 2)
Description	The mean differences between CD4 count at Week 96 minus at the Day 0, and 95% Clopper-Pearson CI, are presented. The study is ongoing and the participants are still in follow up (post PCD). Results will be added at the end of the study follow-up.
Time Frame	Measured at Day 0 and week 96.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

32. Secondary Outcome

Title	Summary of Changes in CD4 Percent From Baseline to Week 24 (Cohort 2)
Description	The mean differences between CD4 percent at Week 24 minus at the Day 0, and 95% Clopper-Pearson CI, are presented.
Time Frame	Measured at Day 0 and week 24.

Outcome Measure Data

Analysis Population Description

Cohort 2 participants who had non-missing values at both Day 0 and Week 24 timepoints.

Arm/Group Title	Cohort 1: DOR	Cohort 2: DOR/3TC/TDF
Arm/Group Description	Participants received a single dose of DOR at study entry (Day 0). Doravirine (DOR): 100 mg of DOR administered orally Antiretroviral (ARV) medications: Participants in Cohort 1 received a combination of dolutegravir (DTG) or raltegravir (RAL) plus two nucleoside reverse transcriptase inhibitors (NRTIs). The ARV drugs were prescribed by participants' own health care providers and were not be provided by the study.	Participants received DOR/3TC/TDF from Day 0 through Week 96. Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (DOR/3TC/TDF): DOR/3TC/TDF administered orally as a fixed-dose combination (as a tablet, 100 mg/300 mg/300 mg) once daily
Measure Participants	0	43
Mean (95% Confidence Interval) [Percent]	-1.5

33. Secondary Outcome

Title	Summary of Changes in CD4 Percent From Baseline to Week 48 (Cohort 2)
Description	The mean differences between CD4 percent at Week 48 minus at the Day 0, and 95% Clopper-Pearson CI, are presented. The study is ongoing and the participants are still in follow up (post PCD). Results will be added at the end of the study follow-up.
Time Frame	Measured at Day 0 and week 48.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

34. Secondary Outcome

Title	Summary of Changes in CD4 Percent From Baseline to Week 96 (Cohort 2)
Description	The mean differences between CD4 percent at Week 96 minus at the Day 0, and 95% Clopper-Pearson CI, are presented. The study is ongoing and the participants are still in follow up (post PCD). Results will be added at the end of the study follow-up.
Time Frame	Measured at Day 0 and week 96.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

35. Secondary Outcome

Title	Percentage of Participants With Grade 3 or Higher Adverse Events Assessed as Related to Study Drug (Cohort 2) Through End of Study
Description	Percentage and Clopper-Pearson 95% CI of participants with Grade 3 or higher AEs judged by the medical clinic as related to the study drug. AEs were graded based on the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017 (DAIDS) AE Grading table corrected version 2.1 (see References). These results will be added at the end of the study.
Time Frame	Measured from Day 0 through Week 96.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

36. Secondary Outcome

Title	Percentage of Participants With Serious Adverse Events Assessed as Related to Study Drug (Cohort 2) Through End of Study
Description	Percentage and Clopper-Pearson 95% CI of participants with SAEs judged by the medical clinic as related to the study drug. SAEs were reported according to version 2.0 of the Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE Manual) (see references). These results will be added at the end of the study.
Time Frame	Measured from Day 0 through Week 96.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

37. Secondary Outcome

Title	Percentage of Participants With Permanent Discontinuation of Study Drug Due to Adverse Events Assessed as Related to Study Drug (Cohort 2) Through End of Study
Description	Percentage and Clopper-Pearson 95% CI of participants with permanent discontinuation of study drug due to AEs judged by the medical clinic as related to the study drug. These results will be added at the end of the study.
Time Frame	Measured from Day 0 through Week 96.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

38. Secondary Outcome

Title	Percentage of Participants With Grade 5 Adverse Events (Death) Regardless of Relationship to Study Drug (Cohort 2) Through End of Study
Description	Percentage and Clopper-Pearson 95% CI of participants with Grade 5 adverse events (death). These results will be added at the end of the study.
Time Frame	Measured from Day 0 through Week 96.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	From start of study treatment to study completion at Week 2 in Cohort 1 or at Week 24 in Cohort 2. Study is ongoing. Some participants are still in follow-up (post-PCD). AE summaries will be updated at end of study follow up (week 96).
Adverse Event Reporting Description	AEs were summarized for participants who received at least one dose, and included abnormal laboratory events with specimen collection dates greater than first dose date and AEs that are not abnormal laboratory events and have onset dates equal to or greater than study drug's first dose date. AES were restricted to those with start dates less than or equal to the PCD. AE severity grading was based on the DAIDS AE Grading Table, Corrected Version 2.1. SAE were graded using DAIDS EAE Manual V2.0.
Arm/Group Title	Cohort 1: DOR		Cohort 2: DOR/3TC/TDF
Arm/Group Description	Participants received a single dose of DOR at study entry (Day 0). Doravirine (DOR): 100 mg of DOR administered orally Antiretroviral (ARV) medications: Participants in Cohort 1 received a combination of dolutegravir (DTG) or raltegravir (RAL) plus two nucleoside reverse transcriptase inhibitors (NRTIs). The ARV drugs were prescribed by participants' own health care providers and were not be provided by the study.		Participants received DOR/3TC/TDF from Day 0 through Week 96. Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (DOR/3TC/TDF): DOR/3TC/TDF administered orally as a fixed-dose combination (as a tablet, 100 mg/300 mg/300 mg) once daily.
All Cause Mortality
	Cohort 1: DOR		Cohort 2: DOR/3TC/TDF
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		0/45 (0%)
Serious Adverse Events
	Cohort 1: DOR		Cohort 2: DOR/3TC/TDF
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		1/45 (2.2%)
Infections and infestations
Gastroenteritis	0/9 (0%)		1/45 (2.2%)
Injury, poisoning and procedural complications
Lip injury	0/9 (0%)		1/45 (2.2%)
Other (Not Including Serious) Adverse Events
	Cohort 1: DOR		Cohort 2: DOR/3TC/TDF
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/9 (44.4%)		45/45 (100%)
Blood and lymphatic system disorders
Iron deficiency anaemia	0/9 (0%)		2/45 (4.4%)
Lymphadenitis	0/9 (0%)		1/45 (2.2%)
Lymphadenopathy	0/9 (0%)		1/45 (2.2%)
Eye disorders
Conjunctival pallor	0/9 (0%)		3/45 (6.7%)
Gastrointestinal disorders
Abdominal pain	0/9 (0%)		1/45 (2.2%)
Abdominal pain upper	0/9 (0%)		1/45 (2.2%)
Aphthous ulcer	0/9 (0%)		2/45 (4.4%)
Diarrhoea	1/9 (11.1%)		3/45 (6.7%)
Dyspepsia	0/9 (0%)		1/45 (2.2%)
Flatulence	0/9 (0%)		1/45 (2.2%)
Nausea	0/9 (0%)		1/45 (2.2%)
Rectal haemorrhage	0/9 (0%)		1/45 (2.2%)
Salivary gland mucocoele	0/9 (0%)		1/45 (2.2%)
Vomiting	0/9 (0%)		1/45 (2.2%)
General disorders
Chest pain	0/9 (0%)		1/45 (2.2%)
Malaise	0/9 (0%)		2/45 (4.4%)
Pyrexia	0/9 (0%)		1/45 (2.2%)
Hepatobiliary disorders
Hyperbilirubinaemia	0/9 (0%)		2/45 (4.4%)
Infections and infestations
Bronchitis viral	0/9 (0%)		2/45 (4.4%)
Nasopharyngitis	0/9 (0%)		4/45 (8.9%)
Pharyngitis	0/9 (0%)		2/45 (4.4%)
Pharyngitis bacterial	0/9 (0%)		1/45 (2.2%)
Urinary tract infection	0/9 (0%)		2/45 (4.4%)
Injury, poisoning and procedural complications
Procedural pain	0/9 (0%)		1/45 (2.2%)
Skin abrasion	0/9 (0%)		2/45 (4.4%)
Thermal burn	0/9 (0%)		1/45 (2.2%)
Investigations
Alanine aminotransferase increased	0/9 (0%)		18/45 (40%)
Aspartate aminotransferase increased	2/9 (22.2%)		12/45 (26.7%)
Blood albumin decreased	0/9 (0%)		3/45 (6.7%)
Blood alkaline phosphatase increased	1/9 (11.1%)		9/45 (20%)
Blood bicarbonate decreased	0/9 (0%)		8/45 (17.8%)
Blood cholesterol increased	0/9 (0%)		5/45 (11.1%)
Blood creatinine increased	0/9 (0%)		13/45 (28.9%)
Blood glucose decreased	0/9 (0%)		3/45 (6.7%)
Blood glucose increased	1/9 (11.1%)		5/45 (11.1%)
Blood phosphorus decreased	0/9 (0%)		2/45 (4.4%)
Blood phosphorus increased	1/9 (11.1%)		0/45 (0%)
Blood potassium decreased	0/9 (0%)		6/45 (13.3%)
Blood potassium increased	0/9 (0%)		1/45 (2.2%)
Blood pressure increased	0/9 (0%)		6/45 (13.3%)
Blood sodium decreased	0/9 (0%)		4/45 (8.9%)
Blood triglycerides increased	0/9 (0%)		1/45 (2.2%)
Carbon dioxide decreased	0/9 (0%)		9/45 (20%)
Glomerular filtration rate decreased	0/9 (0%)		19/45 (42.2%)
Haemoglobin decreased	0/9 (0%)		5/45 (11.1%)
Lipase increased	0/9 (0%)		6/45 (13.3%)
Low density lipoprotein increased	0/9 (0%)		1/45 (2.2%)
Neutrophil count decreased	1/9 (11.1%)		0/45 (0%)
Platelet count decreased	0/9 (0%)		1/45 (2.2%)
Metabolism and nutrition disorders
Decreased appetite	0/9 (0%)		1/45 (2.2%)
Hypercholesterolaemia	0/9 (0%)		1/45 (2.2%)
Hypertriglyceridaemia	0/9 (0%)		3/45 (6.7%)
Hypocholesterolaemia	0/9 (0%)		1/45 (2.2%)
Hypokalaemia	0/9 (0%)		4/45 (8.9%)
Obesity	0/9 (0%)		1/45 (2.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/9 (0%)		1/45 (2.2%)
Joint swelling	0/9 (0%)		1/45 (2.2%)
Kyphosis	0/9 (0%)		1/45 (2.2%)
Myalgia	0/9 (0%)		1/45 (2.2%)
Pain in extremity	0/9 (0%)		1/45 (2.2%)
Nervous system disorders
Dizziness	0/9 (0%)		1/45 (2.2%)
Headache	0/9 (0%)		7/45 (15.6%)
Lethargy	0/9 (0%)		1/45 (2.2%)
Renal and urinary disorders
Dysuria	0/9 (0%)		1/45 (2.2%)
Proteinuria	0/9 (0%)		3/45 (6.7%)
Reproductive system and breast disorders
Bleeding anovulatory	0/9 (0%)		1/45 (2.2%)
Dysmenorrhoea	0/9 (0%)		1/45 (2.2%)
Oligomenorrhoea	0/9 (0%)		1/45 (2.2%)
Respiratory, thoracic and mediastinal disorders
Cough	0/9 (0%)		7/45 (15.6%)
Dysphonia	0/9 (0%)		1/45 (2.2%)
Nasal congestion	0/9 (0%)		6/45 (13.3%)
Oropharyngeal discomfort	0/9 (0%)		1/45 (2.2%)
Oropharyngeal pain	0/9 (0%)		4/45 (8.9%)
Pharyngeal erythema	0/9 (0%)		2/45 (4.4%)
Productive cough	0/9 (0%)		5/45 (11.1%)
Rhinorrhoea	0/9 (0%)		6/45 (13.3%)
Tonsillar hypertrophy	0/9 (0%)		1/45 (2.2%)
Skin and subcutaneous tissue disorders
Acne	0/9 (0%)		4/45 (8.9%)
Papule	0/9 (0%)		3/45 (6.7%)
Pruritus	0/9 (0%)		4/45 (8.9%)
Rash	0/9 (0%)		1/45 (2.2%)
Rash erythematous	0/9 (0%)		1/45 (2.2%)
Rash maculo-papular	0/9 (0%)		1/45 (2.2%)
Seborrhoeic dermatitis	0/9 (0%)		1/45 (2.2%)
Urticaria	0/9 (0%)		1/45 (2.2%)
Vascular disorders
Hypertension	0/9 (0%)		4/45 (8.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

In accordance with the Clinical Trials Agreement between NIAID (DAIDS) and company collaborators, NIAID (DAIDS) provides companies with a copy of any abstract, press release, or manuscript prior to submission for publication with sufficient time for company review and comment. The publication/other disclosure can be delayed for up to 30 additional business days for manuscripts and five (5) business days for abstracts, to preserve U.S. or foreign patent or other intellectual property rights.