A Study to Evaluate the Efficacy and Safety of (D/C/F/TAF) Once Daily Fixed Dose Combination (FDC) Regimen in Newly Diagnosed, Antiretroviral Treatment-naive Human Immunodeficiency Virus Type 1 (HIV-1) Infected Participants Receiving Care in a Test and Treat Model of Care

• ClinicalTrials.gov Identifier: NCT03227861
• Recruitment Status: Completed
• First Posted: July 24, 2017
• Results First Posted: January 7, 2020
• Last Update Posted: September 25, 2020
• Sponsor: Janssen Scientific Affairs, LLC
• Information provided by (Responsible Party): Janssen Scientific Affairs, LLC

Study Description

Brief Summary:

The purpose of this study is to assess the efficacy of Darunavir/ Cobicistat/ Emtricitabine/ Tenofovir Alafenamide (D/C/F/TAF) fixed-dose combination (FDC) in a Test and Treat model of care in newly diagnosed human immunodeficiency virus (HIV-1)-infected, treatment-naive participants as determined by the proportion of virologic responders defined as having (HIV)-1 ribonucleic acid (RNA) lesser than 50 copies per milliliter (copies/mL) at Week 48.

Condition or disease	Intervention/treatment	Phase
HIV-1	Drug: DRV 800 mg + COBI 150 mg + FTC 200 mg + TAF 10 mg FDC	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 109 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Single-arm, Open-label Study to Evaluate the Efficacy and Safety of Darunavir/ Cobicistat/ Emtricitabine/ Tenofovir Alafenamide (D/C/F/TAF) Once Daily Fixed-dose Combination (FDC) Regimen in Newly Diagnosed, Antiretroviral Treatment-naïve Human Immunodeficiency Virus Type 1 (HIV-1) Infected Subjects Receiving Care in a Test and Treat Model of Care
• Actual Study Start Date: July 31, 2017
• Actual Primary Completion Date: January 3, 2019
• Actual Study Completion Date: September 4, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: DRV 800 mg + COBI 150 mg + FTC 200 mg + TAF 10 mg FDC; Participants will receive oral tablet containing Darunavir 800 milligram (mg)/ Cobicistat 150 mg/ Emtricitabine 200 mg/ Tenofovir Alafenamide 10 mg (D/C/F/TAF) fixed-dose combination (FDC) once daily within 24 hours of the screening/baseline visit.	Drug: DRV 800 mg + COBI 150 mg + FTC 200 mg + TAF 10 mg FDC; Participants will receive oral tablet containing D 800 mg /C 150 mg /F 200 mg /TAF 10 mg FDC once daily within 24 hours of the screening/ baseline visit.

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants With Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) Less Than (<) 50 Copies Per Milliliter (Copies/mL) (Virologic Response) at Week 48 Defined by Food and Drug Administration (FDA) Snapshot Approach [ Time Frame: Week 48 ]
   Percentage of participants with a HIV-1 RNA < 50 copies per mL were assessed using FDA snapshot approach which defines a participant's virologic response status using only the viral load at the predefined time point within a window of time, along with study drug discontinuation status. If HIV RNA level is < 50 copies per mL at Week 48, it is considered as virologic success as per the snapshot approach.

Secondary Outcome Measures :

1. Change From Baseline in log10 HIV-1 RNA Viral Load (<50/200 Copies/mL) at Weeks 2, 4, 8, 12, 24, 36, and 48 [ Time Frame: Baseline, Weeks 2, 4, 8, 12, 24, 36, and 48 ]
   Change from baseline in log10 HIV-1 RNA viral load (<50/200 copies/mL) at Weeks 2, 4, 8, 12, 24, 36, and 48 were reported.
2. Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 [ Time Frame: Week 24 ]
   Percentage of participants with HIV-1 RNA < 50 copies/mL were reported.
3. Change From Baseline in Cluster of Differentiation 4 (CD4+) Cell Count at Weeks 12, 24 and 48 [ Time Frame: Baseline, Weeks 12, 24 and 48 ]
   The immunologic change was determined by changes in Cluster of CD4+ cell count. Change from baseline in CD4+ cell count at Weeks 12, 24 and 48 were assessed.
4. Number of Participants That Required Discontinuation After Enrollment Based on Safety Stopping Rules [ Time Frame: Up to Week 48 ]
   Number of participants that required discontinuation after enrollment based on safety stopping rules were reported. Stopping rules include the following reasons: a). Estimated glomerular filtration rate (eGFR) according to the Modification of Diet in Renal Disease (MDRD) formula < 50 milliliter per minute (mL/min) b). Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than or equal to (>=) 2.5*upper limit of normal (ULN); c). Serum lipase >=1.5*ULN; d). Positive serum human chorionic gonadotropin pregnancy test (beta-hCG) for women of childbearing potential; e). Laboratory results that the investigator believes should result in discontinuation of study medication; f). Participants identified with active hepatitis C virus (HCV) infection that in the opinion of the investigator requires HCV treatment immediately or expected to be needed during the course of the study with agents not compatible with D/C/F/TAF FDC.
5. Percentage of Participants Discontinuing Therapy Due to Adverse Events (AEs) [ Time Frame: Up to Week 48 ]
   Percentage of participants discontinuing therapy due to AEs were reported. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
6. Percentage of Participants Experiencing Grade 3 and 4 Adverse Events [ Time Frame: Up to Week 48 ]
   AE is any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Events with Grade 3 or higher (3=Severe; 4=life-threatening; 5=fatal) are events that significantly interrupt usual daily activity, require systemic drug therapy/other treatment and are, in many situations, considered unacceptable or intolerable events.
7. Percentage of Participants Experiencing Grade 3 and 4 Laboratory Abnormalities [ Time Frame: Up to Week 48 ]
   Percentage of participants experiencing grade 3 and 4 laboratory abnormalities was assessed by Division of Acquired Immunodeficiency Syndrome (DAIDS) Adverse Event (AE) Grading Table. Abnormal laboratory values with Grade 3 or higher (3=Severe; 4=potentially life-threatening) signifies an interruption of usual daily activity, requiring systemic drug therapy/other treatment and are, in many situations, considered unacceptable or intolerable.
8. Percentage of Participants Meeting Resistance Stopping Rules, Requiring Discontinuation of Study Treatment Due to Baseline Resistance Findings [ Time Frame: Up to Day 35 ]
   Percentage of participants meeting resistance stopping rules, requiring discontinuation of study treatment due to baseline resistance findings were reported. Investigator reviewed antiretroviral screening/baseline resistance data at Week 4, depending on availability of screening/baseline HIV genotypic drug resistance testing results from central laboratory. Participants who do not show full sensitivity to all drugs in the fixed-dose combination (FDC) study regimen according to the susceptibility assessment in the Genosure Prime report will be contacted to return to study site for early study treatment discontinuation (ESTD). Participants with identified resistance to lamivudine/Emtricitabine, attributed to the presence of the M184I/V mutation alone will be permitted to remain in the study.
9. Percentage of Participants With Baseline Protease (PI), Reverse Transcriptase (RT) and Integrase (INI)-Resistance-associated Mutation (RAMs) [ Time Frame: Baseline (Day 1) ]
   Percentage of Participants with resistance-associated mutations present at baseline were reported and included mutations in the domain of PR, RT (including nucleoside reverse transcriptase inhibitor [NRTIs] and non-nucleoside/nucleotide reverse transcriptase inhibitor [NNRTIs]), INI, RAMs as determined by the GenoSure Prime assay. Genotypes were not available for 7 participants due to failed amplification of viral deoxyribo nucleic acid (DNA) (that is, low viral load (VL) [<500 copies/mL], reduced viral fitness, compromised sample collection/handling, primer incompatibility).
10. Percentage of Participants With Protocol-defined Virologic Failure (PDVF) at Week 24 and 48 [ Time Frame: Week 24 and 48 ]
    Virologic failure is defined as: a) Virologic Nonresponse: HIV-1 RNA <1 log10 reduction from baseline, and HIV-1 RNA >= 400 copies/mL at the Week 12 visit, subsequently confirmed at an unscheduled visit conducted within 2 to 4 weeks after Week 12. b) Virologic Rebound: At any visit, after achieving confirmed consecutive HIV-1 RNA <50 copies/mL, a rebound in HIV 1 RNA to >= 50 copies/mL, which is subsequently confirmed at a scheduled or unscheduled visit conducted within 2 to 4 weeks of the HIV-1 RNA result; or At any visit, a >1 log10 increase in HIV-1 RNA from the nadir, which is subsequently confirmed at the following scheduled or unscheduled visit conducted within 2 to 4 weeks of the HIV-1 RNA result.
11. Percentage of Participants Developing Resistance-associated Mutation (RAMs) and Loss of Phenotypic Susceptibility, Upon Meeting Protocol-defined Virologic Failure (PDVF) [ Time Frame: Up to Week 48 ]
    Percentage of participants developing RAMs and loss of phenotypic susceptibility, upon meeting PDVF were reported. Virologic failure is defined as: a) Virologic Nonresponse: HIV-1 RNA <1 log10 reduction from baseline, and HIV-1 RNA greater than or equal to (>=) 400 copies/mL at the Week 12 visit, subsequently confirmed at an unscheduled visit conducted within 2 to 4 weeks after Week 12. b) Virologic Rebound: At any visit, after achieving confirmed consecutive HIV-1 RNA <50 copies/mL, a rebound in HIV 1 RNA to >= 50 copies/mL, which is subsequently confirmed at a scheduled or unscheduled visit conducted within 2 to 4 weeks of the HIV-1 RNA result; or At any visit, a >1 log10 increase in HIV-1 RNA from the nadir, which is subsequently confirmed at the following scheduled or unscheduled visit conducted within 2 to 4 weeks of the HIV-1 RNA result.
12. Percentage of Participants Lost-to-Follow-up Throughout the 48 Weeks of Treatment [ Time Frame: Up to Week 48 ]
    Percentage of participants lost-to-follow-up throughout the 48 Weeks of treatment were reported.
13. Percentage of Participants With Retention in Care Completed and With Documented Clinical Visit [ Time Frame: Up to Week 48 ]
    Percentage of participants with retention in care completed and with documented clinical visit (within 90 days of discontinuation) were reported.
14. Percentage of Participants With Treatment Adherence >95% Based on Pill Count at Weeks 4, 8, 12, 24, 36, and 48 [ Time Frame: Weeks 4, 8, 12, 24, 36, and 48 ]
    Percentage of participants with treatment adherence >95% based on pill count at Weeks 4, 8, 12, 24, 36, and 48 were reported. Treatment adherence was defined as having a treatment adherence of greater than (>) 95 percent (%) by pill count.
15. Percentage of Participants With 100% Treatment Adherence Based on Participants Self-Report, Using a 4-Day Recall at Weeks 4, 8, 12, 24, 36, and 48 [ Time Frame: Weeks 4, 8, 12, 24, 36, and 48 ]
    Percentage of participants with 100 % adherence based on participants self-report, using a 4-Day recall at Weeks 4, 8, 12, 24, 36, and 48 was reported.
16. Mean Total Scores for the HIV-Treatment Satisfaction Questionnaire (HIVTSQs) at Weeks 4, 24, and 48 [ Time Frame: Weeks 4, 24, and 48 ]
    The HIV treatment satisfaction questionnaire (HIVTSQ) is based on a 10-item self-reported scale that measures overall satisfaction with treatment. The HIVTSQ items are summed up to produce a treatment satisfaction score (0 to 60) and an individual satisfaction rating for each item (0 to 6). The higher the score, the greater the treatment satisfaction.
17. Number of Participants With Hospitalizations [ Time Frame: Up to Week 48 ]
    Number of participants with hospitalizations (overnight) was reported.
18. Duration of Hospitalizations [ Time Frame: Up to Week 48 ]
    Duration of hospitalizations in days was reported for those participants hospitalized during the course of the study. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this OM.
19. Number of Participants With Outpatient Visits [ Time Frame: Up to Week 48 ]
    Number of participants with outpatient visits (in addition to study visits, including General practitioner visit, Specialist visit, Nurse practitioner visit, Physician assistant visit, Home healthcare nurse visit and Other visit) was reported.
20. Number of Participants With Emergency Room Visits [ Time Frame: Up to Week 48 ]
    Number of participants with emergency room visits was reported.
21. Median Medical Costs of Care ((United States of America [USA] Dollars) Based on Healthcare Resource Utilization [HRU]) [ Time Frame: Up to Week 48 ]
    Median medical costs of care (United States of America [USA] dollars) based on healthcare resource utilization [HRU]) were reported. The cost of care specified for overnight hospitalization, hospital day care ward (without overnight), emergency room visit, general practitioner visit, specialist visit, nurse practitioner visit, physician assistant visit and Other visit.
22. Percentage of Participants Discontinuing Therapy Due to Adverse Events (AEs) Through Week 96 [ Time Frame: Up to Week 96 ]
    Percentage of participants discontinuing therapy due to AEs were reported. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
23. Percentage of Participants Experiencing Grade 3 and 4 Adverse Events Through Week 96 [ Time Frame: Up to Week 96 ]
    AE is any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Events with Grade 3 or higher (3=Severe; 4=life-threatening; 5=fatal) are events that significantly interrupt usual daily activity, require systemic drug therapy/other treatment and are, in many situations, considered unacceptable or intolerable events.
24. Percentage of Participants Experiencing Grade 3 and 4 Laboratory Abnormalities Through Week 96 [ Time Frame: Up to Week 96 ]
    Percentage of participants experiencing grade 3 and 4 laboratory abnormalities were assessed by Division of Acquired Immunodeficiency Syndrome (DAIDS) Adverse Event (AE) Grading Table. Abnormal laboratory values with Grade 3 or higher (3=Severe; 4=potentially life-threatening) signifies an interruption of usual daily activity, requiring systemic drug therapy/other treatment and are, in many situations, considered unacceptable or intolerable.
25. Percentage of Participants With Protocol-defined Virologic Failure (PDVF) at Week 72 and 96 [ Time Frame: Weeks 72 and 96 ]
    Virologic failure is defined as: a) Virologic Nonresponse: HIV-1 RNA <1 log10 reduction from baseline, and HIV-1 RNA >= 400 copies/mL at the Week 12 visit, subsequently confirmed at an unscheduled visit conducted within 2 to 4 weeks after Week 12. b) Virologic Rebound: At any visit, after achieving confirmed consecutive HIV-1 RNA <50 copies/mL, a rebound in HIV 1 RNA to >= 50 copies/mL, which is subsequently confirmed at a scheduled or unscheduled visit conducted within 2 to 4 weeks of the HIV-1 RNA result; or At any visit, a >1 log10 increase in HIV-1 RNA from the nadir, which is subsequently confirmed at the following scheduled or unscheduled visit conducted within 2 to 4 weeks of the HIV-1 RNA result.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Newly diagnosed with human immunodeficiency virus type 1 (HIV-1) evidenced by any of the following within 2 weeks of the screening/baseline visit: a) HIV Rapid Antibody positive; or b) HIV Immunoassay positive; or c) Positive p24 antigen and a HIV-1 ribonucleic acid (RNA) viral load greater than or equal to (>=) 5,000 copies per milliliter (copies/ mL); or d) Non-reactive HIV-1 antibody/antigen assays and HIV-1 RNA viral load (>=) 5,000 copies/mL. HIV-1 RNA viral load must be confirmed once within 1 week of initial HIV-1 RNA viral load test
• Antiretroviral treatment-naïve, except for the use of TRUVADA® for pre-exposure prophylaxis (PrEP)
• Must be able to swallow whole tablets
• A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for 90 days after receiving the last dose of study drug
• A woman of childbearing potential must have a negative urine pregnancy test at screening

Exclusion Criteria:

• Known active cryptococcal infection, active toxoplasmic encephalitis, Mycobacterium tuberculosis infection, or another acquired immunodeficiency syndrome (AIDS) -defining condition that in the judgement of the investigator would increase the risk of morbidity or mortality
• Known history of clinically relevant hepatic disease or hepatitis that in the investigator's judgement is not compatible with Darunavir/ Cobicistat/ Emtricitabine/ Tenofovir Alafenamide (D/C/F/TAF FDC)
• Known history of cirrhosis as diagnosed based on local practices
• Known history of chronic ([>=] 3 months) renal insufficiency, defined as having an estimated glomerular filtration rate (eGFR) less than (<) 50 milliliter per minute (mL/min) according to the Modification of Diet in Renal Disease (MDRD) formula
• Pregnant, or breast-feeding, or planning to become pregnant while enrolled in this study or within 90 days after the last dose of study treatment

Contacts and Locations

Locations

United States, Arizona

Spectrum Medical Group

Phoenix, Arizona, United States, 85012

United States, California

The Office of Franco Felizarta, MD

Bakersfield, California, United States, 93301

Jeffrey Goodman Clinic - DBA Los Angeles Gay and Lesbian Center

Los Angeles, California, United States, 90028

United States, District of Columbia

Whitman Walker Health

Washington, District of Columbia, United States, 20009

United States, Florida

Midway Immunology and Research Center

Fort Pierce, Florida, United States, 34982

University of Miami

Miami, Florida, United States, 33136

Orlando Immunology Center

Orlando, Florida, United States, 32803

United States, Georgia

Chatham County Health Department

Savannah, Georgia, United States, 31401

United States, Illinois

The Ruth M. Rothstein CORE Center

Chicago, Illinois, United States, 60612

United States, New Jersey

Saint Michael's Medical Center - Infectious Disease

Newark, New Jersey, United States, 07102

United States, New Mexico

Southwest CARE Center

Albuquerque, New Mexico, United States, 87109

Southwest CARE Center

Santa Fe, New Mexico, United States, 87505

United States, Texas

North Texas Infectious Diseases Consultants

Dallas, Texas, United States, 75246

Texas Centers for Infectious Disease Associates

Fort Worth, Texas, United States, 76104

Therapeutic Concepts - Donald R Watkins Foundation

Houston, Texas, United States, 77004

Gordon Crofoot, MD

Houston, Texas, United States, 77098

Sponsors and Collaborators

Janssen Scientific Affairs, LLC

Investigators

• Study Director: Janssen Scientific Affairs, LLC Clinical Trial; Janssen Scientific Affairs, LLC

  Study Documents (Full-Text)

Documents provided by Janssen Scientific Affairs, LLC:

Study Protocol  [PDF] November 16, 2017

Statistical Analysis Plan  [PDF] September 18, 2019

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Dunn K, Rogers R, Simonson RB, Luo D, Sheng S, Kassam PT, Seyedkazemi S, Hardy H. Rapid initiation of darunavir/cobicistat/emtricitabine/tenofovir alafenamide in acute and early HIV-1 infection: a DIAMOND subgroup analysis. HIV Res Clin Pract. 2021 Apr;22(2):55-61. doi: 10.1080/25787489.2021.1915652. Epub 2021 May 17.

Huhn GD, Crofoot G, Ramgopal M, Gathe J, Bolan R, Luo D, Simonson RB, Nettles RE, Benson C, Dunn K. Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in a Rapid-Initiation Model of Care for Human Immunodeficiency Virus Type 1 Infection: Primary Analysis of the DIAMOND Study. Clin Infect Dis. 2020 Dec 15;71(12):3110-3117. doi: 10.1093/cid/ciz1213.

• Responsible Party: Janssen Scientific Affairs, LLC
• ClinicalTrials.gov Identifier: NCT03227861
• Other Study ID Numbers: CR108345; TMC114FD2HTX3002 ( Other Identifier: Janssen Scientific Affairs, LLC )
• First Posted: July 24, 2017
• Results First Posted: January 7, 2020
• Last Update Posted: September 25, 2020
• Last Verified: September 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Immunologic Deficiency Syndromes; Acquired Immunodeficiency Syndrome; HIV Infections; Immune System Diseases; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases